Tolerability and Safety of a New Oral Device for Enhancing Prevention and Treatment of Oral Mucositis in a Group of Patients with Hematologic Malignancies Undergoing Chemotherapy

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An estimated 40% of patients undergoing systemic chemotherapy develop oral mucositis (OM), a major cause of morbidity in cancer patients. These are only a few options for preventing and treating OM, and these do not include FDA-registered devices. Bocaliner™ is an FDA-registered Class I medical device, designed to enhance the effects of oral topical therapies by prolonging the retention of local agents. This study examines the tolerability of the device in a group of patients with hematologic malignancies undergoing systemic chemotherapy. Methods . An initial interim analysis of data from Phase 1/Phase 2 randomized, controlled trial SPOM (Study for the Prevention of Oral Mucositis, NCT05338398) was performed. Patients with blood malignancies undergoing chemotherapy at the Yeolyan Hematology and Oncology Center (Yerevan, Armenia) were randomized into two groups after initiation of chemotherapy: benzydamine (0.15%,120mL) or saline (0.9%, 120mL) mouthwash both applied multiple times daily for 14 days after the start of the systemic treatment. Half of the patients in each study group were randomly assigned to a Bocaliner device with instructions for use immediately following each mouthwash use. Patients completed questionnaires regarding the tolerability and safety of the device on days 1 and day 14 of chemotherapy and use of the device. Results . At the time of the interim analysis, 28 patients who received oral devices had completed the study. The mean age of participants was 49 years and 14 (50%) were female. The median number of times of medical device daily use was 3, and the median duration of each use was 10 minutes. On the initial tryout of the device, 22 (71%) of patients reported tolerating it well, and 6 (29%) reported it caused some discomfort. After 14 days of use, 15 patients (35.7%) reported benefit from the device, with 6 (21.4%) of patients stating the device helped to reduce pain, 4 (14.3%) indicating that it helped them to eat, and 5 (17.8%) patients claiming both benefits. Adverse events after 14 days of use included discomfort (n=2, 7.1%), pain around the cheekbone (n=3, 10.7%), nausea (n=2, 7.1%), and increased salivation (n=1, 3.6%); none of these led to discontinuation of using the device. Eighteen (64%) participants said they would use the device again. Five patients (17.8%) developed OM during chemotherapy. Conclusions . The use of a new medical device designed to enhance oral topical medications in combination with oral topical therapy is well tolerated among patients with hematologic malignancies undergoing systemic chemotherapy. Future studies are planned to evaluate its efficacy for enhancing the prevention and/or treatment of OM with oral topical therapies. ClinicalTrials.gov ID NCT05338398, filed 2022-4-15 Figures Figure 1 Figure 2 Introduction Oral mucositis (OM) is characterized by inflammation of the mucosal lining of the mouth, causing erythema and ulcerations. The pathophysiology of OM is complex and involves mucosal cell damage, altered DNA from oxygen free radicals, enhancement of pro-inflammatory cytokines, and altered oral flora ( 1 , 2 ). Symptoms include pain, dysphagia, and dysphonia. OM is a common and serious complication of chemotherapy and radiation therapy. Patients with severe OM may require opioid medications for pain, and hospitalization for fluid and nutritional support ( 3 , 4 ). Oral mucositis negatively impacts the quality of life in patients receiving cancer treatment. When severe, oral mucositis may require patients to delay or discontinue their treatment for cancer ( 4 ). Oral mucositis occurs in about 40% of all patients receiving chemotherapy ( 4 , 5 ) and in 80% of patients receiving hematopoietic stem cell transplantation ( 6 ). The Multinational Association for Supportive Care in Cancer (MASCC) developed guidelines for preventing and treating oral mucositis ( 7 ). Preventive measures that may be effective include basic oral care, anti-inflammatory agents, intraoral photo biomodulation, cryotherapy, and intravenous growth factors. Oral topical applications (e.g., gels, rinses, and mouthwashes) are usually swished in the mouth and then expectorated or swallowed. The dwell time of oral topical medications within the oral cavity is very short ( 8 ). This brief period inside the mouth likely limits their analgesic or healing effects on the oral mucosa. The clearance of the active components of these medications from the oral mucosa is facilitated by ongoing dilution by the saliva, movements of mouth muscles, and swallowing ( 9 , 10 ). The combined effects of these factors further limit the efficacy of oral topical medications on the oral mucosa. A novel silicone-based orally inserted medical device called Bocaliner™ was engineered to enhance the retention of oral topical therapies in patients with oral mucosal diseases including oral mucositis. The device is inserted into the mouth immediately after either expectoration or swallowing oral topical medicines. Based on its design and initial studies, the device keeps local treatments in the mouth longer at higher concentrations by reducing salivary dilution, covering a portion of the surface of the oral mucosa, and holding the mouth still (Fig. 1 ). A proof-of-concept study has demonstrated that Bocaliner™ prolongs the concentration and duration of a topical polymer remains within the oral cavity and increases the area under the curve of an ETOH marker concentration (mixed with the polymer) versus the time curve ( 8 ). The effects should theoretically lead to better clinical outcomes in people who are at risk of developing oral mucositis, such as patients undergoing chemotherapy. In this study, we aimed to understand the safety profile of the new oral medical device in patients undergoing chemotherapeutic treatment for the established diagnosis of blood malignancy. Methods Study Design Study for the Prevention of Oral Mucositis (SPOM) is a Phase I/Phase II single-center randomized controlled trial conducted at the Yeolyan Hematology and Oncology Center in Yerevan, Armenia ( https://www.clinicaltrials.gov/study/NCT05338398 ). Adult patients with established hematologic malignancies receiving systemic chemotherapy were randomly assigned to receive either benzydamine mouthwash or saline mouthwash 3–5 times a day for 14 days since the initiation of chemotherapy. The goal of the Phase II study was to determine whether topical benzydamine mouthwash was superior in preventing chemotherapy-induced oral mucositis compared to standard methods, which include oral rinses with saline. The Phase I portion of the study was designed to demonstrate the tolerability of Bocaliner™ the first time the device was placed in the mouth and its tolerability and safety after 14 days of use following initiation of chemotherapy. Randomization The SPOM trial utilized a block randomization with two strata for gender and the use of Bocaliner. Each block was initially randomized to either a control treatment with saline rinses or an investigational treatment with benzydamine oral mouthwash. Each block consisted of four subjects with a 1:1 allocation of men and women. The subjects were further randomized to receive the assigned treatment adjunct with the Bocaliner™ device or not. All patients in the study received treatments for 14 days. Per protocol, results of the Phase I portion are analyzed independently from the Phase II results. Interventions As per randomization, patients received one of the two mouthwashes: benzydamine (0.15%, 120mL) or saline (0.9%, 120mL) 3 to 5 times a day each time during the first 14 days since the initiation of a systemic chemotherapy regimen. Half of each treatment group further received Bocaliner mouthwash as an adjunct to the main prevention strategy. The device was instructed to be inserted right after the use of the mouthwash for 5 to 20 minutes. Patients who were assigned to use Bocaliner had to complete two questionnaires. The first questionnaire was administered at the initial visit after a brief trout (5 minutes) of the medical device (Bocaliner Tryout Questionnaire - See Appendix A). The second questionnaire was administered after using Bocaliner™ for 14 days (Follow-up Bocaliner Questionnaire - See Appendix B). Patient Population Inclusion and Exclusion Criteria Patients aged 18 years and older with diagnosed hematologic malignancies receiving systemic chemotherapy at the Yeolyan Hematology and Oncology Center were invited to participate in the SPOM trial. Participants should have been willing to use study materials (i.e., benzydamine or saline mouthwashes as well as Bocaliner™, as per randomization) to complete initial and follow-up questionnaires. All patients included in the study must have signed informed consent upon a detailed description of the conducted study provided by one of the research team members. Exclusion Criteria: Patients were excluded from the study if they had oral or maxillofacial disorders under treatment, systemic disease affecting oral mucosa, recurrent oral lesions from conditions other than oral mucositis, current use of medications affecting salivation (cholinomimetics, anticholinergic agents), concurrent or previous radiotherapy, inability or unwillingness to wear Bocaliner™ for the study period, known intolerance to silicone materials or to benzydamine or any component of the mouthwash formulations. Individuals with significant difficulties communicating and understanding as well as those who refused to sign informed consent were also not considered for the inclusion in the SPOM trial. Outcomes measured for the Phase 1 Clinical Trial: Patient reported outcomes were measured based on the following: Completed questionnaires for tolerability of an orally inserted Bocaliner™ device the first time that it was placed in the mouth. Safety and tolerability of using Bocaliner™ combined with oral topical treatments after 14 days of use following initiation of chemotherapy. Data Analysis Socio-demographic data relevant to the study outcomes was collected from all participants. All data collected for the Phase I clinical trial was analyzed using descriptive analysis. Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Center of Medical Genetics And Primary Health Care. Results At the time of the interim analysis, twenty-eight patients who used the oral device had completed the study. Thirteen patients received treatment with benzydamine mouthwash, while 15 patients were assigned to saline mouthwash. The clinical characteristics of patients receiving Bocaliner are presented in Table 1 . The mean age of the patients receiving Bocaliner was 49 years, and 14 (50%) were female. The median number of times per day that the mouthwash combined with Bocaliner was used was 3. The median duration that Bocaliner was retained in the mouth during each use was 10 minutes. Table 1 Characteristics of patients from the SPOM trial assigned to the oral device Patient Characteristics Benzydamine Saline All Participants (n) 13 15 28 Mean age (years) 50.2 51.5 49.1 Female (%) 6(46) 8 (53) 14 (50) BMI (kg/m 2 ) 25.4 24.9 25.0 Smoking status (current, former) 4 formers 2 formers 4 currents 6 formers 4 currents Alcohol use (yes/no) 1/13 1/15 2/28 Marital status 3 unmarried 10 married 2 unmarried 13 married 5 unmarried 23 married Primary hemato-oncologic diagnosis ALL ( 5 ) AML ( 4 ) DLBCL ( 2 ) CNS lymphoma MM AML ( 4 ) HL ( 3 ) MM ( 3 ) ALL ( 2 ) Burkitt lymphoma CNS lymphoma MDS AML ( 8 ) ALL ( 7 ) MM ( 4 ) HL ( 3 ) NHL ( 3 ) CNS lymphoma ( 2 ) MDS ( 1 ) Previous oral mucositis (yes/no) 3 2 5 Oral mucositis during study (yes/no) 2 3 5 Prosthesis (yes/no) 3 5 8 Recent interventions (yes/no) 7 4 11 Bone marrow transplant (yes/no) 0 1 1 ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CNS: central nervous system; DLBCL: diffuse large B-cell lymphoma; HL: Hodgkin lymphoma; MDS: myelodysplastic syndrome; MM: multiple myeloma; NHL: non-Hodgkin lymphoma. On the initial tryout of the device, 22 (78.6%) of patients referred to their experience wearing the device overall as satisfactory. Particularly, 11 (39.3%) patients said it was “tolerable”, eight (n = 8, 28.6%) patients called their experience “good”, and 3 (10.7%) as “very comfortable”. Six other patients (21.4%) did not like their experience. Four patients (14.3%) reported it as “somewhat uncomfortable” and another two individuals (7.1%) said it was “uncomfortable” (Fig. 2 ). Reported adverse events after 14 days of use included discomfort while wearing the device (n = 2, 7.1%), pain around the cheekbone (n = 3, 10.7%), nausea (n = 2, 7.1%), and increased salivation in 1 (3.6%); none of which led to discontinuation of using the device Eighteen (64%) participants reported that they would use the device again if suggested by their physicians, and 10 patients (36%) said they would not use the device for the next time. Five patients (17.8%) (n = 2 in benzydamine, n = 3 in saline groups, respectively) eventually developed OM during chemotherapy. OM occurred from day 3 to day 14 after the initiation of the therapy. One of the patients in the benzydamine group had Grade III OM, while four subjects had Grade I OM, (n = 3 in the saline group and n = 1 in the benzydamine group). All cases of OM were resolved within 3 weeks from the day of development. None of the 28 patients enrolled in the trial dropped out or discontinued their treatments because of the side effects. Moreover, all of them completed the assigned study interventions, while three subjects continued to use the medical device completing the study. Using any study interventions (i.e., mouthwashes or oral devices) did not preclude the main treatment of hematologic malignancy. Four patients (14.3%) stated that the device helped them to eat during chemotherapy, while six other patients (21.4%) said the device reduced the pain they perceived related to chemotherapy, and another five patients (17.8%) said the device helped them eat and reduced pain. Five other participants (17.8%) claimed that the device helped them to perform their rinses regularly. The five patients who eventually developed OM discontinued the use of the medical device. Discussion This Phase 1 study demonstrates that a new medical device designed to enhance oral topical therapy is generally well tolerated among patients with hematologic malignancies receiving chemotherapy. After fourteen days of use, more than half of patients reported some subjective benefit from the application of the device, while 78.6% of participants were satisfied with their overall experience with the device. Less than a third of participants experienced any adverse event, all of which were self-limited and did not prompt discontinuation of the treatment. More than half of users said that they would use the device again if offered by their physicians. Considering the impact of OM on the health and well-being of affected patients, identifying appropriate treatments for the prevention of OM remains a high priority ( 11 ). Current strategies have somewhat limited efficacy ( 12 ). For example, palifermin – a recombinant keratinocyte growth factor that induces epithelial cell proliferation and differentiation – is recommended for patients undergoing autologous HCT; however, its prevention efficacy for other population groups is uncertain ( 13 ). The benefits of palifermin also come at a high cost of medication and side effects including taste disturbance ( 12 ). Photobiomodulation utilizing low-level laser therapy is another strategy that is effective in reducing the incidence of OM in patients undergoing HCT ( 14 ). Nonetheless, this technology requires expensive equipment and is thus not widely used around the world ( 14 ). The most common effective method of preventing OM to date is cryotherapy ( 12 ). This can be administered in two different ways, both of which work via reduction of the blood flow to the mucosal cells (through hypothermia-induced vasoconstriction) leading to low concentrations of the cytotoxic agents in the mouth ( 16 ). The least expensive and easiest cryotherapy option is using ice chips or ice cubes. These are swished inside of the mouth for around 30 minutes. This method has the advantage of low cost, low toxicity, and simplicity of use ( 17 ). The tolerability of ice chips is patient dependent as sensitivity to ice and cold varies from individual to individual ( 18 ). An alternative option for cryotherapy is an intraoral cooling system, which comes at a higher cost and complexity without proven benefits ( 19 ). Several topical agents were suggested for reducing the likelihood of OM development with uncertain effectiveness, including mucosal protective agents ( 20 , 21 ), steroids ( 22 ), Vitamin E ( 23 ), or honey ( 7 ). Sucralfate ( 24 ) and glutamine ( 25 ) were not shown to be effective for OM prevention. Benzydamine – an anti-inflammatory agent (not available in the US) – is recommended for the prevention of radiotherapy and chemoradiotherapy-induced OM, particularly in patients with head and neck cancer ( 26 ), although data regarding chemotherapy-induced OM is lacking. Over-the-counter oral solutions containing a combination of analgesics, anti-inflammatory, and mucosal protective compounds are frequently used and prescribed for protection from mucositis ( 29 ), although their clinical efficacy also remains uncertain ( 30 ). These recommendations, however, are given for specific patient populations, such as those undergoing autologous hematopoietic stem-cell transplantation or individuals with head and neck cancer undergoing radiotherapy or combined radio-chemotherapy ( 7 ). One likely cause of the failure of oral topical medications to significantly impact OM is that the mouth has unique pharmacokinetic properties that limit mucosal exposure to the active ingredients of these medications. Topical medications such as mouthwashes and rinses are generally swished and swallowed or expectorated after 60–120 seconds. Like topically applied gels, the active ingredients that remain attached to the oral mucosa are responsible for the action of the medication ( 9 , 10 , 27 ). However, the portion of the medication that remains adherent to the mucosal surface after swallowing or expectoration is subject to rapid clearing. This occurs from salivary dilution, mouth movement, and swallowing ( 28 ). Using a novel testing methodology, our group has demonstrated rapid clearance of a gel from the oral cavity, often within a few minutes ( 8 ). Based on these properties, a device that enhances the oral retention of oral topical medications is hypothesized to improve their efficacy. Bocaliner™ is a soft, pliable orally inserted device that is designed to increase the oral resonance time to topical medications. A prior proof of concept study of an oral gel (alginate) showed that Bocaliner increased the concentration and duration of oral retention of alginate mixed with an ETOH marker ( 8 ). It is hypothesized that the increased area under the curve of oral concentration versus the time curves of an alginate gel reflects the intrinsic properties of the device. Bocaliner is designed to provide a cover over portions of the oral mucosa, covers the parotid gland and some submandibular gland ostia, and keeps the mouth still during use ( 8 ). The results of this Phase 1 portion of the SPOM trial showed that the new medical device is tolerated among patients with hematologic malignancies for two weeks since the start of chemotherapy when using it with either benzydamine or saline mouthwash. No specific differences in the outcomes were observed with the concomitant application of either topical medication. The latter implies that the device can be safely used with different local treatment options. Although 29% of participants had some degree of side effects, most of them were self-limited and none of them were serious enough to drop out or stop the cancer treatment. It is yet unknown whether the adjunctive use of the device leads to better outcomes in terms of reduction of OM rates, decrease in grade of and symptomatology related to OM, and shortening of OM duration. In conclusion, analysis of the Phase 1 data collected as part of a Phase 1/Phase 2 clinical trial indicates that a new medical device designed to increase the oral dwell time of active ingredients in oral topical medications was well tolerated in a group of patients with hematologic malignancies undergoing systemic chemotherapy. Future research is needed to define optimal strategies for the prevention of chemotherapy-induced OM. Strengths and limitations Our study has some important limitations. Several variables (e.g., basic oral care level, dosage and intensity of chemotherapeutic agents, number of previously received treatments, and stage of the disease) were not assessed, which could have potentially influenced the results. The outcomes demonstrating the tolerability and safety of the device were based on questionnaires filled out by patients, which reflected their subjective experience with the device. It was also not possible to examine how compliant and consistent patients were with their preventive treatment for OM. Lastly, this study employed a descriptive analysis, which further limits the interpretation and generalizability of the results. We believe that these limitations are balanced by strengths. Our study used patient-reported outcomes implemented in real-world clinical settings, which were not changed or adjusted by the study design. Patients continued to receive their management as usual despite their use of the intervention, and no patient stopped their treatment because of it. Furthermore, physicians managing participants’ diseases had minimal influence on patients' reports regarding the use of the device. Declarations Conflict of Interest Eli D. Ehrenpreis MD, AGAF, FACG Dr. Eli D. Ehrenpreis is the CEO and scientific advisor for E2Bio Life Sciences and is the inventor of Bocaliner™. Competing Interests Eli D Ehrenpreis MD is the inventor of Bocaliner and CEO of E2Bio Life Sciences, LLC, the company providing funding for this study. Funding This study was funded by E2Bio Life Sciences, LLC, the inventors and developers of Bocaliner™. Author Contribution AO, LH, AV, YH, MG and EDE were involved in the initial planning and design of the study. AO, YH, and EDE were involved with entering the study on the clinicaltrials.gov database. AO and YH were involved in preparing paperwork for the institutional analysis of the protocol. AO, LH, AV, NM, MB, MG, TO, SM, RP, NG and YH were involved in subject recruitment, study implementation in Armenia, data collection, and clinical follow-up of study subjects. AO and YH performed data analysis and initial manuscript preparation. AO completed the manuscript. All authors reviewed the manuscript. Acknowledgement The authors wish to acknowledge the following individuals for their assistance with this study.Hasmik Oseyan, Levon Evoyan, Armine Farmazyan, Amalya Chakhoyan, Hayk Grigoryan, Anahit Ter-Grigoryan, Anna Sevoyan, Avetis Gharibyan, Anahit Aynajyan, Karapet Hakobyan, Martin Nubaryan, Seda Dabaghyan, and Arsene Mekinian. The authors also wish to acknowledge Dr. Joel Epstein for his advice on study design and implementation. Data Availability Data provided in this study will be made available to interested researchers. References Colella G, Boschetti CE, Vitagliano R, Colella C, Jiao L, King-Smith N, Li C, Nuoh Lau Y, Lai Z, Mohammed AI, Cirillo N. Interventions for the Prevention of Oral Mucositis in Patients Receiving Cancer Treatment: Evidence from Randomised Controlled Trials. Curr Oncol. 2023 Jan 10;30(1):967-980. doi: 10.3390/curroncol30010074. PMID: 36661723; PMCID: PMC9858113. Sonis ST. 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Anticancer research. 2001 Sep 1;21(5):3707-10. Okuno SH, Woodhouse CO, Loprinzi CL, Sloan JA, LaVasseur BI, Clemens-Schutjer D, Swan D, Axvig C, Ebbert LP, Tirona MR, Michalak JC. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. American journal of clinical oncology. 1999 Jun 1;22(3):258-61. Nicolatou-Galitis O, Bossi P, Orlandi E, Bensadoun RJ. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Supportive Care in Cancer. 2021 Oct;29:5701-9. Daugelaite G, Uzkuraityte K, Jagelaviciene E, Filipauskas A. Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis. Medicina (Kaunas). 2019 Jan 22;55(2):25. doi: 10.3390/medicina55020025. Varoni EM, Molteni A, Sardella A, Carrassi A, Di Candia D, Gigli F, Lodi F, Lodi G. Pharmacokinetics study about topical clobetasol on oral mucosa. J Oral Pathol Med. 2012 Mar;41(3):255-60. doi: 10.1111/j.1600-0714.2011.01087.x. Epub 2011 Sep 22. PMID: 21950548. Chan A, Ignoffo RJ. Survey of topical oral solutions for the treatment of chemo-induced oral mucositis. J Oncol Pharm Pract. 2005 Dec;11(4):139-43. doi: 10.1191/1078155205jp166oa. PMID: 16595065. Sio TT, Le-Rademacher JG, Leenstra JL, Loprinzi CL, Rine G, Curtis A, Singh AK, Martenson JA Jr, Novotny PJ, Tan AD, Qin R, Ko SJ, Reiter PL, Miller RC. Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial. JAMA. 2019 Apr 16;321(15):1481-1490. doi: 10.1001/jama.2019.3504. PMID: 30990550; PMCID: PMC6484809. Additional Declarations Competing interest reported. Eli D Ehrenpreis MD is the inventor of Bocaliner and CEO of E2Bio Life Sciences, LLC, the company providing funding for this study. Supplementary Files Appendix.docx Cite Share Download PDF Status: Published Journal Publication published 31 Jul, 2025 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Revision requested 19 Jan, 2025 Reviews received at journal 19 Jan, 2025 Reviews received at journal 17 Jan, 2025 Reviewers agreed at journal 09 Jan, 2025 Reviewers agreed at journal 08 Jan, 2025 Reviewers agreed at journal 13 Sep, 2024 Reviewers invited by journal 11 Sep, 2024 Editor assigned by journal 10 Sep, 2024 Submission checks completed at journal 31 Jul, 2024 First submitted to journal 26 Jul, 2024 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. 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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-4810150","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":334479119,"identity":"5160385c-fecc-4a79-b098-9f310baa70f9","order_by":0,"name":"Artem Oganesyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Artem","middleName":"","lastName":"Oganesyan","suffix":""},{"id":334479120,"identity":"f6b8f1ac-6659-4e5a-8055-1adcd5bcc05d","order_by":1,"name":"Lusine Harutyunyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Lusine","middleName":"","lastName":"Harutyunyan","suffix":""},{"id":334479121,"identity":"93a2380b-5d4a-4bda-a29f-8ff8722cbf81","order_by":2,"name":"Araksya Vanoyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Araksya","middleName":"","lastName":"Vanoyan","suffix":""},{"id":334479122,"identity":"09e765a5-0ccb-43ec-a7f4-a0e6712f0e17","order_by":3,"name":"Nare Martirosyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Nare","middleName":"","lastName":"Martirosyan","suffix":""},{"id":334479123,"identity":"e5b43e56-4c83-4464-99f0-ce1e4560709f","order_by":4,"name":"Maria Badikyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Badikyan","suffix":""},{"id":334479124,"identity":"8cc9b90e-8aea-46d4-b622-9c8035ff0e2f","order_by":5,"name":"Mark Gregory","email":"","orcid":"","institution":"Wayne State University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Gregory","suffix":""},{"id":334479125,"identity":"b9293cf4-9205-42d3-8913-62408b05d31a","order_by":6,"name":"Tigran Oganesyan","email":"","orcid":"","institution":"BIL Armenia, Healthcare Students’ Association of Armenia","correspondingAuthor":false,"prefix":"","firstName":"Tigran","middleName":"","lastName":"Oganesyan","suffix":""},{"id":334479126,"identity":"feaec2e8-032b-4b8a-9245-a58657172fe2","order_by":7,"name":"Satenik Muradyan","email":"","orcid":"","institution":"BIL Armenia, Healthcare Students’ Association of Armenia","correspondingAuthor":false,"prefix":"","firstName":"Satenik","middleName":"","lastName":"Muradyan","suffix":""},{"id":334479127,"identity":"8f116a5b-1ab4-4878-aff9-6f3fdc9b38b5","order_by":8,"name":"Razmik Petrosyan","email":"","orcid":"","institution":"BIL Armenia, Healthcare Students’ Association of Armenia","correspondingAuthor":false,"prefix":"","firstName":"Razmik","middleName":"","lastName":"Petrosyan","suffix":""},{"id":334479129,"identity":"ab461988-b8d9-49b7-8fa2-4390fe05729e","order_by":9,"name":"Nerses Ghahramanyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Nerses","middleName":"","lastName":"Ghahramanyan","suffix":""},{"id":334479132,"identity":"bf87c2a0-b401-4d8e-84ad-817a5d4ac0fd","order_by":10,"name":"Eli D. Ehrenpreis","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBAC+3bGBuafDVBeAoMNA4MEAS0GzEAtjAgtacRoYWBAaGFgOEyMFmagLTvuyZlL9z588ODPeXn+2Q2Mjyt+4dZiD3LYxzPFxpZzjhsbJLbdNpxx5wCz4dk+Qn5pS0jccCONTSKx4TZjw40ENsnGHsJa6oFa2H8k/DlnP59YLQkGQFsYEtgOAK0Damn4gV/LYaAWww13jjFLJLYlJ2+8kdhs2NiAx/vt7Q8f/2xLkDe43cb48ccfO9t5N5IPPmz4g1sLCBwAk4joAEYTYxt+LQxoWkCAgC2jYBSMglEwogAA5mZVJOjkPrEAAAAASUVORK5CYII=","orcid":"","institution":"Advocate Lutheran General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Eli","middleName":"D.","lastName":"Ehrenpreis","suffix":""},{"id":334479136,"identity":"c71f37b7-ebcc-4a38-82de-6e21594ead55","order_by":11,"name":"Yervand Hakobyan","email":"","orcid":"","institution":"National Institute of Health","correspondingAuthor":false,"prefix":"","firstName":"Yervand","middleName":"","lastName":"Hakobyan","suffix":""}],"badges":[],"createdAt":"2024-07-26 20:53:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4810150/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4810150/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-025-09722-0","type":"published","date":"2025-07-31T16:38:10+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":64008705,"identity":"235933a5-6c86-4504-8bda-f2834869e1ec","added_by":"auto","created_at":"2024-09-04 23:06:39","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":143040,"visible":true,"origin":"","legend":"\u003cp\u003eOral medical device (Bocaliner™) is inserted into the mouth for 5-30 minutes after rinsing and expectorating or swallowing an oral topical treatment.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4810150/v1/e1cb9a720c20a2ac11670163.jpeg"},{"id":64008706,"identity":"4f564edd-3df7-4b9d-956e-4989f0c802a7","added_by":"auto","created_at":"2024-09-04 23:06:39","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":141770,"visible":true,"origin":"","legend":"\u003cp\u003eResult of the first tryout of the novel oral medical device\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4810150/v1/f3198e1947e32d67c3d93d9d.jpeg"},{"id":88268449,"identity":"c65cd320-e921-4775-9fec-a99de3718500","added_by":"auto","created_at":"2025-08-04 16:51:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":946093,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4810150/v1/19eb69f3-6d8e-4fa6-942c-18b02798e38f.pdf"},{"id":64008707,"identity":"9b5bd0a6-7929-4e00-963b-205ff452a645","added_by":"auto","created_at":"2024-09-04 23:06:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16720,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-4810150/v1/8f6893be93ab8ea2edcd886c.docx"}],"financialInterests":"Competing interest reported. Eli D Ehrenpreis MD is the inventor of Bocaliner and CEO of E2Bio Life Sciences, LLC, the company providing funding for this study.","formattedTitle":"Tolerability and Safety of a New Oral Device for Enhancing Prevention and Treatment of Oral Mucositis in a Group of Patients with Hematologic Malignancies Undergoing Chemotherapy","fulltext":[{"header":"Introduction","content":"\u003cp\u003e Oral mucositis (OM) is characterized by inflammation of the mucosal lining of the mouth, causing erythema and ulcerations. The pathophysiology of OM is complex and involves mucosal cell damage, altered DNA from oxygen free radicals, enhancement of pro-inflammatory cytokines, and altered oral flora (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Symptoms include pain, dysphagia, and dysphonia. OM is a common and serious complication of chemotherapy and radiation therapy. Patients with severe OM may require opioid medications for pain, and hospitalization for fluid and nutritional support (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Oral mucositis negatively impacts the quality of life in patients receiving cancer treatment. When severe, oral mucositis may require patients to delay or discontinue their treatment for cancer (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOral mucositis occurs in about 40% of all patients receiving chemotherapy (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) and in 80% of patients receiving hematopoietic stem cell transplantation (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The Multinational Association for Supportive Care in Cancer (MASCC) developed guidelines for preventing and treating oral mucositis (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Preventive measures that may be effective include basic oral care, anti-inflammatory agents, intraoral photo biomodulation, cryotherapy, and intravenous growth factors.\u003c/p\u003e \u003cp\u003e Oral topical applications (e.g., gels, rinses, and mouthwashes) are usually swished in the mouth and then expectorated or swallowed. The dwell time of oral topical medications within the oral cavity is very short (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This brief period inside the mouth likely limits their analgesic or healing effects on the oral mucosa. The clearance of the active components of these medications from the oral mucosa is facilitated by ongoing dilution by the saliva, movements of mouth muscles, and swallowing (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The combined effects of these factors further limit the efficacy of oral topical medications on the oral mucosa.\u003c/p\u003e \u003cp\u003eA novel silicone-based orally inserted medical device called Bocaliner\u0026trade; was engineered to enhance the retention of oral topical therapies in patients with oral mucosal diseases including oral mucositis. The device is inserted into the mouth immediately after either expectoration or swallowing oral topical medicines. Based on its design and initial studies, the device keeps local treatments in the mouth longer at higher concentrations by reducing salivary dilution, covering a portion of the surface of the oral mucosa, and holding the mouth still (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). A proof-of-concept study has demonstrated that Bocaliner\u0026trade; prolongs the concentration and duration of a topical polymer remains within the oral cavity and increases the area under the curve of an ETOH marker concentration (mixed with the polymer) versus the time curve (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). The effects should theoretically lead to better clinical outcomes in people who are at risk of developing oral mucositis, such as patients undergoing chemotherapy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn this study, we aimed to understand the safety profile of the new oral medical device in patients undergoing chemotherapeutic treatment for the established diagnosis of blood malignancy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eStudy for the Prevention of Oral Mucositis (SPOM) is a Phase I/Phase II single-center randomized controlled trial conducted at the Yeolyan Hematology and Oncology Center in Yerevan, Armenia (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.clinicaltrials.gov/study/NCT05338398\u003c/span\u003e\u003cspan address=\"https://www.clinicaltrials.gov/study/NCT05338398\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). Adult patients with established hematologic malignancies receiving systemic chemotherapy were randomly assigned to receive either benzydamine mouthwash or saline mouthwash 3\u0026ndash;5 times a day for 14 days since the initiation of chemotherapy. The goal of the Phase II study was to determine whether topical benzydamine mouthwash was superior in preventing chemotherapy-induced oral mucositis compared to standard methods, which include oral rinses with saline. The Phase I portion of the study was designed to demonstrate the tolerability of Bocaliner\u0026trade; the first time the device was placed in the mouth and its tolerability and safety after 14 days of use following initiation of chemotherapy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eRandomization\u003c/h2\u003e \u003cp\u003eThe SPOM trial utilized a block randomization with two strata for gender and the use of Bocaliner. Each block was initially randomized to either a control treatment with saline rinses or an investigational treatment with benzydamine oral mouthwash. Each block consisted of four subjects with a 1:1 allocation of men and women. The subjects were further randomized to receive the assigned treatment adjunct with the Bocaliner\u0026trade; device or not. All patients in the study received treatments for 14 days. Per protocol, results of the Phase I portion are analyzed independently from the Phase II results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInterventions\u003c/h2\u003e \u003cp\u003eAs per randomization, patients received one of the two mouthwashes: benzydamine (0.15%, 120mL) or saline (0.9%, 120mL) 3 to 5 times a day each time during the first 14 days since the initiation of a systemic chemotherapy regimen. Half of each treatment group further received Bocaliner mouthwash as an adjunct to the main prevention strategy. The device was instructed to be inserted right after the use of the mouthwash for 5 to 20 minutes.\u003c/p\u003e \u003cp\u003ePatients who were assigned to use Bocaliner had to complete two questionnaires. The first questionnaire was administered at the initial visit after a brief trout (5 minutes) of the medical device (Bocaliner Tryout Questionnaire - See Appendix A). The second questionnaire was administered after using Bocaliner\u0026trade; for 14 days (Follow-up Bocaliner Questionnaire - See Appendix B).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient Population\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003e Patients aged 18 years and older with diagnosed hematologic malignancies receiving systemic chemotherapy at the Yeolyan Hematology and Oncology Center were invited to participate in the SPOM trial. Participants should have been willing to use study materials (i.e., benzydamine or saline mouthwashes as well as Bocaliner\u0026trade;, as per randomization) to complete initial and follow-up questionnaires. All patients included in the study must have signed informed consent upon a detailed description of the conducted study provided by one of the research team members.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eExclusion Criteria:\u003c/h2\u003e \u003cp\u003ePatients were excluded from the study if they had oral or maxillofacial disorders under treatment, systemic disease affecting oral mucosa, recurrent oral lesions from conditions other than oral mucositis, current use of medications affecting salivation (cholinomimetics, anticholinergic agents), concurrent or previous radiotherapy, inability or unwillingness to wear Bocaliner\u0026trade; for the study period, known intolerance to silicone materials or to benzydamine or any component of the mouthwash formulations. Individuals with significant difficulties communicating and understanding as well as those who refused to sign informed consent were also not considered for the inclusion in the SPOM trial.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes measured for the Phase 1 Clinical Trial:\u003c/h2\u003e \u003cp\u003ePatient reported outcomes were measured based on the following:\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e Completed questionnaires for tolerability of an orally inserted Bocaliner\u0026trade; device the first time that it was placed in the mouth.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eSafety and tolerability of using Bocaliner\u0026trade; combined with oral topical treatments after 14 days of use following initiation of chemotherapy.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eSocio-demographic data relevant to the study outcomes was collected from all participants. All data collected for the Phase I clinical trial was analyzed using descriptive analysis.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003e This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Center of Medical Genetics And Primary Health Care.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e At the time of the interim analysis, twenty-eight patients who used the oral device had completed the study. Thirteen patients received treatment with benzydamine mouthwash, while 15 patients were assigned to saline mouthwash. The clinical characteristics of patients receiving Bocaliner are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of the patients receiving Bocaliner was 49 years, and 14 (50%) were female. The median number of times per day that the mouthwash combined with Bocaliner was used was 3. The median duration that Bocaliner was retained in the mouth during each use was 10 minutes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients from the SPOM trial assigned to the oral device\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenzydamine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSaline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParticipants (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean age (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status (current, former)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 formers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 formers\u003c/p\u003e \u003cp\u003e4 currents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 formers\u003c/p\u003e \u003cp\u003e4 currents\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol use (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1/15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 unmarried\u003c/p\u003e \u003cp\u003e10 married\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 unmarried\u003c/p\u003e \u003cp\u003e13 married\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 unmarried\u003c/p\u003e \u003cp\u003e23 married\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary hemato-oncologic diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eALL (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAML (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDLBCL (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCNS lymphoma\u003c/p\u003e \u003cp\u003eMM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAML (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHL (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMM (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eALL (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eBurkitt lymphoma\u003c/p\u003e \u003cp\u003eCNS lymphoma\u003c/p\u003e \u003cp\u003eMDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAML (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eALL (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMM (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHL (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eNHL (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCNS lymphoma (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMDS (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious oral mucositis (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral mucositis during study (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProsthesis (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecent interventions (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone marrow transplant (yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CNS: central nervous system; DLBCL: diffuse large B-cell lymphoma; HL: Hodgkin lymphoma; MDS: myelodysplastic syndrome; MM: multiple myeloma; NHL: non-Hodgkin lymphoma.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOn the initial tryout of the device, 22 (78.6%) of patients referred to their experience wearing the device overall as satisfactory. Particularly, 11 (39.3%) patients said it was \u0026ldquo;tolerable\u0026rdquo;, eight (n\u0026thinsp;=\u0026thinsp;8, 28.6%) patients called their experience \u0026ldquo;good\u0026rdquo;, and 3 (10.7%) as \u0026ldquo;very comfortable\u0026rdquo;. Six other patients (21.4%) did not like their experience. Four patients (14.3%) reported it as \u0026ldquo;somewhat uncomfortable\u0026rdquo; and another two individuals (7.1%) said it was \u0026ldquo;uncomfortable\u0026rdquo; (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eReported adverse events after 14 days of use included discomfort while wearing the device (n\u0026thinsp;=\u0026thinsp;2, 7.1%), pain around the cheekbone (n\u0026thinsp;=\u0026thinsp;3, 10.7%), nausea (n\u0026thinsp;=\u0026thinsp;2, 7.1%), and increased salivation in 1 (3.6%); none of which led to discontinuation of using the device\u003c/p\u003e \u003cp\u003eEighteen (64%) participants reported that they would use the device again if suggested by their physicians, and 10 patients (36%) said they would not use the device for the next time. Five patients (17.8%) (n\u0026thinsp;=\u0026thinsp;2 in benzydamine, n\u0026thinsp;=\u0026thinsp;3 in saline groups, respectively) eventually developed OM during chemotherapy. OM occurred from day 3 to day 14 after the initiation of the therapy. One of the patients in the benzydamine group had Grade III OM, while four subjects had Grade I OM, (n\u0026thinsp;=\u0026thinsp;3 in the saline group and n\u0026thinsp;=\u0026thinsp;1 in the benzydamine group). All cases of OM were resolved within 3 weeks from the day of development.\u003c/p\u003e \u003cp\u003eNone of the 28 patients enrolled in the trial dropped out or discontinued their treatments because of the side effects. Moreover, all of them completed the assigned study interventions, while three subjects continued to use the medical device completing the study. Using any study interventions (i.e., mouthwashes or oral devices) did not preclude the main treatment of hematologic malignancy.\u003c/p\u003e \u003cp\u003eFour patients (14.3%) stated that the device helped them to eat during chemotherapy, while six other patients (21.4%) said the device reduced the pain they perceived related to chemotherapy, and another five patients (17.8%) said the device helped them eat and reduced pain. Five other participants (17.8%) claimed that the device helped them to perform their rinses regularly. The five patients who eventually developed OM discontinued the use of the medical device.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis Phase 1 study demonstrates that a new medical device designed to enhance oral topical therapy is generally well tolerated among patients with hematologic malignancies receiving chemotherapy. After fourteen days of use, more than half of patients reported some subjective benefit from the application of the device, while 78.6% of participants were satisfied with their overall experience with the device. Less than a third of participants experienced any adverse event, all of which were self-limited and did not prompt discontinuation of the treatment. More than half of users said that they would use the device again if offered by their physicians.\u003c/p\u003e \u003cp\u003eConsidering the impact of OM on the health and well-being of affected patients, identifying appropriate treatments for the prevention of OM remains a high priority (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Current strategies have somewhat limited efficacy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). For example, palifermin \u0026ndash; a recombinant keratinocyte growth factor that induces epithelial cell proliferation and differentiation \u0026ndash; is recommended for patients undergoing autologous HCT; however, its prevention efficacy for other population groups is uncertain (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The benefits of palifermin also come at a high cost of medication and side effects including taste disturbance (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Photobiomodulation utilizing low-level laser therapy is another strategy that is effective in reducing the incidence of OM in patients undergoing HCT (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Nonetheless, this technology requires expensive equipment and is thus not widely used around the world (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). The most common effective method of preventing OM to date is cryotherapy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This can be administered in two different ways, both of which work via reduction of the blood flow to the mucosal cells (through hypothermia-induced vasoconstriction) leading to low concentrations of the cytotoxic agents in the mouth (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The least expensive and easiest cryotherapy option is using ice chips or ice cubes. These are swished inside of the mouth for around 30 minutes. This method has the advantage of low cost, low toxicity, and simplicity of use (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The tolerability of ice chips is patient dependent as sensitivity to ice and cold varies from individual to individual (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). An alternative option for cryotherapy is an intraoral cooling system, which comes at a higher cost and complexity without proven benefits (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral topical agents were suggested for reducing the likelihood of OM development with uncertain effectiveness, including mucosal protective agents (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), steroids (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), Vitamin E (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), or honey (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Sucralfate (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) and glutamine (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) were not shown to be effective for OM prevention. Benzydamine \u0026ndash; an anti-inflammatory agent (not available in the US) \u0026ndash; is recommended for the prevention of radiotherapy and chemoradiotherapy-induced OM, particularly in patients with head and neck cancer (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), although data regarding chemotherapy-induced OM is lacking. Over-the-counter oral solutions containing a combination of analgesics, anti-inflammatory, and mucosal protective compounds are frequently used and prescribed for protection from mucositis (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), although their clinical efficacy also remains uncertain (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). These recommendations, however, are given for specific patient populations, such as those undergoing autologous hematopoietic stem-cell transplantation or individuals with head and neck cancer undergoing radiotherapy or combined radio-chemotherapy (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOne likely cause of the failure of oral topical medications to significantly impact OM is that the mouth has unique pharmacokinetic properties that limit mucosal exposure to the active ingredients of these medications. Topical medications such as mouthwashes and rinses are generally swished and swallowed or expectorated after 60\u0026ndash;120 seconds. Like topically applied gels, the active ingredients that remain attached to the oral mucosa are responsible for the action of the medication (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). However, the portion of the medication that remains adherent to the mucosal surface after swallowing or expectoration is subject to rapid clearing. This occurs from salivary dilution, mouth movement, and swallowing (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Using a novel testing methodology, our group has demonstrated rapid clearance of a gel from the oral cavity, often within a few minutes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Based on these properties, a device that enhances the oral retention of oral topical medications is hypothesized to improve their efficacy.\u003c/p\u003e \u003cp\u003eBocaliner\u0026trade; is a soft, pliable orally inserted device that is designed to increase the oral resonance time to topical medications. A prior proof of concept study of an oral gel (alginate) showed that Bocaliner increased the concentration and duration of oral retention of alginate mixed with an ETOH marker (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). It is hypothesized that the increased area under the curve of oral concentration versus the time curves of an alginate gel reflects the intrinsic properties of the device. Bocaliner is designed to provide a cover over portions of the oral mucosa, covers the parotid gland and some submandibular gland ostia, and keeps the mouth still during use (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe results of this Phase 1 portion of the SPOM trial showed that the new medical device is tolerated among patients with hematologic malignancies for two weeks since the start of chemotherapy when using it with either benzydamine or saline mouthwash. No specific differences in the outcomes were observed with the concomitant application of either topical medication. The latter implies that the device can be safely used with different local treatment options. Although 29% of participants had some degree of side effects, most of them were self-limited and none of them were serious enough to drop out or stop the cancer treatment. It is yet unknown whether the adjunctive use of the device leads to better outcomes in terms of reduction of OM rates, decrease in grade of and symptomatology related to OM, and shortening of OM duration.\u003c/p\u003e \u003cp\u003eIn conclusion, analysis of the Phase 1 data collected as part of a Phase 1/Phase 2 clinical trial indicates that a new medical device designed to increase the oral dwell time of active ingredients in oral topical medications was well tolerated in a group of patients with hematologic malignancies undergoing systemic chemotherapy. Future research is needed to define optimal strategies for the prevention of chemotherapy-induced OM.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and limitations\u003c/h2\u003e \u003cp\u003eOur study has some important limitations. Several variables (e.g., basic oral care level, dosage and intensity of chemotherapeutic agents, number of previously received treatments, and stage of the disease) were not assessed, which could have potentially influenced the results. The outcomes demonstrating the tolerability and safety of the device were based on questionnaires filled out by patients, which reflected their subjective experience with the device. It was also not possible to examine how compliant and consistent patients were with their preventive treatment for OM. Lastly, this study employed a descriptive analysis, which further limits the interpretation and generalizability of the results.\u003c/p\u003e \u003cp\u003eWe believe that these limitations are balanced by strengths. Our study used patient-reported outcomes implemented in real-world clinical settings, which were not changed or adjusted by the study design. Patients continued to receive their management as usual despite their use of the intervention, and no patient stopped their treatment because of it. Furthermore, physicians managing participants\u0026rsquo; diseases had minimal influence on patients' reports regarding the use of the device.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest\u003c/h2\u003e\n\u003cp\u003e\u003cstrong\u003eEli D. Ehrenpreis MD, AGAF, FACG\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Eli D. Ehrenpreis is the CEO and scientific advisor for E2Bio Life Sciences and is the inventor of Bocaliner\u0026trade;.\u003c/p\u003e\n\u003ch2\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eEli D Ehrenpreis MD is the inventor of Bocaliner and CEO of E2Bio Life Sciences, LLC, the company providing funding for this study.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis study was funded by E2Bio Life Sciences, LLC, the inventors and developers of Bocaliner\u0026trade;.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eAO, LH, AV, YH, MG and EDE were involved in the initial planning and design of the study. AO, YH, and EDE were involved with entering the study on the clinicaltrials.gov database. AO and YH were involved in preparing paperwork for the institutional analysis of the protocol. AO, LH, AV, NM, MB, MG, TO, SM, RP, NG and YH were involved in subject recruitment, study implementation in Armenia, data collection, and clinical follow-up of study subjects. AO and YH performed data analysis and initial manuscript preparation. AO completed the manuscript. All authors reviewed the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors wish to acknowledge the following individuals for their assistance with this study.Hasmik Oseyan, Levon Evoyan, Armine Farmazyan, Amalya Chakhoyan, Hayk Grigoryan, Anahit Ter-Grigoryan, Anna Sevoyan, Avetis Gharibyan, Anahit Aynajyan, Karapet Hakobyan, Martin Nubaryan, Seda Dabaghyan, and Arsene Mekinian. The authors also wish to acknowledge Dr. Joel Epstein for his advice on study design and implementation.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eData provided in this study will be made available to interested researchers.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eColella G, Boschetti CE, Vitagliano R, Colella C, Jiao L, King-Smith N, Li C, Nuoh Lau Y, Lai Z, Mohammed AI, Cirillo N. Interventions for the Prevention of Oral Mucositis in Patients Receiving Cancer Treatment: Evidence from Randomised Controlled Trials. Curr Oncol. 2023 Jan 10;30(1):967-980. doi: 10.3390/curroncol30010074. PMID: 36661723; PMCID: PMC9858113.\u003c/li\u003e\n\u003cli\u003eSonis ST. A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment. Support Care Cancer. 2021 Sep;29(9):4939-4947. doi: 10.1007/s00520-021-06108-w. Epub 2021 Mar 13. PMID: 33712912; PMCID: PMC8295245.\u003c/li\u003e\n\u003cli\u003eKoneru S, Lukas N, Doane M, Pattullo G, MacPherson R. Patient-controlled analgesia and oral mucositis pain in hematological malignancies. J Opioid Manag. 2022 Jul-Aug;18(4):309-316. doi: 10.5055/jom.2022.0726. PMID: 36052929.\u003c/li\u003e\n\u003cli\u003ePulito C, Cristaudo A, Porta C, Zapperi S, Blandino G, Morrone A, Strano S. Oral mucositis: the hidden side of cancer therapy. J Exp Clin Cancer Res. 2020 Oct 7;39(1):210. doi: 10.1186/s13046-020-01715-7. PMID: 33028357; PMCID: PMC7542970.\u003c/li\u003e\n\u003cli\u003eJones JA, Avritscher EB, Cooksley CD, Michelet M, Bekele BN, Elting LS. Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer. Support Care Cancer. 2006 Jun;14(6):505-15. doi: 10.1007/s00520-006-0055-4. Epub 2006 Apr 7.\u003c/li\u003e\n\u003cli\u003eVera-Llonch M, Oster G, Ford CM, Lu J, Sonis S. Oral mucositis and outcomes of allogeneic hematopoietic stem-cell transplantation in patients with hematologic malignancies. Support Care Cancer. 2007 May;15(5):491-6. doi: 10.1007/s00520-006-0176-9. Epub 2006 Dec 1.\u003c/li\u003e\n\u003cli\u003eElad S, Cheng KKF, Lalla RV, Yarom N, Hong C, Logan RM, Bowen J, Gibson R, Saunders DP, Zadik Y, Ariyawardana A, Correa ME, Ranna V, Bossi P; Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2020 Oct 1;126(19):4423-4431. doi: 10.1002/cncr.33100. Epub 2020 Jul 28. Erratum In: Cancer. 2021 Oct 1;127(19):3700.\u003c/li\u003e\n\u003cli\u003eEhrenpreis E, Ehrenpreis A. Development of a soft mucosal lining device to enhance the retention of topical treatments for oral mucositis. Abstracts for MASCC/ISOO Annual Meeting 2019. \u003cem\u003eSupport Care Cancer\u003c/em\u003e \u003cstrong\u003e27\u003c/strong\u003e (Suppl 1), 1\u0026ndash;302 (2019). https://doi.org/10.1007/s00520-019-04813-1\u003c/li\u003e\n\u003cli\u003eLibero Italo Giannola, Flavia Maria Sutera \u0026amp; Viviana De Caro (2013) Physical methods to promote drug delivery on mucosal tissues of the oral cavity, Expert Opinion on Drug Delivery, 10:10, 1449-1462, DOI: 10.1517/17425247.2013.809061\u003c/li\u003e\n\u003cli\u003ePaderni C, Compilato D, Giannola LI, Campisi G. Oral local drug delivery and new perspectives in oral drug formulation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Sep;114(3):e25-34. doi: 10.1016/j.oooo.2012.02.016. Epub 2012 Jul 6. PMID: 22771408.\u003c/li\u003e\n\u003cli\u003eElad S, Yarom N. The Search for an Effective Therapy and Pain Relief for Oral Mucositis. JAMA. 2019 Apr 16;321(15):1459-1461. doi: 10.1001/jama.2019.3269. No abstract available.\u003c/li\u003e\n\u003cli\u003eWilairat P, Kengkla K, Kaewpanan T, Kaewthong J, Ruankon S, Subthaweesin C, Stenehjem DD, Saokaew S. Comparative efficacy and safety of interventions for preventing chemotherapy-induced oral mucositis in adult cancer patients: a systematic review and network meta-analysis. European Journal of Hospital Pharmacy. 2020 Mar 1;27(2):103-10.\u003c/li\u003e\n\u003cli\u003eLogan RM, Al-Azri AR, Bossi P, Stringer AM, Joy JK, Soga Y, Ranna V, Vaddi A, Raber-Durlacher JE, Lalla RV, Cheng KK. Systematic review of growth factors and cytokines for the management of oral mucositis in cancer patients and clinical practice guidelines. Supportive Care in Cancer. 2020 May;28:2485-98.\u003c/li\u003e\n\u003cli\u003eZadik Y, Arany PR, Fregnani ER, Bossi P, Antunes HS, Bensadoun RJ, Gueiros LA, Majorana A, Nair RG, Ranna V, Tissing WJ. Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines. Supportive Care in Cancer. 2019 Oct 1;27:3969-83.\u003c/li\u003e\n\u003cli\u003eAl-Rudayni AH, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of oral cryotherapy in the prevention of oral mucositis associated with cancer chemotherapy: systematic review with meta-analysis and trial sequential analysis. Current Oncology. 2021 Jul 29;28(4):2852-67.\u003c/li\u003e\n\u003cli\u003eAl-Rudayni AH, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of oral cryotherapy in the prevention of oral mucositis associated with cancer chemotherapy: systematic review with meta-analysis and trial sequential analysis. Current Oncology. 2021 Jul 29;28(4):2852-67.\u003c/li\u003e\n\u003cli\u003eWalladbegi J, Smith SA, Grayson AK, Murdoch C, Jontell M, Colley HE. Cooling of the oral mucosa to prevent adverse effects of chemotherapeutic agents: An in vitro study. Journal of Oral Pathology \u0026amp; Medicine. 2018 May;47(5):477-83.\u003c/li\u003e\n\u003cli\u003eJohansson JE, Bratel J, Hardling M, Heikki L, Mellqvist UH, Hasseus B. Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomised, open-label, phase 3, non-inferiority trial. Bone marrow transplantation. 2019 Sep;54(9):1482-8.\u003c/li\u003e\n\u003cli\u003eWalladbegi J, Henriksson R, Tavelin B, Svanberg A, Larfors G, J\u0026auml;dersten M, Schjesvold F, Mahdi A, Garming Legert K, Peterson DE, Jontell M. Efficacy of a novel device for cryoprevention of oral mucositis: a randomized, blinded, multicenter, parallel group, phase 3 trial. Bone Marrow Transplantation. 2022 Feb;57(2):191-7.\u003c/li\u003e\n\u003cli\u003eInnocenti M, Moscatelli G, Lopez S. Efficacy of gelclair in reducing pain in palliative care patients with oral lesions: preliminary findings from an open pilot study. Journal of pain and symptom management. 2002 Nov 1;24(5):456-7.\u003c/li\u003e\n\u003cli\u003eKuo CC, Wang RH, Wang HH, Li CH. Meta-analysis of randomized controlled trials of the efficacy of propolis mouthwash in cancer therapy-induced oral mucositis. Supportive Care in Cancer. 2018 Dec;26:4001-9.\u003c/li\u003e\n\u003cli\u003eRugo HS, Seneviratne L, Beck JT, Glaspy JA, Peguero JA, Pluard TJ, Dhillon N, Hwang LC, Nangia C, Mayer IA, Meiller TF. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. The Lancet Oncology. 2017 May 1;18(5):654-62.\u003c/li\u003e\n\u003cli\u003eYarom N, Hovan A, Bossi P, Ariyawardana A, Jensen SB, Gobbo M, Saca-Hazboun H, Kandwal A, Majorana A, Ottaviani G, Pentenero M. Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines\u0026mdash;part 1: vitamins, minerals, and nutritional supplements. Supportive Care in Cancer. 2019 Oct 1;27:3997-4010.\u003c/li\u003e\n\u003cli\u003eChiara S, Nobile MT, Vincenti M, Gozza A, Pastrone I, Rosso M, Rosso R. Sucralfate in the treatment of chemotherapy-induced stomatitis: a double-blind, placebo-controlled pilot study. Anticancer research. 2001 Sep 1;21(5):3707-10.\u003c/li\u003e\n\u003cli\u003eOkuno SH, Woodhouse CO, Loprinzi CL, Sloan JA, LaVasseur BI, Clemens-Schutjer D, Swan D, Axvig C, Ebbert LP, Tirona MR, Michalak JC. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. American journal of clinical oncology. 1999 Jun 1;22(3):258-61.\u003c/li\u003e\n\u003cli\u003eNicolatou-Galitis O, Bossi P, Orlandi E, Bensadoun RJ. The role of benzydamine in prevention and treatment of chemoradiotherapy-induced mucositis. Supportive Care in Cancer. 2021 Oct;29:5701-9.\u003c/li\u003e\n\u003cli\u003eDaugelaite G, Uzkuraityte K, Jagelaviciene E, Filipauskas A. Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis. Medicina (Kaunas). 2019 Jan 22;55(2):25. doi: 10.3390/medicina55020025.\u003c/li\u003e\n\u003cli\u003eVaroni EM, Molteni A, Sardella A, Carrassi A, Di Candia D, Gigli F, Lodi F, Lodi G. Pharmacokinetics study about topical clobetasol on oral mucosa. J Oral Pathol Med. 2012 Mar;41(3):255-60. doi: 10.1111/j.1600-0714.2011.01087.x. Epub 2011 Sep 22. PMID: 21950548.\u003c/li\u003e\n\u003cli\u003eChan A, Ignoffo RJ. Survey of topical oral solutions for the treatment of chemo-induced oral mucositis. J Oncol Pharm Pract. 2005 Dec;11(4):139-43. doi: 10.1191/1078155205jp166oa. PMID: 16595065.\u003c/li\u003e\n\u003cli\u003eSio TT, Le-Rademacher JG, Leenstra JL, Loprinzi CL, Rine G, Curtis A, Singh AK, Martenson JA Jr, Novotny PJ, Tan AD, Qin R, Ko SJ, Reiter PL, Miller RC. Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial. JAMA. 2019 Apr 16;321(15):1481-1490. doi: 10.1001/jama.2019.3504. PMID: 30990550; PMCID: PMC6484809.\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":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4810150/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4810150/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e. An estimated 40% of patients undergoing systemic chemotherapy develop oral mucositis (OM), a major cause of morbidity in cancer patients. These are only a few options for preventing and treating OM, and these do not include FDA-registered devices. Bocaliner™ is an FDA-registered Class I medical device, designed to enhance the effects of oral topical therapies by prolonging the retention of local agents. This study examines the tolerability of the device in a group of patients with hematologic malignancies undergoing systemic chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e. An initial interim analysis of data from Phase 1/Phase 2 randomized, controlled trial SPOM (Study for the Prevention of Oral Mucositis, NCT05338398) was performed. Patients with blood malignancies undergoing chemotherapy at the Yeolyan Hematology and Oncology Center (Yerevan, Armenia) were randomized into two groups after initiation of chemotherapy: benzydamine (0.15%,120mL) or saline (0.9%, 120mL) mouthwash both applied multiple times daily for 14 days after the start of the systemic treatment. Half of the patients in each study group were randomly assigned to a Bocaliner device with instructions for use immediately following each mouthwash use. Patients completed questionnaires regarding the tolerability and safety of the device on days 1 and day 14 of chemotherapy and use of the device.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e. At the time of the interim analysis, 28 patients who received oral devices had completed the study. The mean age of participants was 49 years and 14 (50%) were female. The median number of times of medical device daily use was 3, and the median duration of each use was 10 minutes. On the initial tryout of the device, 22 (71%) of patients reported tolerating it well, and 6 (29%) reported it caused some discomfort. After 14 days of use, 15 patients (35.7%) reported benefit from the device, with 6 (21.4%) of patients stating the device helped to reduce pain, 4 (14.3%) indicating that it helped them to eat, and 5 (17.8%) patients claiming both benefits. Adverse events after 14 days of use included discomfort (n=2, 7.1%), pain around the cheekbone (n=3, 10.7%), nausea (n=2, 7.1%), and increased salivation (n=1, 3.6%); none of these led to discontinuation of using the device. Eighteen (64%) participants said they would use the device again. Five patients (17.8%) developed OM during chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e. The use of a new medical device designed to enhance oral topical medications in combination with oral topical therapy is well tolerated among patients with hematologic malignancies undergoing systemic chemotherapy. Future studies are planned to evaluate its efficacy for enhancing the prevention and/or treatment of OM with oral topical therapies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinicalTrials.gov ID \u003c/strong\u003eNCT05338398, filed 2022-4-15\u003c/p\u003e","manuscriptTitle":"Tolerability and Safety of a New Oral Device for Enhancing Prevention and Treatment of Oral Mucositis in a Group of Patients with Hematologic Malignancies Undergoing Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-04 23:06:34","doi":"10.21203/rs.3.rs-4810150/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-19T22:53:13+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-19T15:42:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-17T14:05:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"279570671721174349475404240072577404061","date":"2025-01-10T02:38:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192610037381114416824286983010593513025","date":"2025-01-08T14:57:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58369080613697858205081076925279645170","date":"2024-09-13T13:42:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-12T00:12:15+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-10T16:34:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-01T01:20:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2024-07-26T20:45:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"84a91d46-8e27-42f8-a757-1a49a14ee028","owner":[],"postedDate":"September 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-04T16:46:40+00:00","versionOfRecord":{"articleIdentity":"rs-4810150","link":"https://doi.org/10.1007/s00520-025-09722-0","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2025-07-31 16:38:10","publishedOnDateReadable":"July 31st, 2025"},"versionCreatedAt":"2024-09-04 23:06:34","video":"","vorDoi":"10.1007/s00520-025-09722-0","vorDoiUrl":"https://doi.org/10.1007/s00520-025-09722-0","workflowStages":[]},"version":"v1","identity":"rs-4810150","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4810150","identity":"rs-4810150","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}