D-Cycloserine for Treatment of Chronic Low Back Pain: Results from a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

D-Cycloserine for Treatment of Chronic Low Back Pain: Results from a Randomized, Double-Blind, Placebo-Controlled Clinical Trial | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search D-Cycloserine for Treatment of Chronic Low Back Pain: Results from a Randomized, Double-Blind, Placebo-Controlled Clinical Trial View ORCID Profile Joana Barroso , View ORCID Profile Andrew D. Vigotsky , View ORCID Profile Santiago Espinosa Salas , View ORCID Profile Olivia Cong , View ORCID Profile Narina Simonan , View ORCID Profile A. Vania Apkarian , View ORCID Profile Thomas Schnitzer doi: https://doi.org/10.1101/2025.09.14.25335705 Joana Barroso 1 Department of Anesthesiology; Center for Translational Pain Research, Feinberg School of Medicine, Northwestern University , Chicago, IL 2 Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL 5 Department of Clinical Neurosciences and Mental Health, University of Porto MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Joana Barroso For correspondence: joana.barroso.monteiro{at}northwestern.edu Andrew D. Vigotsky 3 Department of Neuroscience, Feinberg School of Medicine, Northwestern University , Chicago, IL 6 Neuroscience Center, Department of Cell Biology & Physiology, and Department of Pharmacology, University of North Carolina at Chapel Hill , Chapel Hill, NC PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Andrew D. Vigotsky Santiago Espinosa Salas 2 Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Santiago Espinosa Salas Olivia Cong 3 Department of Neuroscience, Feinberg School of Medicine, Northwestern University , Chicago, IL Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Olivia Cong Narina Simonan 2 Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Narina Simonan A. Vania Apkarian 1 Department of Anesthesiology; Center for Translational Pain Research, Feinberg School of Medicine, Northwestern University , Chicago, IL 2 Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL 3 Department of Neuroscience, Feinberg School of Medicine, Northwestern University , Chicago, IL PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for A. Vania Apkarian Thomas Schnitzer 1 Department of Anesthesiology; Center for Translational Pain Research, Feinberg School of Medicine, Northwestern University , Chicago, IL 2 Department of Physical Medicine and Rehabilitation, Feinberg School of Medicine, Northwestern University , Chicago, IL 4 Department of Rheumatology, Feinberg School of Medicine, Northwestern University , Chicago, IL MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thomas Schnitzer Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Objective Chronic low back pain (cLBP) is a leading cause of global disability, with current treatments offering limited and inconsistent relief. D-cycloserine (DCS), a partial NMDA receptor agonist and FDA-approved antimicrobial, has shown promise in preclinical models for reducing neuropathic pain and its negative emotional impact. Building on these findings and a positive pilot study, we conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of DCS in adults with cLBP. Methods Participants with cLBP (n=203) were randomized to receive 200 mg DCS or placebo twice daily for 12 weeks, followed by a 12-week placebo phase. The primary outcome was pain intensity (numeric rating scale, NRS) at 12 weeks; secondary outcomes included pain intensity at 24 weeks, safety, and patient-reported psychological measures. Results DCS had negligible effects on pain compared to placebo at both 12 weeks (adjusted effect: −0.07/10 NRS units, 95% CI: (−0.67, 0.53), p = 0.78) and at 24 weeks (adjusted effect: −0.22/10 NRS units, 95% CI: (−0.84, 0.40), p = 0.39). Adverse events were similar between groups. Exploratory outcomes also showed no significant effects. Conclusion Our results indicate that 12 weeks of DCS 400 mg/day does not provide clinically meaningful analgesia in cLBP, though it is well tolerated. These findings highlight the challenges of translating preclinical neuropathic pain results to heterogeneous clinical pain populations. 1. Introduction Low back pain (LBP) represents a significant global health challenge, affecting over 619 million individuals worldwide in 2020, with projections indicating this number will surge to 843 million by 2050 1 . As a leading cause of global disability, LBP profoundly impacts individual well-being, physical function, and quality of life 2 - 4 . It also has a substantial impact on healthcare expenditure, and in the US alone, reached approximately $134.5 billion in 2016 (for low back and neck pain), surpassing spending on other major conditions 5 . Current treatments for chronic low back pain (cLBP) generally provide only small to moderate benefits 6 . Many cLBP patients receive multiple treatments with limited success, and many continue to experience pain or disability after completing or terminating medical treatments 7 . Moreover, although opioid analgesics are no more effective than non-opioid treatments for cLBP 8 , 9 , opioid prescriptions remain common 10 , fueling the ongoing opioid crisis and emphasizing the urgent need for more effective, non-addictive therapies. D-cycloserine (DCS), an FDA-approved antimicrobial agent used as a second-line treatment for tuberculosis, has shown potential in treating chronic pain 11 , 12 . DCS is a partial agonist at the glycine site of the NMDA (N-methyl-D-aspartate) receptor. Consequently, at lower doses, it enhances NMDA receptor function, whereas at higher doses, it may act as a functional NMDA receptor antagonist 13 . Preclinical and clinical studies have demonstrated that DCS facilitates fear extinction and cognitive flexibility by potentiating NMDA receptor signaling during extinction training, thereby promoting adaptive synaptic plasticity 14 , 15 . These effects appear to be mediated via corticolimbic circuits, including the medial prefrontal cortex (mPFC) and amygdala, which are critical for emotional regulation and aversive learning 16 , 17 . Given that chronic pain is posited to be a disorder of maladaptive learning and affective dysregulation, targeting these circuits with DCS offers a novel therapeutic strategy 12 , 18 . Consistent with this rationale, preclinical studies from our group have shown that DCS reduces pain-like behaviors in rodent models of chronic pain, including spared nerve injury and chemotherapy-induced neuropathy 12 . The effects were dose-dependent and increased with prolonged use and associated with persistent analgesia for over a month after discontinuation 12 . The analgesic effects of DCS appeared to be specific to the injured areas, without affecting normal pain sensitivity elsewhere. Importantly, these analgesic effects required chronic dosing, suggesting the effect of DCS relies on long-term adaptation rather than immediate analgesia. Following these experimental results, our group conducted a small proof-of-concept pilot study of DCS in individuals with cLBP. In this randomized, parallel-group design with a placebo control, the DCS group showed a greater reduction in pain than the placebo group after 6 weeks of treatment 19 . Secondary analyses exploring psychological dimensions of pain revealed that DCS may positively influence emotional well-being 19 . Building on compelling preclinical evidence and encouraging results from our initial human pilot study, we conducted a larger phase 2 study of DCS in patients with cLBP to investigate the efficacy and safety of DCS. The primary outcome measure of this study was the efficacy of pain reduction relative to placebo, assessed using the Numeric Rating Scale (NRS) pain ratings at the 12-week endpoint. Secondary outcomes included safety evaluation, longer-term pain relief (24 weeks), and a comprehensive set of patient-reported outcomes and psychological assessments, providing an evaluation of DCS’s impact on both pain intensity and associated psychological factors in cLBP management. 2. Methods 2.1 Study Design and Oversight This parallel group, placebo-controlled, randomized controlled trial (RCT) was conducted at Northwestern University in Chicago, IL. The study protocol was approved by the Northwestern Institutional Review Board (STU00205398) and the study was registered on ClinicalTrials.gov (identifier: NCT03535688 ). The full trial protocol and statistical analysis plan are publicly accessible on the registry website. Deidentified individual participant data and supporting documents will be made available upon request to the corresponding author, contingent on a data use agreement. All participants provided written informed consent before an initial screening to determine eligibility and interest. Participants recorded their pain levels twice daily using an electronic diary (eDiary) accessible via smartphone or computer. During the screening period, they discontinued medications used for cLBP and were provided acetaminophen (maximum dose 3000 mg/day) for pain relief. A baseline visit was scheduled after 10–14 days. To qualify for randomization, participants needed a mean pain level of ≥4 and ≤9 over 5– 7 days prior to the baseline visit (with at least five eDiary entries during this period) and a pain level of ≥4 at baseline. At the baseline visit, participants completed questionnaires assessing pain, function, psychological factors, and quality of life, followed by a brain MRI (not reported in this paper). Eligible participants were then randomized to receive either 200 mg of DCS or a placebo, taken twice daily in identical capsules to ensure blinding. Follow-up visits were conducted at 2, 6, 12, and 24 weeks after randomization. At each visit, participants completed questionnaires evaluating pain intensity and characteristics, and safety data were collected. Study medication was dispensed at the 2-week and 6-week visits. At the 12-week visit, participants underwent a second brain MRI along with regular assessments. Subsequently, all participants received placebo to evaluate the persistence of treatment effects over the next 12 weeks. Throughout the study, participants continued to record pain levels via the eDiary and were provided with rescue acetaminophen to take as needed. 2.2 Participants Participants were recruited from two primary sources: Northwestern Medicine (NM) and the Shirley Ryan AbilityLab (SRALab) healthcare system, as well as the broader Chicago community. Recruitment from the Chicago community was supported through social media platforms like Facebook and third-party vendors such as ClinicalConnection . These combined approaches successfully facilitated participant enrollment for the trial. Eligible participants for this study were adults aged 18 years or older with a history of low back pain lasting at least six months. Participants were required to be in generally stable health, willing to discontinue all other pain medications for chronic back pain, and abstain from alcohol during the study. Women of childbearing potential had to use effective contraception or be postmenopausal for at least one year. All participants were required to provide informed consent, agree to record their pain levels and treatment adherence via an eDiary, and comply with the study protocols. Exclusion criteria included systemic symptoms such as fever, evidence of rheumatoid arthritis or other specific spinal conditions, recent back surgery, epidural steroid injections within the last three months, or litigation or disability claims related to back pain. Individuals with a history of seizures, significant psychiatric disorders, substance abuse, abnormal lab results, or medical conditions such as severe renal or cardiac disease were excluded. Participants using the following medications: ethionamide, dilantin, isoniazid medications, recreational drugs, or medical marijuana, or those with intra-axial implants, were not eligible. Pregnancy, breastfeeding, or inability to use effective contraception also disqualified participants. Additionally, any recent changes in medication or physical therapy regimens for back pain, as well as participation in other clinical trials within the last 90 days, were exclusionary. 2.3 Randomization Participants were randomized in a 1:1 ratio to receive either DCS or placebo using a computer-generated permuted block randomization scheme with varying block sizes (2 and 4); randomization was performed on April 4, 2018, by an independent investigator not involved in other aspects of the study. Treatment allocation was concealed using sequentially numbered containers. Study medications were provided in identical opaque capsules to maintain double blinding. A designated unblinded staff member, who had no involvement in clinical assessments, was responsible for medication assignment and maintained the randomization code. This code was only accessible for documented emergencies requiring treatment unblinding after consultation with the site and principal investigator. The randomization codes were made available to study statisticians after the database lock at study conclusion. 2.4 Outcomes and Assessments The primary outcome measure of this study was the efficacy of pain reduction, assessed using the numeric rating scale (NRS). Specifically, the mean NRS scores for the 7 days preceding the 12-week endpoint in the DCS group were compared to those in the placebo group, adjusted for baseline pain (mean NRS score from the 7 days preceding randomization). Pain was measured using an 11-point NRS scale. Secondary outcome measures included pain at 24 week, evaluated between weeks 12 and 24 after the discontinuation of DCS therapy. Exploratory outcomes including a variety of patient-reported outcomes and psychological assessments were collected at various time points to provide a comprehensive understanding of the treatment’s impact. These assessments included the Patient Global Assessment (PGA), the Patient Global Impression of Change (PGIC), and the McGill Pain Questionnaire (MPQ), which were administered at screening, Week 12, and Week 24. Similarly, the painDETECT instrument, Beck Depression Inventory (BDI) – Second Version, Positive and Negative Affect Schedule (PANAS), Pain Catastrophizing Scale (PCS), and other functional and psychological measures, including the Oswestry Disability Index (ODI) and SF-12 Health Survey, were collected at screening, Week 12, and Week 24. (add refs) 2.5 Protocol Deviation in Treatment Assignment Study treatment allocation was in a 1:1 ratio of DCS to placebo in permuted blocks of 2 and 4. After the first 170 participants were entered into the study, errors in study drug allocation occurred such that many participants did not receive their appropriately allocated treatment. Therefore, all efficacy analyses were conducted using only the first 170 participants who received drug based on the correct allocation assignment. The safety analyses included all participants, with participants being assigned to the treatment that they actually received. 2.6 Statistical Analysis The sample size for this study was determined using data from a prior pilot trial 19 ; based on this data, our expected effect size was estimated at Cohen’s d = 0.4 between the treatment and placebo groups. To achieve 80% statistical power at a significance level of α = 0.05, it was calculated that 98 participants per group would be required. To account for an anticipated dropout rate of 20% at the primary endpoint of Week 12, the adjusted sample size increased to 122 participants per group, resulting in a total of 244 participants for the study. No interim analyses were planned or performed. Baseline pain was calculated as the mean of all NRS ratings during the week preceding randomization, with no missing data due to mandatory compliance (≥ 5 ratings). Week 12 pain was defined as the mean of all ratings during that week. Missing data were categorized into six mechanisms based on participants’ self-report: withdrawal of consent, lack of efficacy, loss to follow-up, adverse events, noncompliance, or early study termination. Multivariate imputation by chained equations (MICE) was employed, incorporating baseline pain, age, sex, and prior pain ratings. Participants in withdrawal, loss to follow-up, noncompliance, or early termination groups were imputed under missing-at-random assumptions using randomized group models. Those discontinuing due to lack of efficacy or adverse events were imputed under a “jump-to-reference” assumption using placebo group models. Imputation was performed separately for each treatment arm to account for potential interaction effects. The primary analysis assessed the effect of DCS on Week 12 pain relative to placebo, adjusted for baseline pain, using an analysis of covariance (ANCOVA) estimated with ordinary least squares: where y i is Week 12 pain, group i indicates treatment assignment (DCS=1, placebo=0), and pre i is the baseline pain for subject i . Model fits were assessed by examining residual behavior. Effect estimates were reported with 95% confidence intervals (CI), and p -values for the primary outcomes were derived from a randomization test, in which randomizations were performed within each randomization block. As a secondary outcome, we examined the effect of DCS on pain ratings at Week 24 using the same model, 12 weeks after DCS participants transitioned to placebo. Finally, we estimated and contrasted the above treatment effects between males and females by including sex and group-by-sex terms in the model. As a sensitivity analysis, we performed an as-treated analysis, in which all participants— including those who were misrandomized—were analyzed based on the treatment they received. Notably, this analysis is inconsistent with the randomization structure and ITT principles. Secondary analyses were conducted for the remaining outcomes, which were modeled using ANCOVAs (with baseline as a covariate) or ordinal regression. When model assumptions were clearly violated, heteroskedasticity was modeled using the HC3 sandwich estimator and departures from normality were addressed using permutations and the bias-corrected and accelerated bootstrapped CIs. Analyses were conducted using R (version 4.0.0), with MICE (version 3.16.0) for imputation and concurve for consonance functions. All modifications and assumptions were transparently reported. 3. Results 3.1 Trial population and baseline characteristics A total of 436 participants were screened, with 233 excluded, primarily for not meeting inclusion criteria (n=136). Of the 203 randomized participants, 102 were allocated to the DCS group and 101 to placebo. The efficacy population included 86 DCS and 84 placebo participants who received at least one dose of the intervention, while all 203 randomized participants were included in the safety analysis. By Week 12, 73 DCS and 76 placebo participants completed the primary endpoint assessment, decreasing to 57 and 62, respectively, by Week 24. Discontinuations were due to loss to follow-up, noncompliance, adverse events, or lack of efficacy. Notably, protocol deviations led to the exclusion of 27 DCS and 6 placebo participants from efficacy analyses but not safety analyses. Figure 1 shows participant flow details. Download figure Open in new tab Figure 1. CONSORT flow diagram of participant enrollment, allocation, follow-up, and analysis. A total of 436 participants were screened for eligibility, of which 233 were excluded, primarily for not meeting inclusion criteria (n=136), followed by pain scores/demographics (n=48), laboratory assessments (n=37), non-compliance with study (n=25), medical history (n=19), unwillingness to discontinue other pain medication (n=5), and unwillingness to abstain from alcohol (n=2). A total of 203 participants were randomized, with 102 allocated to the D-cycloserine (DCS) group and 101 to the placebo group. Among all randomized, 86 participants in the DCS group and 84 in the placebo group received at least one dose of the assigned intervention and were included in the efficacy population (primary sample). All 203 randomized participants were included in the safety population. 73 participants in the DCS group and 76 in the placebo group completed the primary endpoint assessment at Week 12. By Week 24, completion rates decreased to 57 participants in the DCS group and 62 in the placebo group. Discontinuation reasons included loss to follow-up, loss of interest in participation, noncompliance, adverse events, and lack of efficacy. The primary efficacy analysis at Week 12 included 86 participants in the DCS group and 84 in the placebo group, while efficacy analyses at Week 24 included 57 participants in the DCS group and 62 in the placebo group. The final analysis included 86 DCS and 84 placebo participants for primary efficacy analysis from baseline to Week 12. The safety analysis encompassed 113 DCS and 90 placebo participants. Week 24 efficacy analysis included 57 DCS and 62 placebo participants. Notably, 27 participants in the DCS group and 6 in the placebo group were incorrectly allocated (protocol deviation identified during quality control procedures) and excluded from efficacy analysis while remaining in the safety analysis in order to maintain the integrity of the study results. Measured baseline demographics and clinical characteristics were similar between the DCS (n=86) and placebo (n=84) groups ( Table 1 ). View this table: View inline View popup Download powerpoint Table 1. Demographic characteristics of study participants by treatment group. Values are presented as mean ± SD for numerical variables and number (percentage) for categorical variables. BDI-II = Beck Depression Inventory – Second Version; MPQ = McGill Pain Questionnaire; ODI = Oswestry Disability Index; PANAS = Positive and Negative Affect Schedule; PCS = Pain Catastrophizing Scale; PGA = Patient Global Assessment; PGIC = Patient Global Impression of Change; SD = Standard deviation; SF-12 = 12-Item Short Form Health Survey; painDETECT = Neuropathic pain screening questionnaire. 3.2 Primary Outcome The ITT analysis revealed negligible differences in pain between the DCS and placebo groups at Week 12. The adjusted treatment effect was −0.07 NRS units; the data were compatible (95% CI) with effects ranging from −0.67 to 0.53 NRS units, where negative values indicate lower pain in the DCS group. The 12-week treatment effects within each sex and the differences between the treatment effects across sexes were also highly compatible with the null hypotheses of no effect of DCS and no differences in the DCS effect between sexes ( Table 2 ). View this table: View inline View popup Download powerpoint Table 2. Main outcome, secondary and exploratory outcomes at 12 weeks. Analyses for primary and secondary outcomes were conducted using ANCOVA adjusted for baseline pain scores. For the primary outcome (ITT pain at Week 12), blocked permutation testing was employed to maintain randomization integrity, and missing data were imputed using multivariate imputation by chained equations (MICE). Exploratory continuous outcomes (e.g., MPQ, PANAS, PDQ) were analyzed using ANCOVA, with HC3 sandwich estimators applied where appropriate to address heteroskedasticity and permutations applied when substantial departures from residual normality were present. PGA and PGIC were assessed using ordinal regression. BDI-II = Beck Depression Inventory – Second Version; MPQ = McGill Pain Questionnaire; ODI = Oswestry Disability Index; PANAS = Positive and Negative Affect Schedule; PCS = Pain Catastrophizing Scale; PGA = Patient Global Assessment; PGIC = Patient Global Impression of Change; SD = Standard deviation; SF-12 = 12-Item Short Form Health Survey; painDETECT = Neuropathic pain screening questionnaire. 3.3 Secondary outcomes 3.3.1 24-week analysis The ITT analysis revealed no significant differences in pain between the DCS and placebo groups at Week 24. The adjusted treatment effect was −0.22 NRS units; the data were compatible with effects ranging from −0.85 to 0.40 NRS units. The 24-week treatment effects within each sex and the differences between the treatment effects across sexes were also highly compatible with the null hypotheses of no effect of DCS and no differences in the DCS effect between sexes ( Table 3 ). These results align with the primary Week 12 findings, indicating that the effect of daily 400 mg of DCS relative to placebo on pain ratings at 24 weeks is precisely estimated around 0. View this table: View inline View popup Download powerpoint Table 3. Secondary and exploratory outcomes at Week 24. Analyses for primary and secondary outcomes were conducted using ANCOVA adjusted for baseline pain scores. For the primary outcome (ITT pain at Week 24), blocked permutation testing was employed to maintain randomization integrity, and missing data were imputed using multivariate imputation by chained equations (MICE). Exploratory continuous outcomes (e.g., MPQ, PANAS, PDQ) were analyzed using ANCOVA, with HC3 sandwich estimators applied where appropriate to address heteroskedasticity and permutations applied when substantial departures from residual normality were present. PGA and PGIC were assessed using ordinal regression. BDI-II = Beck Depression Inventory – Second Version; MPQ = McGill Pain Questionnaire; ODI = Oswestry Disability Index; PANAS = Positive and Negative Affect Schedule; PCS = Pain Catastrophizing Scale; PGA = Patient Global Assessment; PGIC = Patient Global Impression of Change; SD = Standard deviation; SF-12 = 12-Item Short Form Health Survey; painDETECT = Neuropathic pain screening questionnaire. 3.3.2 Safety analysis A total of 193 adverse events (AEs) were reported among 98 unique participants during the study, with 111 events occurring in the placebo group and 82 in the DCS group. Most events were mild in severity (n = 115, 60.2%), followed by moderate (n = 73, 37.8%), and severe (n = 5, 2.6%). Only four events (2.1%) were considered serious. Most adverse events (n = 149) were judged unrelated to the investigational product, with smaller numbers considered unlikely related (n = 23) or possibly related (n = 21). All serious adverse events were deemed unrelated to the study drug. A detailed breakdown of AEs by organ system and severity is provided in Supplementary Table 1. No unexpected safety signals or concerning patterns were identified. Overall, the treatment was well tolerated. 3.4 Exploratory outcomes The as-treated analysis with imputation at Week 12 showed a nonsignificant treatment effect for DCS, with an estimated adjusted pain reduction of −0.1; the data were compatible with effects ranging from −0.7 to 0.4, excluding clinically meaningful effects in the broader (misallocated) sample. By Week 24, the adjusted effect was still modest ( Table 2 ). These exploratory findings align with the primary intention-to-treat (ITT) results, reinforcing the conclusion that DCS did not demonstrate, nor were they compatible with, clinically significant analgesic efficacy compared to placebo at either timepoint. At both Weeks 12 and 24, participants receiving active treatment reported worse on average perceived improvement compared to placebo (OR = 0.3, Table 2 ; OR = 0.4, Table 3 ); however, these estimates were imprecise. Similarly, at Week 24, PGA was lower on average in the DCS group compared to the placebo group (OR = 0.4, Table 3 ), but this difference was not precisely estimated. All other outcomes tended to have negligible effects, estimated to be close to zero. Discussion In this randomized, placebo-controlled trial, we evaluated the analgesic efficacy and safety of 400 mg daily DCS for the treatment of chronic low back pain over a 24-week period. At the provided dose and duration, DCS did not demonstrate a clinically significant reduction in pain intensity compared to placebo at either the Week 12 primary endpoint or the Week 24 follow-up. These findings were consistent across both ITT and as-treated analyses. Moreover, exploratory analyses were consistent with these results. Importantly, DCS was well tolerated, with a comparable adverse event profile to that of the placebo and no unexpected safety concerns. Taken together, our results do not support the efficacy of DCS as an analgesic intervention in this population. D-cycloserine (DCS) exhibits a biphasic, dose-dependent pharmacological profile shaped by its partial agonism at the glycine co-agonist site of NMDA receptors and regional subunit composition. At lower doses (500 mg/day) saturate the receptor, competing with endogenous glycine and D-serine, resulting in functional antagonism, particularly at NR2A/NR2B subunits in cortical regions rich in glycine (e.g., the prefrontal cortex) 20 , 21 . At 400 mg/day, DCS likely remains within the partial agonist range but approaches the threshold (∼500 mg) at which antagonistic effects may occur, particularly in brain regions with high endogenous glycine levels (e.g., prefrontal cortex) 20 . This nonlinear dose–response is observed across neuropsychiatric conditions. In schizophrenia, low-dose DCS (50 mg/day) has been shown to reduce negative symptoms 22 , 23 , while higher doses (100–250 mg/day) have been reported to exacerbate psychotic symptoms 24 , 25 . For anxiety disorder, administering 50 mg before exposure therapy significantly enhanced fear extinction, leading to improved outcomes in both social anxiety 26 and acrophobia 27 . Similarly, in major depressive disorder, adjunctive DCS at 100 mg/day doubled remission rates when combined with transcranial magnetic stimulation (TMS) 28 . In contrast, treatment-resistant depression (TRD) may require high-dose DCS (≥1000 mg/day) to achieve efficacy, potentially through mechanisms resembling NMDA antagonism (e.g., glutamate surge, AMPA activation, BDNF upregulation), akin to ketamine’s action 29 , 30 . Thus, future studies may need to explore both higher and lower doses of DCS to identify a range where DCS may better control chronic pain. Another important consideration regarding DCS dosing in pain treatment is the region-specific dysregulation of NMDA receptors observed in chronic pain conditions. Studies have shown that chronic pain can lead to upregulation of NR2B subunits in the spinal cord and downregulation in cortical areas 31 , 32 . As a partial agonist at the glycine site of the NMDA receptor, DCS may enhance adaptive plasticity in hypoactive corticolimbic circuits but also poses a risk of overactivating hyperfunctional spinal NMDARs, potentially exacerbating nociception 33 . This dual action also underscores the critical need for precision dosing to harness DCS’s therapeutic potential while mitigating unintended amplification of maladaptive signaling. The clinical condition under investigation, cLBP, is a complex and heterogeneous disorder in which both nociceptive and neuropathic mechanisms may contribute to symptom manifestation 34 , 35 . While our preclinical studies demonstrated the efficacy of DCS in rodent models of neuropathic pain, translating these findings to cLBP entails addressing a broader and more variable pathophysiological context. Animal models of neuropathic pain often focus on evoked hypersensitivity under well-controlled conditions, whereas cLBP in humans encompasses a multifactorial etiology involving structural degeneration, inflammation, peripheral and central sensitization, and psychological comorbidities such as depression and anxiety 34 . Despite these differences, studying DCS in cLBP offers a more ecologically valid test of its clinical potential. Importantly, the promising preclinical evidence of DCS in neuropathic pain models also underscores the need to explore its therapeutic potential in other clearly defined neuropathic pain syndromes, such as diabetic neuropathy or chemotherapy-induced peripheral neuropathy, in future clinical studies. In summary, 400 mg/day DCS did not produce clinically significant effects on cLBP pain intensity or other secondary outcomes. The reason for DCS’s lack of efficacy in this trial remains unknown, but we surmise that it would be prudent to study DCS further in two different contexts. First, given DCS’s unique action as a partial NMDA receptor modulator with effects on synaptic plasticity, it may hold particular promise as an adjunctive therapy in contexts involving maladaptive learning, such as fear-avoidance, emotional dysregulation, or engagement in behavioral therapy. Second, DCS should be studied in other chronic pain syndromes, including well-defined neuropathic conditions such as diabetic neuropathy or chemotherapy-induced peripheral neuropathy. Data Availability All data produced in the present study are available upon reasonable request to the authors Acknowledgememts All authors contributed to the article and approved the submitted version. This work was funded by the Department of Defense Award # W81XWH-17–1-0426 . The authors report no financial or non-financial conflicts of interest in relation to the content of this manuscript. References 1. ↵ Collaborators GBDLBP . Global, regional, and national burden of low back pain, 1990-2020, its attributable risk factors, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021 . Lancet Rheumatol . 2023 ; 5 ( 6 ): e316 – e29 . Epub 20230522. doi: 10.1016/S2665-9913(23)00098-X . PubMed PMID: 37273833 ; PMCID: PMC10234592 . OpenUrl CrossRef PubMed 2. ↵ Dutmer AL , Schiphorst Preuper HR , Soer R , Brouwer S , Bultmann U , Dijkstra PU , Coppes MH , Stegeman P , Buskens E , van Asselt ADI , Wolff AP , Reneman MF . Personal and Societal Impact of Low Back Pain: The Groningen Spine Cohort . Spine (Phila Pa 1976) . 2019 ; 44 ( 24 ): E1443 – E51 . doi: 10.1097/BRS.0000000000003174 . PubMed PMID: 31369481 . OpenUrl CrossRef PubMed 3. Lee H , Hubscher M , Moseley GL , Kamper SJ , Traeger AC , Mansell G , McAuley JH . How does pain lead to disability? A systematic review and meta-analysis of mediation studies in people with back and neck pain . PAIN . 2015 ; 156 ( 6 ): 988 – 97 . doi: 10.1097/j.pain.0000000000000146 . PubMed PMID: 25760473 . OpenUrl CrossRef PubMed 4. ↵ Agnus Tom A , Rajkumar E , John R , Joshua George A. Determinants of quality of life in individuals with chronic low back pain: a systematic review . Health Psychol Behav Med . 2022 ; 10 ( 1 ): 124 – 44 . Epub 20220105. doi: 10.1080/21642850.2021.2022487 . PubMed PMID: 35003902 ; PMCID: PMC8741254 . OpenUrl CrossRef PubMed 5. ↵ Dieleman JL , Cao J , Chapin A , Chen C , Li Z , Liu A , Horst C , Kaldjian A , Matyasz T , Scott KW , Bui AL , Campbell M , Duber HC , Dunn AC , Flaxman AD , Fitzmaurice C , Naghavi M , Sadat N , Shieh P , Squires E , Yeung K , Murray CJL . US Health Care Spending by Payer and Health Condition, 1996-2016 . JAMA . 2020 ; 323 ( 9 ): 863 – 84 . doi: 10.1001/jama.2020.0734 . PubMed PMID: 32125402 ; PMCID: PMC7054840 . OpenUrl CrossRef PubMed 6. ↵ Kreiner DS , Matz P , Bono CM , Cho CH , Easa JE , Ghiselli G , Ghogawala Z , Reitman CA , Resnick DK , Watters WC , 3rd . , Annaswamy TM , Baisden J , Bartynski WS , Bess S , Brewer RP , Cassidy RC , Cheng DS , Christie SD , Chutkan NB , Cohen BA , Dagenais S , Enix DE , Dougherty P , Golish SR , Gulur P , Hwang SW , Kilincer C , King JA , Lipson AC , Lisi AJ , Meagher RJ , O’Toole JE , Park P , Pekmezci M , Perry DR , Prasad R , Provenzano DA , Radcliff KE , Rahmathulla G , Reinsel TE , Rich RL , Jr . ., Robbins DS , Rosolowski KA , Sembrano JN , Sharma AK , Stout AA , Taleghani CK , Tauzell RA , Trammell T , Vorobeychik Y , Yahiro AM . Guideline summary review: an evidence-based clinical guideline for the diagnosis and treatment of low back pain . Spine J . 2020 ; 20 ( 7 ): 998 – 1024 . Epub 20200422. doi: 10.1016/j.spinee.2020.04.006 . PubMed PMID: 32333996 . OpenUrl CrossRef PubMed 7. ↵ Hestbaek L , Leboeuf-Yde C , Manniche C. Low back pain: what is the long-term course? A review of studies of general patient populations . Eur Spine J . 2003 ; 12 ( 2 ): 149 – 65 . Epub 20030128. doi: 10.1007/s00586-002-0508-5 . PubMed PMID: 12709853 ; PMCID: PMC3784852 . OpenUrl CrossRef PubMed Web of Science 8. ↵ Krebs EE , Gravely A , Nugent S , Jensen AC , DeRonne B , Goldsmith ES , Kroenke K , Bair MJ , Noorbaloochi S. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial . JAMA . 2018 ; 319 ( 9 ): 872 – 82 . doi: 10.1001/jama.2018.0899 . PubMed PMID: 29509867 ; PMCID: PMC5885909 . OpenUrl CrossRef PubMed 9. ↵ White AP , Arnold PM , Norvell DC , Ecker E , Fehlings MG . Pharmacologic management of chronic low back pain: synthesis of the evidence . Spine (Phila Pa 1976) . 2011 ; 36 ( 21 Suppl ): S131 – 43 . doi: 10.1097/BRS.0b013e31822f178f . PubMed PMID: 21952185 . OpenUrl CrossRef PubMed 10. ↵ HEAL Initiative . Reducing Opioid-Related Harms to Treat Chronic Pain National Institutes of Health 2024 . Available from: https://heal.nih.gov/research/clinical-research/integrative-management-chronic-pain . 11. ↵ Schnitzer TJ , Torbey S , Herrmann K , Kaushal G , Yeasted R , Vania Apkarian A. A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain . Mol Pain . 2016 ; 12 : 174480691667862 . doi: 10.1177/1744806916678627 . OpenUrl CrossRef 12. ↵ Millecamps M , Centeno MV , Berra HH , Rudick CN , Lavarello S , Tkatch T , Apkarian AV . D-cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry . PAIN . 2007 ; 132 ( 1-2 ): 108 – 23 . Epub 20070420. doi: 10.1016/j.pain.2007.03.003 . PubMed PMID: 17449176 ; PMCID: PMC3224847 . OpenUrl CrossRef PubMed 13. ↵ Schade S , Paulus W. D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review . Int J Neuropsychopharmacol . 2016 ; 19 ( 4 ). Epub 20160420. doi: 10.1093/ijnp/pyv102 . PubMed PMID: 26364274 ; PMCID: PMC4851259 . OpenUrl CrossRef PubMed 14. ↵ Walker DL , Ressler KJ , Lu K-T , Davis M. Facilitation of Conditioned Fear Extinction by Systemic Administration or Intra-Amygdala Infusions of d-Cycloserine as Assessed with Fear-Potentiated Startle in Rats . J Neurosci . 2002 ; 22 ( 6 ): 2343 – 51 . doi: 10.1523/JNEUROSCI.22-06-02343.2002 . OpenUrl Abstract / FREE Full Text 15. ↵ Norberg MM , Krystal JH , Tolin DF . A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy . Biol Psychiatry . 2008 ; 63 ( 12 ): 1118 – 26 . Epub 20080307. doi: 10.1016/j.biopsych.2008.01.012 . PubMed PMID: 18313643 . OpenUrl CrossRef PubMed Web of Science 16. ↵ Ledgerwood L , Richardson R , Cranney J. D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement . Behav Neurosci . 2004 ; 118 ( 3 ): 505 – 13 . doi: 10.1037/0735-7044.118.3.505 . PubMed PMID: 15174928 . OpenUrl CrossRef PubMed Web of Science 17. ↵ Aupperle RL , Hale LR , Chambers RJ , Cain SE , Barth FX , Sharp SC , Denney DR , Savage CR . An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia . CNS Spectr . 2009 ; 14 ( 10 ): 556 – 71 . doi: 10.1017/s1092852900024044 . PubMed PMID: 20095368 . OpenUrl CrossRef PubMed Web of Science 18. ↵ Baliki Marwan N , Apkarian AV . Nociception, Pain, Negative Moods, and Behavior Selection . Neuron . 2015 ; 87 ( 3 ): 474 – 91 . doi: 10.1016/j.neuron.2015.06.005 . OpenUrl CrossRef PubMed 19. ↵ Schnitzer TJ , Torbey S , Herrmann K , Kaushal G , Yeasted R , Vania Apkarian A. A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain . Mol Pain . 2016 ; 12 . Epub 20161115. doi: 10.1177/1744806916678627 . PubMed PMID: 27852965 ; PMCID: PMC5117251 . OpenUrl CrossRef PubMed 20. ↵ Sheinin A , Shavit S , Benveniste M. Subunit specificity and mechanism of action of NMDA partial agonist D-cycloserine . Neuropharmacology . 2001 ; 41 ( 2 ): 151 – 8 . doi: 10.1016/s0028-3908(01)00073-9 . PubMed PMID: 11489451 . OpenUrl CrossRef PubMed Web of Science 21. ↵ Dravid SM , Burger PB , Prakash A , Geballe MT , Yadav R , Le P , Vellano K , Snyder JP , Traynelis SF . Structural determinants of D-cycloserine efficacy at the NR1/NR2C NMDA receptors . J Neurosci . 2010 ; 30 ( 7 ): 2741 – 54 . doi: 10.1523/JNEUROSCI.5390-09.2010 . PubMed PMID: 20164358 ; PMCID: PMC2862277 . OpenUrl Abstract / FREE Full Text 22. ↵ Heresco-Levy U , Javitt DC , Ermilov M , Silipo G , Shimoni J. Double-blind, placebo-controlled, crossover trial of D-cycloserine adjuvant therapy for treatment-resistant schizophrenia . Int J Neuropsychopharmacol . 1998 ; 1 ( 2 ): 131 – 5 . doi: 10.1017/S1461145798001242 . PubMed PMID: 11281957 . OpenUrl CrossRef PubMed 23. ↵ Goff DC , Cather C , Gottlieb JD , Evins AE , Walsh J , Raeke L , Otto MW , Schoenfeld D , Green MF . Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study . Schizophr Res . 2008 ; 106 ( 2-3 ): 320 – 7 . Epub 20080916. doi: 10.1016/j.schres.2008.08.012 . PubMed PMID: 18799288 ; PMCID: PMC2628436 . OpenUrl CrossRef PubMed 24. ↵ Cascella NG MF , Cavallini C , Smeraldi E. D-Cycloserine adjuvant therapy to conventional neuroleptic treatment in zchizophreania: An open-label study . Neural Transm-Gen Sect . 1994 . 25. ↵ van Berckel BN , Evenblij CN , van Loon BJ , Maas MF , van der Geld MA , Wynne HJ , van Ree JM , Kahn RS . D-cycloserine increases positive symptoms in chronic schizophrenic patients when administered in addition to antipsychotics: a double-blind, parallel, placebo-controlled study . Neuropsychopharmacology . 1999 ; 21 ( 2 ): 203 – 10 . doi: 10.1016/S0893-133X(99)00014-7 . PubMed PMID: 10432468 . OpenUrl CrossRef PubMed Web of Science 26. ↵ Hofmann SG , Pollack MH , Otto MW . Augmentation treatment of psychotherapy for anxiety disorders with D-cycloserine . CNS Drug Rev . 2006 ; 12 ( 3-4 ): 208 – 17 . doi: 10.1111/j.1527-3458.2006.00208.x . PubMed PMID: 17227287 ; PMCID: PMC2151200 . OpenUrl CrossRef PubMed Web of Science 27. ↵ Ressler KJ , Rothbaum BO , Tannenbaum L , Anderson P , Graap K , Zimand E , Hodges L , Davis M. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear . Arch Gen Psychiatry . 2004 ; 61 ( 11 ): 1136 – 44 . doi: 10.1001/archpsyc.61.11.1136 . PubMed PMID: 15520361 . OpenUrl CrossRef PubMed Web of Science 28. ↵ Cole J , Sohn MN , Harris AD , Bray SL , Patten SB , McGirr A. Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder: A Randomized Clinical Trial . JAMA Psychiatry . 2022 ; 79 ( 12 ): 1153 – 61 . doi: 10.1001/jamapsychiatry.2022.3255 . PubMed PMID: 36223114 ; PMCID: PMC9557938 . OpenUrl CrossRef PubMed 29. ↵ Heresco-Levy U , Gelfin G , Bloch B , Levin R , Edelman S , Javitt DC , Kremer I. A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression . Int J Neuropsychopharmacol . 2013 ; 16 ( 3 ): 501 – 6 . Epub 20120917. doi: 10.1017/S1461145712000910 . PubMed PMID: 23174090 . OpenUrl CrossRef PubMed 30. ↵ Kantrowitz JT , Milak MS , Mao X , Shungu DC , Mann JJ . d-Cycloserine, an NMDA Glutamate Receptor Glycine Site Partial Agonist, Induces Acute Increases in Brain Glutamate Plus Glutamine and GABA Comparable to Ketamine . Am J Psychiatry . 2016 ; 173 ( 12 ): 1241 – 2 . doi: 10.1176/appi.ajp.2016.16060735 . PubMed PMID: 27903101 . OpenUrl CrossRef PubMed 31. ↵ Qu XX , Cai J , Li MJ , Chi YN , Liao FF , Liu FY , Wan Y , Han JS , Xing GG . Role of the spinal cord NR2B-containing NMDA receptors in the development of neuropathic pain . Exp Neurol . 2009 ; 215 ( 2 ): 298 – 307 . Epub 20081112. doi: 10.1016/j.expneurol.2008.10.018 . PubMed PMID: 19046970 . OpenUrl CrossRef PubMed Web of Science 32. ↵ Ultenius C , Linderoth B , Meyerson BA , Wallin J. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat . Neurosci Lett . 2006 ; 399 ( 1-2 ): 85 – 90 . Epub 20060208. doi: 10.1016/j.neulet.2006.01.018 . PubMed PMID: 16469445 . OpenUrl CrossRef PubMed Web of Science 33. ↵ Tan-No K , Esashi A , Nakagawasai O , Niijima F , Furuta S , Sato T , Satoh S , Yasuhara H , Tadano T. Intrathecally administered D-cycloserine produces nociceptive behavior through the activation of N-methyl-D-aspartate receptor ion-channel complex acting on the glycine recognition site . J Pharmacol Sci . 2007 ; 104 ( 1 ): 39 – 45 . Epub 20070424. doi: 10.1254/jphs.fp0070203 . PubMed PMID: 17452810 . OpenUrl CrossRef PubMed Web of Science 34. ↵ Vlaeyen JWS , Maher CG , Wiech K , Van Zundert J , Meloto CB , Diatchenko L , Battie MC , Goossens M , Koes B , Linton SJ . Low back pain . Nat Rev Dis Primers . 2018 ; 4 ( 1 ): 52 . Epub 20181213. doi: 10.1038/s41572-018-0052-1 . PubMed PMID: 30546064 . OpenUrl CrossRef PubMed 35. ↵ Freynhagen R , Baron R , Gockel U , Tolle TR . painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain . Curr Med Res Opin . 2006 ; 22 ( 10 ): 1911 – 20 . doi: 10.1185/030079906X132488 . PubMed PMID: 17022849 . OpenUrl CrossRef PubMed Web of Science View the discussion thread. Back to top Previous Next Posted September 15, 2025. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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