A Randomized Controlled Trial of a Fermented Soy Beverage Among Patients with Localized Prostate Cancer Prior to Radical Prostatectomy

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Lokeshwar, Ather Ali, Theresa R. Weiss, Jesse Reynolds, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3240223/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 May, 2024 Read the published version in BMC Urology → Version 1 posted 4 You are reading this latest preprint version Abstract Background Fermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy. Methods We conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2–5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata. Results We randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline – end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05). Conclusions Short exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved. Trial Registration ClinicalTrials.gov Identifier: NCT03532308, May 9, 2018 prostate cancer PSA fermented soy randomized controlled trial Figures Figure 1 Introduction Prostate cancer (PCa) is the most commonly diagnosed cancer in males and the second most common cause of cancer related deaths among men in the United States( 1 ). The burden from prostate cancer is substantial when appreciated on a global scale. Although often localized and slow-growing, treatments and disease monitoring are associated with significant toxicity, economic expenditure, and enduring risks of disease progression and cancer mortality. Given the protracted, yet potentially fatal, natural history of the disease, there is growing interest in low-risk interventions, particularly diet and lifestyle, in the tertiary prevention of prostate cancer. In particular, plant-based diets have been associated with numerous prostate cancer related outcomes including incidence, progression and mortality.( 2 ) For example, in population-based studies, overall plant-based consumption was associated with lower risk of fatal prostate cancer, and in men < 65 was plant-based consumption was associated with lower risk of advanced, lethal, and fatal prostate cancer.( 3 ) There is a large amount of data regarding the association of soy and cancer( 4 , 5 ). The epidemiological data is mostly supportive with a reduced risk of breast cancer in Chinese populations with high dietary soy, and this has been confirmed in populations in the United States with relatively lower soy consumption( 6 , 7 ). ZhenHua 851 or (Q-CAN® Plus or “QC”) is a fermented soy food product that contains medium chain triglycerides, ketones and soy isoflavones, and is available in commercial form. Uncontrolled studies and case reports support QC benefits in cancer progression and changes in activation markers in humans’ immune cells including changes in expression of CD3, CD4, and CD8 markers, as well increased NK cell activity ( 8 , 9 ). Specifically, these reports associate consumption of QC with reduced prostate specific antigen (PSA) velocity in men with PCa( 10 ). Patients express a strong interest in diet and lifestyle interventions in prostate cancer however there is a dearth of high-quality information available to inform clinical recommendations. Much of the available evidence addressing diet and lifestyle in prostate cancer has come in the form of anecdotal, or observational studies prone to methodological biases associated with unmeasured confounding and varied exposure. Therefore, the purpose of this study is to assess the efficacy of QC fermented soy on localized PCa prior to radical prostatectomy (RP) in a controlled trial setting. Methods Trial design and oversight We performed a parallel group, double blind, randomized, clinical trial among patients with clinically localized prostate cancer who had elected initial treatment with RP (Fig. 1 ). The investigational product was Q-CAN® Plus (“QC”), a fermented soybean-derived phytochemical food supplement in liquid form( 11 ). In order to validate the Certificate of Analysis, the soy test agent (QC) underwent quarantine and independent third-party laboratory analysis (product characterization). QC is a commercially available beverage. The product’s primary constituents are the isoflavones genistin and daidzin (and respective metabolites of genistein and daidzein). Study participants were randomized to one of two arms: to receive either Daily QC or placebo. Patients in the intervention arm received Daily QC (QCAN fermented soy) as two 12.5 packets/day approximately or 1 ounce/day between the time of enrollment and RP. Patients in the control arm received daily matched dose placebo. These were taken at time of enrollment to RP (between 4 and 10 weeks prior to surgery). Participants were considered to have completed the study if they had completed all study visits. Study visits included an initial screening and baseline visit, a second visit for assignment of intervention, weekly phone calls thereafter to asses safety and adherence/dosing and a final assessment visit. To be eligible for participation, we required that patients had histologically verified PCa at any stage, were ≥ 18 years of age and scheduled to be treated by RP within 4 to 10 weeks from screening and enrollment. Patients were excluded if they had previous (within 6 months of enrollment) or concurrent hormonal therapy or chemotherapy; specifically, treatment with 5-alpha reductase inhibitors (finasteride and dutasteride), history of hormone dependent malignancies, concomitant thyroid disease or currently taking thyroid hormone replacement medication, current high-dose soy consumption, micronutrient, or herbal supplements, on soy or vegetarian nutrition, or any other extreme dietary habits, currently taking oral anticoagulants or parenteral injection of low molecular weight heparin (enoxaparin), current or past history of any liver or pancreas disease, history of hypersensitivity to soy-containing products or malabsorption conditions. The primary study endpoint was change in serum PSA defined as the difference between baseline PSA value and PSA value at the time of RP. Baseline was defined as the date that an eligible participant enrolled in the trial. The secondary endpoints were changes in other clinical and pathologic endpoints including prognostic Gleason Grade Group, stage, margin status, overall Cancer of the Prostate Risk Assessment (CAPRA) score, lipid levels, testosterone, and health related quality of life (FACT-P score). The target sample size per design was 72. All patients provided written informed consent prior to administering any study procedures. Interim analysis and monitoring were performed by the principle investigators and presented and reviewed by the independent Data Safety Monitoring Board. This trial was approved by the Yale University institutional review board. Statistical Analysis The intent-to-treat (ITT) efficacy analysis of endpoints included data from all randomized study participants. Safety was analyzed using data from all study participants who received at least one dose of QC. The analysis of safety included all events that occurred from the time of the first dose until the participant’s final assessment, just prior to RP. Final assessment of primary outcome, PSA as well as change of PSA utilized data from all participants who had end of study information available and complete laboratory analysis. A two-sided Type I error of 0.05 was used as the level of statistical significance. The ITT analysis of the primary outcome was conducted using a repeated measures analysis or linear mixed model analysis using the stratification variable of baseline CAPRA risk. A secondary analysis the of primary outcome was performed using a generalized linear model adjusting for baseline PSA value. Continuous secondary outcomes were analyzed using linear mixed models to assess mean changes (pre- to post-surgery). The Gleason score and quality of life (FACT-P), both ordinal variables, were analyzed using a Wilcoxon Signed Rank test. Degree of tumor focality was assessed with the chi-square method. Results Patients From August 2, 2018 to December 4, 2019, a total of 19 eligible patients were enrolled and randomized; 10 were assigned to the QC group and 9 were assigned to the placebo group. Baseline characteristics and demographics were well balanced between the two groups (Table 1 ). The median age of patients at time of enrollment in the QC cohort was 60.5 years and 60 years in the placebo cohort. At the time of final analysis, 16 patients were assessed for final measurement of primary outcome. Per CAPRA risk score, 9 (56.2%) patients were considered low and intermediate risk, and 7 (43.8%) were considered high CAPRA risk. Due to low enrollment, and after consultation and recommendation by the DSMB, an interim analysis was conducted after 19 participants had been enrolled, which suggested no statistically significant differences in the primary endpoint. Therefore, the investigators and sponsors elected to terminate the study early. Table 1 Baseline Characteristics of included patients Characteristic Daily QC (n = 10) Placebo (n = 9) Total (n = 19) Difference (95% CI) Age at Study Mean (95% CL) 60.60 (55.66, 65.54) 62.89 (57.95, 67.83) 61.68 (58.50, 64.87) 2.28 (-8.77, 4.19) Mean (SD) 60.60 (6.90) 62.89 (6.43) 61.68 (6.60) Median (IQR) 60.5 (58.0–66.0) 60.0 (58.0–69.0) 60.0 (58.0–69.0) Education, number of years : Mean (95% CL) 12.60 (11.42, 13.78) 14.11 (12.76, 15.47) 13.32 (12.44, 14.20) 1.51 (-3.16, 0.14) Mean (SD) 12.60 (1.65) 14.11 (1.76) 13.32 (1.83) Median (IQR) 12.0 (12.0–14.0) 14.0 (12.0–16.0) 12.0 (12.0–15.0) Gender Male 10 (100.00%) 9 (100.00%) 19 (100.00%) -- Race self-identity Black or African American 2 (20.00%) 2 (22.22%) 4 (21.05%) − 2% (-45%, 49%) White 8 (80.00%) 7 (77.78%) 15 (78.95%) 2% (-49%, 45%) Ethnicity Hispanic or Latino 1 (10.00%) 0 (00.00%) 1 (5.26%) 10% (-39%, 19%) Non-Hispanic 9 (90.00%) 9 (100.00%) 18 (94.74%) -10% (-19%, 39%) Site Lawrence & Memorial Hospital 5 (50.00%) 6 (66.67%) 11 (57.89%) -16% (-37%, 70%) Yale University 5 (50.00%) 3 (33.33%) 8 (42.11%) 17% (-70%, 37%) Marital status : Married or Cohabiting 7 (70.00%) 8 (88.89%) 15 (78.95%) -19% (-26%, 64%) Not married/cohabitating 3 (30.00%) 1 (11.11%) 2 (10.53%) 19% (-64%, 26%) Change in serum PSA The difference in mean baseline PSA of the QC and Placebo groups was not statistically significant (8.98, 95% CI: 6.07–11.89 versus 8.66, 95% CI: 6.58–10.74, respectively). At the end of the study there was no statistically significant difference in PSA in the QC cohort compared to the placebo (8.02, 95% CI: 4.96–11.09 versus 9.53, 95% CI: 6.73–12.33) respectively). In terms of the difference between baseline and end of study PSA, there was no statistically significant difference between QC cohort and placebo (0.85, 95% CI: -1.01–2.71 versus − 0.13, 95% CI: -1.46–1.19 respectively) (Table 2 a). When stratified by CAPRA risk in the QC cohort compared to placebo, there was no statistically significant difference in baseline PSA, end of study PSA or PSA change from baseline to end of study (p > 0.05) (Table 2 b). Table 2 A. Primary Outcome Bivariate Analysis: PSA, B. Primary Outcome Bivariate Analysis: PSA, Stratified by CAPRA Risk A Treatment QC Placebo Total P Value Baseline N (N Missing) 10 (0) 9 (0) 19 (0) Mean (SD) 8.98 (4.07) 8.66 (2.71) 8.83 (3.40) 0.85 Mean (95% CL) 8.98 (6.07–11.89) 8.66 (6.58–10.74) 8.83 (7.19–10.47) 0.85 Median (Range) 9.3 (2.3–15.3) 8.2 (5.1–12.7) 8.7 (2.3–15.3) 0.9 End of Study N (N Missing) 9 (1) 7 (2) 16 (3) Mean (SD) 8.02 (3.99) 9.53 (3.03) 8.68 (3.57) 0.42 Mean (95% CL) 8.02 (4.96–11.09) 9.53 (6.73–12.33) 8.68 (6.78–10.59) 0.42 Median (Range) 8.0 (1.7–15.9) 10.8 (4.5–12.7) 8.5 (1.7–15.9) 0.34 Difference (Baseline – End of Study) N (N Missing) 9 (1) 7 (2) 16 (3) Mean (SD) 0.85 (2.42) -0.13 (1.43) 0.42 (2.05) 0.36 Mean (95% CL) 0.85 (-1.01–2.71) -0.13 (-1.46–1.19) 0.42 (-0.67–1.51) 0.36 Median (Range) 0.6 (-2.8–5.2) -0.1 (-2.5–2.1) 0.4 (-2.8–5.2) 0.4 B. Treatment QC Placebo Total P Value Low Risk Baseline N (N Missing) 5 (0) 5 (0) 10 (0) Mean (SD) 6.26 (3.34) 8.08 (2.72) 7.17 (3.03) 0.37 Mean (95% CL) 6.26 (2.11 – 10.41) 8.08 (4.70 – 11.45) 7.17 (5.00 – 9.33) 0.37 Median (Range) 5.4 (2.3 – 10.6) 7.0 (5.8 – 12.7) 6.8 (2.3 – 12.7) 0.4 End of Study N (N Missing) 5 (0) 4 (1) 9 (1) Mean (SD) 6.50 (3.63) 8.07 (3.30) 7.20 (3.37) 0.53 Mean (95% CL) 6.50 (2.00 – 11.01) 8.07 (2.82 – 13.31) 7.20 (4.61 – 9.79) 0.53 Median (Range) 7.2 (1.7 – 10.1) 7.7 (4.5 – 12.4) 7.2 (1.7 – 12.4) 0.71 Difference (Baseline – End of Study) N (N Missing) 5 (0) 4 (1) 9 (1) Mean (SD) -0.24 (1.70) 0.27 (1.38) -0.02 (1.49) 0.64 Mean (95% CL) -0.24 (-2.35 – 1.87) 0.27 (-1.93 – 2.47) -0.02 (-1.16 – 1.13) 0.64 Median (Range) 0.5 (-2.8 – 1.5) 0.1 (-1.2 – 2.1) 0.3 (-2.8 – 2.1) 1 High Risk Baseline N (N Missing) 5 (0) 4 (0) 9 (0) Mean (SD) 11.69 (2.76) 9.40 (2.90) 10.67 (2.90) 0.26 Mean (95% CL) 11.69 (8.27 – 15.12) 9.40 (4.78 – 14.01) 10.67 (8.44 – 12.90) 0.26 Median (Range) 10.8 (8.6 – 15.3) 10.5 (5.1 – 11.5) 10.7 (5.1 – 15.3) 0.54 End of Study N (N Missing) 4 (1) 3 (1) 7 (2) Mean (SD) 9.92 (4.03) 11.49 (1.07) 10.59 (3.04) 0.55 Mean (95% CL) 9.92 (3.51 – 16.34) 11.49 (8.82 – 14.16) 10.59 (7.79 – 13.40) 0.55 Median (Range) 8.3 (7.2 – 15.9) 10.9 (10.8 – 12.7) 10.8 (7.2 – 15.9) 0.38 Difference (Baseline – End of Study) N (N Missing) 4 (1) 3 (1) 7 (2) Mean (SD) 2.21 (2.71) -0.67 (1.59) 0.97 (2.62) 0.17 Mean (95% CL) 2.21 (-2.10 – 6.51) -0.67 (-4.61 – 3.27) 0.97 (-1.45 – 3.40) 0.17 Median (Range) 2.1 (-0.6 – 5.2) -0.1 (-2.5 – 0.6) 0.6 (-2.5 – 5.2) 0.22 Secondary Outcomes There was no statistically significant difference in Gleason score, clinical stage, surgical margins, percent of biopsy cores involved in cancer, extracapsular extension, lymph node invasion, seminal vesicle invasion or CAPRA score between the QC and placebo groups. In addition, there were no statistically significant differences between the QC arm and placebo arm in end-of-study or change in lipids, free and total testosterone (p > 0.05). In the evaluation of quality-of-life measures, there was no significant difference in change of FACT-P score from baseline to end of study between the QC arm and the placebo arm (diff = 9.38, 95% CI: -1.22–19.98, p > 0.05). Furthermore, there was no significant difference in change of physical well-being, social well-being, emotional well-being, functional well-being, or PWB, SWB, EWB, FWB or Prostate cancer subscale, sub scores. Safety A total of 4 adverse events in 3 patients in the QC arm and 1 adverse event in the placebo arm were reported in the study (Table 3 ). There was one serious adverse event (SAE) in the QC group requiring hospitalization: a participant presented with an enlarging aortic aneurysm and pneumonia during the trial period, but the SAE was deemed unrelated to QC administration. There were no serious adverse events that resulted in trial discontinuation in either cohort. There were no deaths during the trial period. Table 3: Adverse Events Event name QC (n events, n patients) Placebo (n events, n patients) Total (n events, n patients) Rash (1, 1) (0, 0) (1, 1) Aortic Aneurysm and Pneumonia * (1, 1) (0, 0) (1, 1) Nausea / Dizzyness (1, 1) (0, 0) (1, 1) Atrial Fibrillation (1, 1) (1, 1) (2, 2) Number of unique participants with AE (4, 3) (1, 1) (5, 4) AE led to study discontinuation 0 0 0 Key: * denotes SAE Discussion We performed a double blind, randomized, clinical trial to evaluate the effect of a soy product, QC, on PSA in patients with PCa prior to RP. We found no statistically significant difference in PSA changes in patients treated with QC compared to Placebo. We also found no difference in surgical specimens (including Gleason score, surgical margins, clinical stage, extracapsular extension, lymph node or semivesical invasion) or laboratory parameters (free, total and bioavailable testosterone, amylase, CRP, C-reactive protein, HDL, LDL, Lipase, ESR, TSH, triglycerides) in patients treated with QC. Furthermore, we found no changes in quality of life for patients treated with QC compared to placebo. There were no serious adverse events directly attributed to QC during the trial period. To our knowledge, this is the first randomized control trial to evaluate a fermented soy product’s effect on PSA and surgical parameters in patients with PCa undergoing RP. Even though the study was terminated prematurely due to inability to recruit, and thus did not achieve the design power, contributes to a growing body of literature aimed toward evaluating low-toxicity interventions in the tertiary prevention of morbidity and mortality in patients with PCa. Soy isoflavones have been previously investigated for their relationship with PCa. In terms of risk of PCa, a systematic review and metanalysis summarized the results of 30 studies investigating soy product intake and PCa risk. The metanalysis found a significant association of soy intake with reduced risk of PCa (Total soy food (p < 0.001), genistein (p = 0.008), daidzein (p = 0.018), and unfermented soy food (p < 0.001))( 12 ). In patients with PCa, a recent systematic review assessed the role of genistein in PCa parameters, where the effect of genistein supplementation was investigated in two studies( 13 ). Lazarevic et al. investigated the effect of 30 mg of genistein daily for three to six weeks prior to RP compared to placebo in a randomized phase 2 clinical trial of 54 men with localized PCa. Compared to placebo, patients treated with genistein had statistically insignificant change in PSA (p = 0.051), however they had a significant difference in cellular response (p = 0.033), and cell proliferation (p < 0.001).( 14 ) However, this trial was evaluated and was found to have a high or unclear risk of bias on 4 out of 7 criteria but low risk of bias for sequence generation and blinding as well as selective outcome reporting. In contrast, in a relatively low risk of bias trial, randomization of 60 mg of genistein daily versus placebo for 12 weeks in men enrolled in watchful waiting, yielded no impact on mean change in PSA( 15 ). Similar to the findings of our clinical trial on fermented soy, Hamilton-Reeves et al. performed a double-blind, randomized, placebo-controlled trial to examine the effects of soy isoflavone capsules in patients with localized PCa for 6 weeks prior to RP. There was no statistically significant difference in change in PSA, testosterone, estrogen, or total cholesterol( 16 ). Q-CAN has been shown to reduces viability and increase apoptosis of cancer cells in a fermentation, concentration and time dependent manner. This suggests that fermentation of soy results in the production of metabolites that can reduce cancer cell viability, and induce cellular apoptosis( 17 ). Interestingly it was shown that these actions occurred independent of genistein content. An important distinction of our study from the current available literature on PCa and soy, is that our trial investigated the fermented soy product QC specifically in a randomized control setting. Strengths of our study include the strict inclusion criteria and its randomized prospective nature. Additionally, unlike prior trials on soy and PCa, our study captured PSA results, laboratory values, surgical parameters, and quality of life measures. There are several important limitations to note. Most significantly, this trial included a small sample size due to early terminiation and failed to achieve the protocol determined sample size. Therefore, adequate statistical power was not reached to assess the prespecified study endpoints. As additional considerations we did not account for longer-term outcomes or data regarding continued patient exposure to QC post-treatment. Additionally, PSA is a surrogate measure which may not adequately represent cancer risk or response and may fail to identify a variety of antitumor effects. In addition, the length of the exposure was relatively short (a minimum of 2 weeks), which may also be inadequate to lead to measurable differences in clinical parameters. To account for these limitations, further trials should be cognizant of potential sample size limitations, considerations of exposure length, and should incorporate a wider range of clinical and biological endpoints. Conclusion A short exposure to a fermented soy beverage among patients with localized prostate cancer was not associated with changes in PSA levels or other prostate cancer characteristics, including grade and stage or serum testosterone. As a consequence of early termination, study power, per design, was not achieved. Declarations Consent for publication: N/A Availability of data and materials: Data that support the findings of this study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate: All methods were carried out in accordance with relevant guidelines and regulations. All patients provided written informed consent prior to administering any study procedures. Interim analysis and monitoring were performed by the principle investigators and presented and reviewed by the independent Data Safety Monitoring Board. This trial was approved by the Yale University institutional review board, Protocol Number: 2000020868 Competing interests: None Funding: BESO Biologic Research, Inc. Author contributions: Trial Design: MSL, AA, Secured Funding: MSL, AA, Statistics: SDL, TF, TW, JR, WZM, TCK, MSL, Patient recruitment: BMS, JB, JR, MSL Wrote Manuscript: SDL, MSL, Manuscript Review: all authors Acknowledgments: NA Author’s information: Dr. Michael Leapman Email: [email protected] 203-785-2140 800 Howard Ave Fl 3, New Haven, CT 06519 Department of Urology, Yale School of Medicine, New Haven CT References Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(1):7-33. Epub 20220112. doi: 10.3322/caac.21708. PubMed PMID: 35020204. Gupta N, Patel HD, Taylor J, Borin JF, Jacobsohn K, Kenfield SA, et al. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. Prostate Cancer Prostatic Dis. 2022;25(3):444-52. Epub 20220705. doi: 10.1038/s41391-022-00553-2. PubMed PMID: 35790788. Loeb S, Fu BC, Bauer SR, Pernar CH, Chan JM, Van Blarigan EL, et al. Association of plant-based diet index with prostate cancer risk. Am J Clin Nutr. 2022;115(3):662-70. doi: 10.1093/ajcn/nqab365. PubMed PMID: 34791008; PubMed Central PMCID: PMC8895206. Fraser GE, Jaceldo-Siegl K, Orlich M, Mashchak A, Sirirat R, Knutsen S. Dairy, soy, and risk of breast cancer: those confounded milks. Int J Epidemiol. 2020. Epub 2020/02/26. doi: 10.1093/ije/dyaa007. PubMed PMID: 32095830. Kucuk O. Soy foods, isoflavones, and breast cancer. Cancer. 2017;123(11):1901-3. Epub 2017/03/07. doi: 10.1002/cncr.30614. PubMed PMID: 28263364. Wu YC, Zheng D, Sun JJ, Zou ZK, Ma ZL. Meta-analysis of studies on breast cancer risk and diet in Chinese women. Int J Clin Exp Med. 2015;8(1):73-85. Epub 2015/03/19. PubMed PMID: 25784976; PubMed Central PMCID: PMC4358431. Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, et al. Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer. 2017;123(11):2070-9. Epub 2017/03/07. doi: 10.1002/cncr.30615. PubMed PMID: 28263368; PubMed Central PMCID: PMC5444962. Ouyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, et al. Fermented Soy Drink (Q-CAN® PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutr Cancer. 2022:1-10. Epub 20220523. doi: 10.1080/01635581.2022.2077385. PubMed PMID: 35603899. Su SJ, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, et al. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol. 2005;69(2):307-18. Epub 20041119. doi: 10.1016/j.bcp.2004.09.025. PubMed PMID: 15627483. Battaglia A, Devos G, Boeckx G, Goeman L, Tosco L, de Meerleer G, et al. Prostate-Specific Antigen Modulatory Effect of a Fermented Soy Supplement for Patients with an Elevated Risk of Prostate Cancer: a Non-Randomized, Retrospective Observational Registration. Curr Urol. 2020;14(3):142-9. Epub 20201013. doi: 10.1159/000499246. PubMed PMID: 33224007; PubMed Central PMCID: PMC7659407. Mehal W, Secor E, Weiss T, Fields M, Leapman M, Ali A. Isoflavone Stability Quality Control Assessment of Q-CAN® Plus, a Novel Fermented Soy Beverage (P12-034-19). Current Developments in Nutrition. 2019;3(Supplement_1):nzz035. P12-4-19. Applegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. Nutrients. 2018;10(1). Epub 20180104. doi: 10.3390/nu10010040. PubMed PMID: 29300347; PubMed Central PMCID: PMC5793268. Hackshaw-McGeagh LE, Perry RE, Leach VA, Qandil S, Jeffreys M, Martin RM, et al. A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality. Cancer Causes Control. 2015;26(11):1521-50. Epub 20150909. doi: 10.1007/s10552-015-0659-4. PubMed PMID: 26354897; PubMed Central PMCID: PMC4596907. Lazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, et al. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutr Cancer. 2011;63(6):889-98. Epub 20110629. doi: 10.1080/01635581.2011.582221. PubMed PMID: 21714686. Kumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J, et al. The specific role of isoflavones in reducing prostate cancer risk. The Prostate. 2004;59(2):141-7. doi: 10.1002/pros.10362. PubMed PMID: 15042614. Hamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB, Kambhampati S, et al. Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial. PLoS One. 2013;8(7):e68331. Epub 20130712. doi: 10.1371/journal.pone.0068331. PubMed PMID: 23874588; PubMed Central PMCID: PMC3710024. Ouyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, et al. Fermented Soy Drink (Q-CAN(R) PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutr Cancer. 2022;74(10):3670-8. Epub 2022/05/24. doi: 10.1080/01635581.2022.2077385. PubMed PMID: 35603899. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 May, 2024 Read the published version in BMC Urology → Version 1 posted Editorial decision: Major revision 21 Aug, 2023 Editor assigned by journal 21 Aug, 2023 Submission checks completed at journal 10 Aug, 2023 First submitted to journal 06 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3240223","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":225389189,"identity":"fcdfc023-66fe-48ad-8498-11b0fb19a8c4","order_by":0,"name":"Soum D. Lokeshwar","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Soum","middleName":"D.","lastName":"Lokeshwar","suffix":""},{"id":225389190,"identity":"7449de5b-b929-4b7c-9c9b-32f1ba7a819d","order_by":1,"name":"Ather Ali","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ather","middleName":"","lastName":"Ali","suffix":""},{"id":225389191,"identity":"b521bc4d-a92f-44ed-8686-95f54ed5a0cb","order_by":2,"name":"Theresa R. Weiss","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Theresa","middleName":"R.","lastName":"Weiss","suffix":""},{"id":225389192,"identity":"0e5c0cf7-476f-4dbd-a918-4fa14d5d2bd2","order_by":3,"name":"Jesse Reynolds","email":"","orcid":"","institution":"Yale School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Jesse","middleName":"","lastName":"Reynolds","suffix":""},{"id":225389193,"identity":"b1da52ce-f7af-47e3-b9f0-7dc652001d26","order_by":4,"name":"Brian M. Shuch","email":"","orcid":"","institution":"David Geffen School of Medicine at UCLA","correspondingAuthor":false,"prefix":"","firstName":"Brian","middleName":"M.","lastName":"Shuch","suffix":""},{"id":225389194,"identity":"098955f5-137c-447d-9079-7661eaa53b96","order_by":5,"name":"Thomas Ferencz","email":"","orcid":"","institution":"Yale Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Ferencz","suffix":""},{"id":225389196,"identity":"ca05f1b9-2852-4823-b1f9-f092fc893d0d","order_by":6,"name":"Tassos C. Kyriakides","email":"","orcid":"","institution":"Yale School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Tassos","middleName":"C.","lastName":"Kyriakides","suffix":""},{"id":225389199,"identity":"9417e306-5437-4413-8121-0c649ec859c1","order_by":7,"name":"Wajahat Z. Mehal","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Wajahat","middleName":"Z.","lastName":"Mehal","suffix":""},{"id":225389202,"identity":"8f3bc820-6ba7-445e-bdaa-6ae7939c631c","order_by":8,"name":"Joseph Brito","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Brito","suffix":""},{"id":225389204,"identity":"2ab1c564-bbf8-4b48-8a5a-0fc190fe4b0d","order_by":9,"name":"Joseph Renzulli","email":"","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Renzulli","suffix":""},{"id":225389208,"identity":"e367d2c8-74f6-4c99-acae-0600f4d1dbd2","order_by":10,"name":"Michael S. Leapman","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABC0lEQVRIiWNgGAWjYDACZgY2IGnBwAflywGFGsDiBLRIgEkQMGZgYCSghQFNS2IDIS267czPHvyoAGphb3726EbNnfQNxw82PmCosE5swKHF7DCbuWHPGaAWnmPmxjnHnuVuOJPYbMBwJh2PFh42Cd42oBaJBDPpHLbDuRsOJLZJMLYdxqtF8u8/oBb559+kc/4dTjc4/7D9B+M//FqkeRtAtvCYSee2HU4wuJHYBgwBfFrYzKRljknwsPHklBvn9h02nHnjYbNEwrF0Y5xazh9+JvmmxkaOn/34tsc53w7L851PPvjhQ421LC4tMMDDwACNGoUDQCKBgHIYgGiRJ2T6KBgFo2AUjDgAACrPVvq0noK2AAAAAElFTkSuQmCC","orcid":"","institution":"Yale School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"S.","lastName":"Leapman","suffix":""}],"badges":[],"createdAt":"2023-08-07 00:59:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3240223/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3240223/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12894-024-01483-y","type":"published","date":"2024-05-03T19:57:26+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":41667901,"identity":"21a843ca-dca9-45d1-8165-bdf33bb48124","added_by":"auto","created_at":"2023-08-17 02:32:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":27174,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy Consort Diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3240223/v1/238dfae0592ba2dc71e6b0e9.png"},{"id":56042782,"identity":"e966e6a4-1e48-4881-b054-92f7a9394cc0","added_by":"auto","created_at":"2024-05-07 20:06:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":754908,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3240223/v1/333e97e2-0828-472d-9720-62dbe33dc199.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA Randomized Controlled Trial of a Fermented Soy Beverage Among Patients with Localized Prostate Cancer Prior to Radical Prostatectomy \u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eProstate cancer (PCa) is the most commonly diagnosed cancer in males and the second most common cause of cancer related deaths among men in the United States(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The burden from prostate cancer is substantial when appreciated on a global scale. Although often localized and slow-growing, treatments and disease monitoring are associated with significant toxicity, economic expenditure, and enduring risks of disease progression and cancer mortality. Given the protracted, yet potentially fatal, natural history of the disease, there is growing interest in low-risk interventions, particularly diet and lifestyle, in the tertiary prevention of prostate cancer. In particular, plant-based diets have been associated with numerous prostate cancer related outcomes including incidence, progression and mortality.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) For example, in population-based studies, overall plant-based consumption was associated with lower risk of fatal prostate cancer, and in men\u0026thinsp;\u0026lt;\u0026thinsp;65 was plant-based consumption was associated with lower risk of advanced, lethal, and fatal prostate cancer.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere is a large amount of data regarding the association of soy and cancer(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The epidemiological data is mostly supportive with a reduced risk of breast cancer in Chinese populations with high dietary soy, and this has been confirmed in populations in the United States with relatively lower soy consumption(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). ZhenHua 851 or (Q-CAN\u0026reg; Plus or \u0026ldquo;QC\u0026rdquo;) is a fermented soy food product that contains medium chain triglycerides, ketones and soy isoflavones, and is available in commercial form. Uncontrolled studies and case reports support QC benefits in cancer progression and changes in activation markers in humans\u0026rsquo; immune cells including changes in expression of CD3, CD4, and CD8 markers, as well increased NK cell activity (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Specifically, these reports associate consumption of QC with reduced prostate specific antigen (PSA) velocity in men with PCa(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatients express a strong interest in diet and lifestyle interventions in prostate cancer however there is a dearth of high-quality information available to inform clinical recommendations. Much of the available evidence addressing diet and lifestyle in prostate cancer has come in the form of anecdotal, or observational studies prone to methodological biases associated with unmeasured confounding and varied exposure. Therefore, the purpose of this study is to assess the efficacy of QC fermented soy on localized PCa prior to radical prostatectomy (RP) in a controlled trial setting.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTrial design and oversight\u003c/h2\u003e \u003cp\u003e We performed a parallel group, double blind, randomized, clinical trial among patients with clinically localized prostate cancer who had elected initial treatment with RP (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The investigational product was Q-CAN\u0026reg; Plus (\u0026ldquo;QC\u0026rdquo;), a fermented soybean-derived phytochemical food supplement in liquid form(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In order to validate the Certificate of Analysis, the soy test agent (QC) underwent quarantine and independent third-party laboratory analysis (product characterization). QC is a commercially available beverage. The product\u0026rsquo;s primary constituents are the isoflavones genistin and daidzin (and respective metabolites of genistein and daidzein).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eStudy participants were randomized to one of two arms: to receive either Daily QC or placebo. Patients in the intervention arm received Daily QC (QCAN fermented soy) as two 12.5 packets/day approximately or 1 ounce/day between the time of enrollment and RP. Patients in the control arm received daily matched dose placebo. These were taken at time of enrollment to RP (between 4 and 10 weeks prior to surgery). Participants were considered to have completed the study if they had completed all study visits. Study visits included an initial screening and baseline visit, a second visit for assignment of intervention, weekly phone calls thereafter to asses safety and adherence/dosing and a final assessment visit.\u003c/p\u003e \u003cp\u003eTo be eligible for participation, we required that patients had histologically verified PCa at any stage, were \u0026ge;\u0026thinsp;18 years of age and scheduled to be treated by RP within 4 to 10 weeks from screening and enrollment. Patients were excluded if they had previous (within 6 months of enrollment) or concurrent hormonal therapy or chemotherapy; specifically, treatment with 5-alpha reductase inhibitors (finasteride and dutasteride), history of hormone dependent malignancies, concomitant thyroid disease or currently taking thyroid hormone replacement medication, current high-dose soy consumption, micronutrient, or herbal supplements, on soy or vegetarian nutrition, or any other extreme dietary habits, currently taking oral anticoagulants or parenteral injection of low molecular weight heparin (enoxaparin), current or past history of any liver or pancreas disease, history of hypersensitivity to soy-containing products or malabsorption conditions.\u003c/p\u003e \u003cp\u003eThe primary study endpoint was change in serum PSA defined as the difference between baseline PSA value and PSA value at the time of RP. Baseline was defined as the date that an eligible participant enrolled in the trial. The secondary endpoints were changes in other clinical and pathologic endpoints including prognostic Gleason Grade Group, stage, margin status, overall Cancer of the Prostate Risk Assessment (CAPRA) score, lipid levels, testosterone, and health related quality of life (FACT-P score). The target sample size per design was 72.\u003c/p\u003e \u003cp\u003e All patients provided written informed consent prior to administering any study procedures. Interim analysis and monitoring were performed by the principle investigators and presented and reviewed by the independent Data Safety Monitoring Board. This trial was approved by the Yale University institutional review board.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe intent-to-treat (ITT) efficacy analysis of endpoints included data from all randomized study participants. Safety was analyzed using data from all study participants who received at least one dose of QC. The analysis of safety included all events that occurred from the time of the first dose until the participant\u0026rsquo;s final assessment, just prior to RP. Final assessment of primary outcome, PSA as well as change of PSA utilized data from all participants who had end of study information available and complete laboratory analysis. A two-sided Type I error of 0.05 was used as the level of statistical significance.\u003c/p\u003e \u003cp\u003eThe ITT analysis of the primary outcome was conducted using a repeated measures analysis or linear mixed model analysis using the stratification variable of baseline CAPRA risk. A secondary analysis the of primary outcome was performed using a generalized linear model adjusting for baseline PSA value. Continuous secondary outcomes were analyzed using linear mixed models to assess mean changes (pre- to post-surgery). The Gleason score and quality of life (FACT-P), both ordinal variables, were analyzed using a Wilcoxon Signed Rank test. Degree of tumor focality was assessed with the chi-square method.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003ePatients\u003c/h2\u003e\n \u003cp\u003eFrom August 2, 2018 to December 4, 2019, a total of 19 eligible patients were enrolled and randomized; 10 were assigned to the QC group and 9 were assigned to the placebo group. Baseline characteristics and demographics were well balanced between the two groups (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age of patients at time of enrollment in the QC cohort was 60.5 years and 60 years in the placebo cohort. At the time of final analysis, 16 patients were assessed for final measurement of primary outcome. Per CAPRA risk score, 9 (56.2%) patients were considered low and intermediate risk, and 7 (43.8%) were considered high CAPRA risk. Due to low enrollment, and after consultation and recommendation by the DSMB, an interim analysis was conducted after 19 participants had been enrolled, which suggested no statistically significant differences in the primary endpoint. Therefore, the investigators and sponsors elected to terminate the study early.\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline Characteristics of included patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDaily QC (n\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo (n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDifference (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge at Study\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.60 (55.66, 65.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.89 (57.95, 67.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.68 (58.50, 64.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.28 (-8.77, 4.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.60 (6.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e62.89 (6.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.68 (6.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.5 (58.0\u0026ndash;66.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.0 (58.0\u0026ndash;69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e60.0 (58.0\u0026ndash;69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation, number of years\u003c/strong\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.60 (11.42, 13.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.11 (12.76, 15.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.32 (12.44, 14.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.51 (-3.16, 0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.60 (1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.11 (1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.32 (1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.0 (12.0\u0026ndash;14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.0 (12.0\u0026ndash;16.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.0 (12.0\u0026ndash;15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace self-identity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBlack or African American\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (20.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (22.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4 (21.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026minus;\u0026thinsp;2% (-45%, 49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (80.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (77.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (78.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2% (-49%, 45%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHispanic or Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (10.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (00.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (5.26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10% (-39%, 19%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (90.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9 (100.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (94.74%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-10% (-19%, 39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLawrence \u0026amp; Memorial Hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (50.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6 (66.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11 (57.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-16% (-37%, 70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYale University\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (50.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (33.33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (42.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17% (-70%, 37%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarital status\u003c/strong\u003e:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarried or Cohabiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7 (70.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8 (88.89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15 (78.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-19% (-26%, 64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot married/cohabitating\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3 (30.00%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (11.11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2 (10.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19% (-64%, 26%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eChange in serum PSA\u003c/h2\u003e\n \u003cp\u003eThe difference in mean baseline PSA of the QC and Placebo groups was not statistically significant (8.98, 95% CI: 6.07\u0026ndash;11.89 versus 8.66, 95% CI: 6.58\u0026ndash;10.74, respectively). At the end of the study there was no statistically significant difference in PSA in the QC cohort compared to the placebo (8.02, 95% CI: 4.96\u0026ndash;11.09 versus 9.53, 95% CI: 6.73\u0026ndash;12.33) respectively). In terms of the difference between baseline and end of study PSA, there was no statistically significant difference between QC cohort and placebo (0.85, 95% CI: -1.01\u0026ndash;2.71 versus \u0026minus;\u0026thinsp;0.13, 95% CI: -1.46\u0026ndash;1.19 respectively) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea). When stratified by CAPRA risk in the QC cohort compared to placebo, there was no statistically significant difference in baseline PSA, end of study PSA or PSA change from baseline to end of study (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eA. Primary Outcome Bivariate Analysis: PSA, B. Primary Outcome Bivariate Analysis: PSA, Stratified by CAPRA Risk\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eQC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlacebo\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBaseline\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.98 (4.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.66 (2.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.83 (3.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.98 (6.07\u0026ndash;11.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.66 (6.58\u0026ndash;10.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.83 (7.19\u0026ndash;10.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.3 (2.3\u0026ndash;15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.2 (5.1\u0026ndash;12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.7 (2.3\u0026ndash;15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnd of Study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.02 (3.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.53 (3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.68 (3.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.02 (4.96\u0026ndash;11.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.53 (6.73\u0026ndash;12.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.68 (6.78\u0026ndash;10.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.0 (1.7\u0026ndash;15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.8 (4.5\u0026ndash;12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.5 (1.7\u0026ndash;15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Baseline \u0026ndash; End of Study)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16 (3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (2.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.13 (1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85 (-1.01\u0026ndash;2.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.13 (-1.46\u0026ndash;1.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42 (-0.67\u0026ndash;1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6 (-2.8\u0026ndash;5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.1 (-2.5\u0026ndash;2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (-2.8\u0026ndash;5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eB.\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"672\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.38095238095238%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"62.79761904761905%\" colspan=\"3\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.821428571428571%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eQC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eLow Risk\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e6.26 (3.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.08 (2.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.17 (3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e6.26 (2.11 \u0026ndash; 10.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.08 (4.70 \u0026ndash; 11.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.17 (5.00 \u0026ndash; 9.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5.4 (2.3 \u0026ndash; 10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.0 (5.8 \u0026ndash; 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e6.8 (2.3 \u0026ndash; 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnd of Study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e6.50 (3.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.07 (3.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.20 (3.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e6.50 (2.00 \u0026ndash; 11.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.07 (2.82 \u0026ndash; 13.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.20 (4.61 \u0026ndash; 9.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.2 (1.7 \u0026ndash; 10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.7 (4.5 \u0026ndash; 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7.2 (1.7 \u0026ndash; 12.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Baseline \u0026ndash; End of Study)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.24 (1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.27 (1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.02 (1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.24 (-2.35 \u0026ndash; 1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.27 (-1.93 \u0026ndash; 2.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.02 (-1.16 \u0026ndash; 1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.5 (-2.8 \u0026ndash; 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.1 (-1.2 \u0026ndash; 2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.3 (-2.8 \u0026ndash; 2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHigh Risk\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e5 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e11.69 (2.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.40 (2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.67 (2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e11.69 (8.27 \u0026ndash; 15.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.40 (4.78 \u0026ndash; 14.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.67 (8.44 \u0026ndash; 12.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.8 (8.6 \u0026ndash; 15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.5 (5.1 \u0026ndash; 11.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.7 (5.1 \u0026ndash; 15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnd of Study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.92 (4.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e11.49 (1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.59 (3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e9.92 (3.51 \u0026ndash; 16.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e11.49 (8.82 \u0026ndash; 14.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.59 (7.79 \u0026ndash; 13.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e8.3 (7.2 \u0026ndash; 15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.9 (10.8 \u0026ndash; 12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e10.8 (7.2 \u0026ndash; 15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Baseline \u0026ndash; End of Study)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eN (N Missing)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e4 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e2.21 (2.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.67 (1.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.97 (2.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMean (95% CL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e2.21 (-2.10 \u0026ndash; 6.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.67 (-4.61 \u0026ndash; 3.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.97 (-1.45 \u0026ndash; 3.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.340267459138186%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedian (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e2.1 (-0.6 \u0026ndash; 5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e-0.1 (-2.5 \u0026ndash; 0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.950965824665676%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.6 (-2.5 \u0026ndash; 5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.806835066864785%\" valign=\"bottom\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eSecondary Outcomes\u003c/h2\u003e\n \u003cp\u003eThere was no statistically significant difference in Gleason score, clinical stage, surgical margins, percent of biopsy cores involved in cancer, extracapsular extension, lymph node invasion, seminal vesicle invasion or CAPRA score between the QC and placebo groups. In addition, there were no statistically significant differences between the QC arm and placebo arm in end-of-study or change in lipids, free and total testosterone (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cp\u003eIn the evaluation of quality-of-life measures, there was no significant difference in change of FACT-P score from baseline to end of study between the QC arm and the placebo arm (diff\u0026thinsp;=\u0026thinsp;9.38, 95% CI: -1.22\u0026ndash;19.98, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Furthermore, there was no significant difference in change of physical well-being, social well-being, emotional well-being, functional well-being, or PWB, SWB, EWB, FWB or Prostate cancer subscale, sub scores.\u003c/p\u003e\n \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\n \u003ch2\u003eSafety\u003c/h2\u003e\n \u003cp\u003eA total of 4 adverse events in 3 patients in the QC arm and 1 adverse event in the placebo arm were reported in the study (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). There was one serious adverse event (SAE) in the QC group requiring hospitalization: a participant presented with an enlarging aortic aneurysm and pneumonia during the trial period, but the SAE was deemed unrelated to QC administration. There were no serious adverse events that resulted in trial discontinuation in either cohort. There were no deaths during the trial period.\u003c/p\u003e\n \u003cp\u003eTable 3: Adverse Events\u0026nbsp;\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"728\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEvent name\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eQC\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(n events, n patients)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlacebo \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cem\u003e(n events, n patients)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003cem\u003e(n events, n patients)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(0, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003eAortic Aneurysm and Pneumonia\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(0, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003eNausea / Dizzyness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(0, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003eAtrial Fibrillation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(1, 1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e(2, 2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eNumber of unique participants \u0026nbsp;with AE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(4, 3)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(1, 1)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e(5, 4)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.762688614540465%\" valign=\"top\"\u003e\n \u003cp\u003eAE led to study discontinuation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.713305898491083%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.262002743484224%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eKey: * denotes SAE\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe performed a double blind, randomized, clinical trial to evaluate the effect of a soy product, QC, on PSA in patients with PCa prior to RP. We found no statistically significant difference in PSA changes in patients treated with QC compared to Placebo. We also found no difference in surgical specimens (including Gleason score, surgical margins, clinical stage, extracapsular extension, lymph node or semivesical invasion) or laboratory parameters (free, total and bioavailable testosterone, amylase, CRP, C-reactive protein, HDL, LDL, Lipase, ESR, TSH, triglycerides) in patients treated with QC. Furthermore, we found no changes in quality of life for patients treated with QC compared to placebo. There were no serious adverse events directly attributed to QC during the trial period. To our knowledge, this is the first randomized control trial to evaluate a fermented soy product\u0026rsquo;s effect on PSA and surgical parameters in patients with PCa undergoing RP. Even though the study was terminated prematurely due to inability to recruit, and thus did not achieve the design power, contributes to a growing body of literature aimed toward evaluating low-toxicity interventions in the tertiary prevention of morbidity and mortality in patients with PCa.\u003c/p\u003e \u003cp\u003eSoy isoflavones have been previously investigated for their relationship with PCa. In terms of risk of PCa, a systematic review and metanalysis summarized the results of 30 studies investigating soy product intake and PCa risk. The metanalysis found a significant association of soy intake with reduced risk of PCa (Total soy food (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), genistein (p\u0026thinsp;=\u0026thinsp;0.008), daidzein (p\u0026thinsp;=\u0026thinsp;0.018), and unfermented soy food (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001))(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In patients with PCa, a recent systematic review assessed the role of genistein in PCa parameters, where the effect of genistein supplementation was investigated in two studies(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Lazarevic et al. investigated the effect of 30 mg of genistein daily for three to six weeks prior to RP compared to placebo in a randomized phase 2 clinical trial of 54 men with localized PCa. Compared to placebo, patients treated with genistein had statistically insignificant change in PSA (p\u0026thinsp;=\u0026thinsp;0.051), however they had a significant difference in cellular response (p\u0026thinsp;=\u0026thinsp;0.033), and cell proliferation (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) However, this trial was evaluated and was found to have a high or unclear risk of bias on 4 out of 7 criteria but low risk of bias for sequence generation and blinding as well as selective outcome reporting. In contrast, in a relatively low risk of bias trial, randomization of 60 mg of genistein daily versus placebo for 12 weeks in men enrolled in watchful waiting, yielded no impact on mean change in PSA(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Similar to the findings of our clinical trial on fermented soy, Hamilton-Reeves et al. performed a double-blind, randomized, placebo-controlled trial to examine the effects of soy isoflavone capsules in patients with localized PCa for 6 weeks prior to RP. There was no statistically significant difference in change in PSA, testosterone, estrogen, or total cholesterol(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Q-CAN has been shown to reduces viability and increase apoptosis of cancer cells in a fermentation, concentration and time dependent manner. This suggests that fermentation of soy results in the production of metabolites that can reduce cancer cell viability, and induce cellular apoptosis(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Interestingly it was shown that these actions occurred independent of genistein content.\u003c/p\u003e \u003cp\u003eAn important distinction of our study from the current available literature on PCa and soy, is that our trial investigated the fermented soy product QC specifically in a randomized control setting. Strengths of our study include the strict inclusion criteria and its randomized prospective nature. Additionally, unlike prior trials on soy and PCa, our study captured PSA results, laboratory values, surgical parameters, and quality of life measures.\u003c/p\u003e \u003cp\u003eThere are several important limitations to note. Most significantly, this trial included a small sample size due to early terminiation and failed to achieve the protocol determined sample size. Therefore, adequate statistical power was not reached to assess the prespecified study endpoints. As additional considerations we did not account for longer-term outcomes or data regarding continued patient exposure to QC post-treatment. Additionally, PSA is a surrogate measure which may not adequately represent cancer risk or response and may fail to identify a variety of antitumor effects. In addition, the length of the exposure was relatively short (a minimum of 2 weeks), which may also be inadequate to lead to measurable differences in clinical parameters. To account for these limitations, further trials should be cognizant of potential sample size limitations, considerations of exposure length, and should incorporate a wider range of clinical and biological endpoints.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eA short exposure to a fermented soy beverage among patients with localized prostate cancer was not associated with changes in PSA levels or other prostate cancer characteristics, including grade and stage or serum testosterone. As a consequence of early termination, study power, per design, was not achieved.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eData that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e All methods were carried out in accordance with relevant guidelines and regulations. All patients provided written informed consent prior to administering any study procedures. Interim analysis and monitoring were performed by the principle investigators and presented and reviewed by the independent Data Safety Monitoring Board. This trial was approved by the Yale University institutional review board, Protocol Number: 2000020868\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e BESO Biologic Research, Inc.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Trial Design: MSL, AA, Secured Funding: MSL, AA, Statistics: SDL, TF, TW, JR, WZM, TCK, MSL, Patient recruitment: BMS, JB, JR, MSL\u003c/p\u003e\n\u003cp\u003eWrote Manuscript: SDL, MSL, Manuscript Review: all authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e NA\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s information:\u0026nbsp;\u003c/strong\u003eDr. Michael Leapman\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Email: [email protected]\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 203-785-2140\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 800 Howard Ave Fl 3, New Haven, CT 06519\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Department of Urology, Yale School of Medicine, New Haven CT\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: a cancer journal for clinicians. 2022;72(1):7-33. Epub 20220112. doi: 10.3322/caac.21708. PubMed PMID: 35020204.\u003c/li\u003e\n\u003cli\u003eGupta N, Patel HD, Taylor J, Borin JF, Jacobsohn K, Kenfield SA, et al. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. Prostate Cancer Prostatic Dis. 2022;25(3):444-52. Epub 20220705. doi: 10.1038/s41391-022-00553-2. PubMed PMID: 35790788.\u003c/li\u003e\n\u003cli\u003eLoeb S, Fu BC, Bauer SR, Pernar CH, Chan JM, Van Blarigan EL, et al. Association of plant-based diet index with prostate cancer risk. Am J Clin Nutr. 2022;115(3):662-70. doi: 10.1093/ajcn/nqab365. PubMed PMID: 34791008; PubMed Central PMCID: PMC8895206.\u003c/li\u003e\n\u003cli\u003eFraser GE, Jaceldo-Siegl K, Orlich M, Mashchak A, Sirirat R, Knutsen S. Dairy, soy, and risk of breast cancer: those confounded milks. Int J Epidemiol. 2020. Epub 2020/02/26. doi: 10.1093/ije/dyaa007. PubMed PMID: 32095830.\u003c/li\u003e\n\u003cli\u003eKucuk O. Soy foods, isoflavones, and breast cancer. Cancer. 2017;123(11):1901-3. Epub 2017/03/07. doi: 10.1002/cncr.30614. PubMed PMID: 28263364.\u003c/li\u003e\n\u003cli\u003eWu YC, Zheng D, Sun JJ, Zou ZK, Ma ZL. Meta-analysis of studies on breast cancer risk and diet in Chinese women. Int J Clin Exp Med. 2015;8(1):73-85. Epub 2015/03/19. PubMed PMID: 25784976; PubMed Central PMCID: PMC4358431.\u003c/li\u003e\n\u003cli\u003eZhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, et al. Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry. Cancer. 2017;123(11):2070-9. Epub 2017/03/07. doi: 10.1002/cncr.30615. PubMed PMID: 28263368; PubMed Central PMCID: PMC5444962.\u003c/li\u003e\n\u003cli\u003eOuyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, et al. Fermented Soy Drink (Q-CAN\u0026reg; PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutr Cancer. 2022:1-10. Epub 20220523. doi: 10.1080/01635581.2022.2077385. PubMed PMID: 35603899.\u003c/li\u003e\n\u003cli\u003eSu SJ, Yeh TM, Chuang WJ, Ho CL, Chang KL, Cheng HL, et al. The novel targets for anti-angiogenesis of genistein on human cancer cells. Biochem Pharmacol. 2005;69(2):307-18. Epub 20041119. doi: 10.1016/j.bcp.2004.09.025. PubMed PMID: 15627483.\u003c/li\u003e\n\u003cli\u003eBattaglia A, Devos G, Boeckx G, Goeman L, Tosco L, de Meerleer G, et al. Prostate-Specific Antigen Modulatory Effect of a Fermented Soy Supplement for Patients with an Elevated Risk of Prostate Cancer: a Non-Randomized, Retrospective Observational Registration. Curr Urol. 2020;14(3):142-9. Epub 20201013. doi: 10.1159/000499246. PubMed PMID: 33224007; PubMed Central PMCID: PMC7659407.\u003c/li\u003e\n\u003cli\u003eMehal W, Secor E, Weiss T, Fields M, Leapman M, Ali A. Isoflavone Stability Quality Control Assessment of Q-CAN\u0026reg; Plus, a Novel Fermented Soy Beverage (P12-034-19). Current Developments in Nutrition. 2019;3(Supplement_1):nzz035. P12-4-19.\u003c/li\u003e\n\u003cli\u003eApplegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. Nutrients. 2018;10(1). Epub 20180104. doi: 10.3390/nu10010040. PubMed PMID: 29300347; PubMed Central PMCID: PMC5793268.\u003c/li\u003e\n\u003cli\u003eHackshaw-McGeagh LE, Perry RE, Leach VA, Qandil S, Jeffreys M, Martin RM, et al. A systematic review of dietary, nutritional, and physical activity interventions for the prevention of prostate cancer progression and mortality. Cancer Causes Control. 2015;26(11):1521-50. Epub 20150909. doi: 10.1007/s10552-015-0659-4. PubMed PMID: 26354897; PubMed Central PMCID: PMC4596907.\u003c/li\u003e\n\u003cli\u003eLazarevic B, Boezelijn G, Diep LM, Kvernrod K, Ogren O, Ramberg H, et al. Efficacy and safety of short-term genistein intervention in patients with localized prostate cancer prior to radical prostatectomy: a randomized, placebo-controlled, double-blind Phase 2 clinical trial. Nutr Cancer. 2011;63(6):889-98. Epub 20110629. doi: 10.1080/01635581.2011.582221. PubMed PMID: 21714686.\u003c/li\u003e\n\u003cli\u003eKumar NB, Cantor A, Allen K, Riccardi D, Besterman-Dahan K, Seigne J, et al. The specific role of isoflavones in reducing prostate cancer risk. The Prostate. 2004;59(2):141-7. doi: 10.1002/pros.10362. PubMed PMID: 15042614.\u003c/li\u003e\n\u003cli\u003eHamilton-Reeves JM, Banerjee S, Banerjee SK, Holzbeierlein JM, Thrasher JB, Kambhampati S, et al. Short-term soy isoflavone intervention in patients with localized prostate cancer: a randomized, double-blind, placebo-controlled trial. PLoS One. 2013;8(7):e68331. Epub 20130712. doi: 10.1371/journal.pone.0068331. PubMed PMID: 23874588; PubMed Central PMCID: PMC3710024.\u003c/li\u003e\n\u003cli\u003eOuyang X, Chen Y, Tejaswi BS, Arumugam S, Secor E, Weiss TR, et al. Fermented Soy Drink (Q-CAN(R) PLUS) Induces Apoptosis and Reduces Viability of Cancer Cells. Nutr Cancer. 2022;74(10):3670-8. Epub 2022/05/24. doi: 10.1080/01635581.2022.2077385. PubMed PMID: 35603899.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"prostate cancer, PSA, fermented soy, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-3240223/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3240223/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2–5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline – end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p \u0026gt; 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p \u0026gt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShort exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinicalTrials.gov Identifier: NCT03532308, May 9, 2018\u003c/p\u003e","manuscriptTitle":"A Randomized Controlled Trial of a Fermented Soy Beverage Among Patients with Localized Prostate Cancer Prior to Radical Prostatectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-17 02:32:33","doi":"10.21203/rs.3.rs-3240223/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2023-08-21T13:38:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-21T13:03:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-08-10T05:35:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Urology","date":"2023-08-07T00:51:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f063259-05a8-4ffd-bdd8-a9e98f3d12fe","owner":[],"postedDate":"August 17th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-07T19:59:33+00:00","versionOfRecord":{"articleIdentity":"rs-3240223","link":"https://doi.org/10.1186/s12894-024-01483-y","journal":{"identity":"bmc-urology","isVorOnly":false,"title":"BMC Urology"},"publishedOn":"2024-05-03 19:57:26","publishedOnDateReadable":"May 3rd, 2024"},"versionCreatedAt":"2023-08-17 02:32:33","video":"","vorDoi":"10.1186/s12894-024-01483-y","vorDoiUrl":"https://doi.org/10.1186/s12894-024-01483-y","workflowStages":[]},"version":"v1","identity":"rs-3240223","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3240223","identity":"rs-3240223","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}