https://www.researchprotocols.org/issue/feed 2024-12-31T14:00:04-05:00 JMIR Publications editor@jmir.org Open Journal Systems Unless stated otherwise, all articles are open-access distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work ("first published in JMIR Research Protocols...") is properly cited with original URL and bibliographic citation information. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org/, as well as this copyright and license information must be included. JMIR Res Protoc publishes research protocols, current and ongoing trials, and grant proposals in all areas of medicine (with an initial focus on ehealth/mhealth). Publish your work in this journal to let others know what you are working on, to facilitate collaboration and/or recruitment, to avoid duplication of efforts, to create a citable record of a research design idea, and to aid systematic reviewers in compiling evidence. Research protocols or grant proposals that are funded and have undergone peer-review will receive an expedited review if you upload peer-review reports as supplementary files. https://www.researchprotocols.org/2026/1/e91675 2026-07-28T14:45:10-04:00 Leyla Özmen Christian Burisch Daniel Gödde Frank Breuckmann Jan Ehlers Timur Sellmann

Background: Continuing medical education (CME) is a legal and ethical obligation for physicians in Germany. The rapid rise of large language models (LLMs) such as ChatGPT, Gemini, Claude, and Grok raises concerns about the integrity of CME assessments, as LLMs can already pass German CME tests. Objective: This study aims to determine whether the choice of document format (searchable PDF, protected PDF, raster PDF, or vector PDF) and LLM influences the ability of LLMs to solve CME test questions at rates exceeding the passing threshold specified for each CME module (typically 70%). Methods: In a fully crossed within-subjects repeated-measures design, 18 expired CME articles from 3 major German publishers across 6 specialties will be converted into 3 cheating-impeding PDF formats and processed alongside the original PDF files by 4 current LLMs (GPT-5, Claude Sonnet 4, Grok-4, and Gemini 3). This results in 16 model-format combinations. Each model will answer every article 3 times per file-format condition, with outcomes derived from aggregated run-level results. The primary outcome is the proportion of correctly answered questions; the secondary outcome is the pass/fail rate. Results: The study has been approved by the Witten/Herdecke University Ethics Committee (S-260/2025; dated August 10, 2025) and is preregistered at the Open Science Framework. The study is supported by internal departmental resources only, and no external funding was received. Because this protocol evaluates LLMs using expired CME materials, no human participants are being recruited. Data collection is planned to begin in June 2026 and is expected to last approximately 4 weeks. At the time of manuscript submission, no data have been collected or analyzed. Results are expected to be available after the completion of data collection and statistical analysis in 2026. The analyses will quantify performance differences across document formats; these findings may inform the feasibility of nonsearchable document formats as a temporary measure to reduce LLM-enabled cheating risks in CME contexts. Conclusions: By quantifying how document format constrains LLM performance, this study aims to evaluate simple technical safeguards that may reduce artificial intelligence–assisted manipulation of CME tests and inform regulators and CME providers about how to balance assessment validity, accessibility, and responsible LLM integration into postgraduate medical education. Trial Registration: OSF Registries osf.io/v96r5; https://osf.io/v96r5/overview International Registered Report Identifier (IRRID): DERR1-10.2196/91675

2026-07-28T14:45:10-04:00 https://www.researchprotocols.org/2026/1/e90617 2026-07-28T14:45:10-04:00 Chunfeng Xiao Jing Wei Tao Li Jinya Cao Qiaoyan Li Yanping Duan Wenqi Geng Boheng Zhu Bingzhou Liu Yongxue Li

Background: Pharmacotherapy for common mental disorders is frequently limited by adverse events and suboptimal adherence. While music therapy offers a promising nonpharmacological alternative, its clinical utility is currently constrained by limited accessibility, inconsistent efficacy, and a lack of mechanistic clarity. Objective: This study aims to describe the development of individualized (receptive) music therapy (IMT), an artificial intelligence (AI)–enabled, neuroscience-guided intervention, and to evaluate its efficacy, safety, and underlying neurobiological mechanisms in adults with major depressive disorder, generalized anxiety disorder, and primary insomnia. Methods: This multistage research program is being conducted at Peking Union Medical College Hospital and comprises four sequential studies: (1) a cross-sectional pilot study (n=20) to benchmark clinical and electroencephalography features, (2) a prospective cohort study (n=80) evaluating the efficacy and safety of nonindividualized receptive music therapy, (3) a pilot randomized clinical trial (n=300) comparing nonindividualized therapy with IMT over 8 weeks, and (4) a prospective validation study (n=60) of a treatment-response prediction model. Participants include adults aged 18 to 60 years with mild-to-moderate major depressive disorder, generalized anxiety disorder, or primary insomnia, along with healthy controls. In the nonindividualized arm, participants engage in daily 30-minute listening sessions using therapist-curated instrumental tracks designed to regulate mood. In the IMT arm, an AI generation pipeline creates bespoke instrumental tracks based on weekly participant preferences regarding tempo, instrumentation, and emotional valence. To equalize participant–researcher contact across arms and reduce attention and expectation bias, participants in the nonindividualized arm complete a weekly music-experience questionnaire matched in length and timing to the IMT arm’s weekly preference assessment, and treatment credibility and outcome expectancy are measured at baseline in both arms. The primary outcomes are the response rate at 8 weeks (defined as ≥50% reduction in Montgomery-Åsberg Depression Rating Scale [MADRS], Hamilton Anxiety Rating Scale [HAMA], or Pittsburgh Sleep Quality Index [PSQI] scores) and changes in quantitative electroencephalography characteristics. Secondary outcomes include changes in MADRS, HAMA, and PSQI scores from baseline to 8 weeks. Results: Ethical approval was obtained from the Ethics Review Committee of Peking Union Medical College Hospital (I-24PJ0689). Written informed consent will be obtained from all participants. The recruitment started on May 24, 2024, and the study is expected to be completed by December 2027. Results will be disseminated via peer-reviewed publications, conference presentations, and stakeholder communications. Authorship will follow the International Committee of Medical Journal Editors (ICMJE) criteria. The participant-level dataset will be available upon reasonable request. Conclusions: This protocol outlines a translational framework designed to address the “therapeutic ceiling” of traditional music therapy. By integrating generative AI with neurophysiological monitoring, this program aims to develop a scalable, precision-medicine approach to mental health care that is both clinically effective and biologically grounded. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400083246; https://tinyurl.com/mwcsh48z International Registered Report Identifier (IRRID): PRR1-10.2196/90617

2026-07-28T14:45:10-04:00 https://www.researchprotocols.org/2026/1/e93754 2026-07-28T14:30:11-04:00 Amanda Coupe Jessica Pater Rachel Pfafman Victor P Cornet Elisabeth Andrews Mindy Flanagan Dana Albright Abhinay Balasani Christopher Becker Brian Parise Erik Hess Tammy Toscos

Background: Substance use disorder (SUD) represents a significant public health concern in the United States. SUD recovery is complex and individualized, and support provided by peer recovery coaches (PRCs) can improve outcomes. The PRC-client relationship requires bidirectional mediated communication that is often informal but should be trackable, efficient, and aligned with health care privacy and security regulations. Current workflows and available apps do not meet these needs, illustrating the opportunity for client-centered technology tools. We have developed Peer PLUS (People Leveraging Urgent Support; Parkview Health System, Inc), a HIPAA (Health Insurance Portability and Accountability Act)-compliant mobile app and client management system, to address this need; however, the platform has not yet been tested in a clinical setting. Objective: We describe the protocol for the evaluation of our digital health platform to identify its perceived usability, potential sustained use, and potential impact on treatment-related outcomes, as well as to assess its feasibility for a future randomized controlled trial and develop an implementation tool kit to facilitate use by other organizations. Methods: Our evaluation leveraged user-centered design (UCD) and implementation science frameworks (Reach, Effectiveness, Adoption, Implementation, and Maintenance [RE-AIM]). We conducted prelaunch ethnographic observations of 3 PRCs’ workflows for an understanding of user needs. During subsequent in-the-wild testing, PRC-client dyads will use the platform for asynchronous communication within their standard support relationship. We will deploy periodic electronic surveys, including the System Usability Scale (SUS) to assess perceived usability during beta testing, and additional validated measures assessing specific treatment-related outcomes (ie, recovery, quality of care, and therapeutic alliance) during pilot testing. App use log data will be leveraged to assess the likelihood of sustained use. After each test, UCD-focused stakeholder engagements will further elucidate opportunities for platform refinement and implementation tool kit development. Feasibility targets include SUS scores of 68 or more, 25% client eligibility and enrollment rate, and 20% increased contacts between PRCs and enrolled vs nonenrolled clients. Results: This project was funded in March 2023. Beta test recruitment began in January 2024, with 3 tests completed by November 2024 (3 PRCs and 7 clients). Pilot recruitment began in August 2025. Pilot testing and analyses will continue in 2026. If feasibility metrics are met, the platform will be tested in a later study phase that will include a randomized controlled trial and a second pilot trial to test implementation at a different organization. Conclusions: Our evaluation assesses whether Peer PLUS is an efficient and usable tool that meets identified communication and documentation needs of clients and PRCs while fostering increased connection, which could suggest the likelihood of sustained use and improved treatment outcomes. This project contributes to the UCD and implementation science fields by demonstrating the importance of merging these frameworks during the design and evaluation of novel digital health solutions. International Registered Report Identifier (IRRID): DERR1-10.2196/93754

2026-07-28T14:30:11-04:00 https://www.researchprotocols.org/2026/1/e83416 2026-07-28T13:15:08-04:00 Emma Jenkinson Rona Moss-Morris Natasha Seaton Eli Silber David Okai Abigail Wroe Simon Brodie Sam Norton Joanna L Hudson

Background: Comorbid anxiety and depression in patients with multiple sclerosis (MS) are common, conferring a greater risk of poorer outcomes and increased health care costs. Few MS services include scalable treatment pathways for psychological distress. Objective: This study aims to conduct a real-world longitudinal study evaluating the implementation and potential effectiveness of an integrated pathway involving digital screening for psychological distress and COMPASS-MS, a therapist-guided digital cognitive behavioral therapy tailored to the challenges of living with MS. Methods: This is a mixed methods, observational, real-world, longitudinal study being conducted in the United Kingdom. Routine mental health screening in the MS clinic will identify patients experiencing distress (using predefined clinical cutoffs), who will be assessed for eligibility for psychological treatment, including the COMPASS-MS program. Participants will receive COMPASS-MS online over approximately 12 weeks (including up to six 30-min therapist sessions). The implementation, reach, and adoption of the treatment pathway within a specialist MS service will be assessed using aggregate data on the uptake of mental health screening, eligibility, and consent rates for COMPASS-MS, as well as the number of COMPASS-MS sessions completed. Interviews with patients and health care professionals will primarily assess the scalability and potential or actual barriers and facilitators of the new pathway. Potential effectiveness will be assessed using participant questionnaires at preintervention and 12 weeks postintervention. The primary effectiveness outcome will be pre-post changes in distress (Patient Health Questionnaire Anxiety and Depression Scale scores). Quantitative data will be summarized using descriptive statistics and mixed effects models. Qualitative data will be analyzed using reflexive thematic and framework analysis. Results: Recruitment of both patients and health care professionals began in June 2024. For patients, recruitment was completed as of September 2025, including 82 participants. For health care professionals and stakeholders, as of September 2025, 7 had consented and completed interviews, and 13 more were expected to be recruited by August 2026. Data analysis has not yet started; however, quantitative results are expected by September 2026. Conclusions: The study findings will inform treatment pathways that can be incorporated into MS clinics and highlight adaptations or implementation protocols required to increase future scalability and effectiveness. Trial Registration: ClinicalTrials.gov NCT06222359; https://clinicaltrials.gov/study/NCT06222359 International Registered Report Identifier (IRRID): DERR1-10.2196/83416

2026-07-28T13:15:08-04:00 https://www.researchprotocols.org/2026/1/e86608 2026-07-28T13:00:21-04:00 Apolline Blazer Sabrina Rouat Laure Guittard Pauline Drouin Julien Péron Béatrice Fervers Julien Carretier Guillaume Broc Laurent Letrilliart Jean-Baptiste Fassier Marion Lamort-Bouché

Background: Women with breast cancer face many barriers to returning to work (RTW) after their treatment. The Facilitating and Sustaining the Return to Work After Breast Cancer (FASTRACS) intervention aims to facilitate and sustain functional RTW. Objective: The main objective of the RECOVA-FASTRACS (Realist Collaborative Evaluation of a Work Disability Prevention Program for Breast Cancer Survivors) study is to evaluate the processes using a realist approach that analyzes what works, how, for whom, and under what circumstances. Methods: The RECOVA-FASTRACS study uses a mixed methods design to assess the implementation, context, and impact mechanisms of the FASTRACS intervention. The qualitative analysis will include 2 main components: a trajectory analysis and a focus group assessment. The trajectory analysis will examine the experiences of women who participated in the intervention and key individuals involved in their RTW process. We will use semistructured interviews according to the multiple-case study method. Additionally, to explore organizational and professional practices, focus groups will be conducted with professionals who deliver the intervention. To analyze the trajectories, embedded and iterative integration will combine the qualitative findings with relevant quantitative data from the FASTRACS randomized controlled trial for 5 domains: personal situation, professional situation, RTW, care pathway, intervention tool use, and perceived usefulness. Results: The RECOVA-FASTRACS study received funding in 2022. Recruitment and qualitative data collection began in month 6. Final analyses are expected to be completed by the end of 2026, with dissemination of the main findings anticipated in late 2027. Conclusions: Our mixed methods realist evaluation will provide a detailed analysis of the intervention processes, helping to identify impact mechanisms within specific contexts. This approach is meant to ensure a more informed and realist deployment of the intervention by professionals following the study. Trial Registration: ClinicalTrials.gov NCT05919498; https://clinicaltrials.gov/study/NCT05919498 International Registered Report Identifier (IRRID): DERR1-10.2196/86608

2026-07-28T13:00:21-04:00 https://www.researchprotocols.org/2026/1/e64658 2026-07-27T11:45:12-04:00 Rania Hammami Emna Derbel Wafa Elleuch Rahma Kallel Aimen Dammak Faiza Safi Fatma Mhiri Hichem Denguir Mootez Billah Oueslati Souad Ferjani Milouchi Sami Milouchi Faten Dhouib Naziha Turki

Background: Simulation-based training has demonstrated effectiveness in enhancing proficiency in interventional procedures. The endovascular treatment of peripheral arterial lesions has become a prominent minimally invasive therapeutic option. However, operators from various specialties, including Interventional Cardiology, Interventional Radiology, and Vascular Surgery, often follow diverging guideline recommendations and training pathways. Despite growing use of simulation in this field, the influence of an operator’s specialty on learning outcomes remains poorly understood. Objective: This study aimed to evaluate the impact of simulation training on peripheral angioplasty performance scores across different interventional specialties and assess how specialty-specific factors influence skill acquisition. Methods: This quasi-experimental observational study will be conducted at the Simulation Center of the Faculty of Medicine of Sfax, Tunisia (trial registration: PACTR Trial ID 30697). Participants consist of 60 novice fellows from three specialties: Cardiology (n=20), Interventional Radiology (n=20), and Vascular Surgery (n=20). All participants will undergo identical simulation training using a high-fidelity Mentice simulator, comprising five standardized clinical scenarios addressing peripheral angioplasty of complex iliac and femoral lesions (TASC B-D). Each participant will receive a 4-hour hands-on training session with pre- and posttest assessments using a 25-item Global Score (10 knowledge items, 15 competence items). Primary outcomes consist of percentage change in performance scores from baseline to posttraining (threshold for clinical significance:≥25% improvement) and comparison across specialty groups using nonparametric statistics. Secondary outcomes consist of radiation protection parameters, including fluoroscopy duration, cumulative radiation dose, air kerma, and dose area product (KAP), measured by a simulator with real-time ALARA (As Low As Reasonably Achievable) feedback. Results: Study enrollment started on September 15, 2024. As of December 2025, 42 fellows were screened, and 21 have been enrolled (15 Cardiology, 3 Radiology, 3 Vascular Surgery), representing 35% of the target sample (21/60). All 21 enrolled participants completed the full simulation training protocol, with radiation protection parameters recorded for all sessions. Enrollment and data collection are expected to be completed by June 2026, with full results anticipated for publication thereafter. Conclusions: This protocol describes the first comparative study evaluating the impact of high-fidelity simulation on peripheral angioplasty performance across three distinct specialties. Findings are anticipated to provide novel evidence regarding specialty-specific learning trajectories and may inform the development of standardized, specialty-tailored training pathways for complex peripheral interventions. International Registered Report Identifier (IRRID): PRR1-10.2196/64658

2026-07-27T11:45:12-04:00 https://www.researchprotocols.org/2026/1/e93439 2026-07-24T16:00:03-04:00 Hanna Rahimi Anja Poulsen Jette Led Sørensen Ida Madeline Hoffmann Amalie Middelboe Sohlin Line Klingen Gjærde Stine Lund

Background: High-quality neonatal resuscitation (NR) depends on timely execution of technical and nontechnical skills. Simulation-based training improves NR performance, but it is resource-intensive and difficult to deliver at sufficient frequency. Immersive virtual reality (VR) simulation may provide a scalable supplement to traditional mannequin-based training; however, evidence from European neonatal training settings is limited. Objective: The aim of this study is to evaluate whether immersive VR-based simulation training used as a supplement to traditional mannequin-based simulation training improves NR performance among doctors and nurses in Denmark. Methods: NEONATAL is a multicenter, individually randomized, 2-arm controlled superiority trial with a parallel-group pretest-posttest design (trial registration number ISRCTN 43822066). Resident doctors and neonatal nurses from 4 hospitals in Eastern Denmark will be randomized to either traditional mannequin-based NR training alone or traditional mannequin-based simulation training supplemented with immersive VR simulation training. Outcomes will be assessed at baseline and endline at 6 to 8 weeks using standardized neonatal simulation scenarios, validated assessment tools, and questionnaires. Results: The study was funded in July and October 2025, as well as in January 2026. Participant recruitment began in October 2025 and was completed in December 2025, with 66 participants enrolled. Data collection was completed in February 2026. Data cleaning and analysis will take place from March to July 2026, and the results are expected to be published in autumn 2026. This study will provide data on the effectiveness, feasibility, and usability of immersive VR simulation training as a supplement to traditional mannequin-based NR training in routine clinical education. Conclusions: The NEONATAL study addresses an important gap in NR education by evaluating immersive VR simulation training as a supplement to traditional mannequin-based training. Trial Registration: ISRCTN Registry ISRCTN43822066; https://www.isrctn.com/ISRCTN43822066 International Registered Report Identifier (IRRID): DERR1-10.2196/93439

2026-07-24T16:00:03-04:00 https://www.researchprotocols.org/2026/1/e86667 2026-07-24T15:30:15-04:00 Jonathan W Leigh Susan J Pressler Ben S Gerber Mayank Kansal Mia Cajita Spyros Kitsiou

Background: Heart failure (HF) is a major public health problem associated with frequent hospitalizations, high mortality, and substantial health care costs. Self-care is fundamental to improving health outcomes; yet, self-care is commonly poor among patients with HF. SMS text messaging interventions may provide a simple, scalable, and accessible strategy to support HF self-care, particularly among older adults who may face barriers to using more complex digital health technologies. However, the efficacy of text messaging as a standalone intervention for patients with HF remains underexplored. Objective: This protocol paper describes the rationale and design of a pilot randomized controlled trial examining the feasibility, acceptability, and preliminary efficacy of an individually Tailored Text Messaging Intervention to Improve Self-Care in Adults with HF (Text4HF). Methods: This study is a single-site, stage I, parallel-group randomized controlled trial. Participants (n=30) are community-dwelling adults aged 50 years or older with stage C HF and suboptimal self-care, defined as a score of 3 or less on at least 2 items of the Self-Care of Heart Failure Index (SCHFI v7.2). Participants are randomized (1:1) to either a 12-week tailored text messaging intervention (Text4HF) plus usual care or usual care alone. Text messages are triggered based on patient responses to validated instruments assessing evidence-based, modifiable behavioral factors of HF self-care. Feasibility (recruitment and retention) and acceptability of the intervention are assessed as key process outcomes. The main exploratory patient-reported outcome is HF self-care (SCHFI v7.2). Other patient-reported outcomes include medication adherence, adherence to a heart-healthy diet, HF knowledge, health-related quality of life, self-efficacy, and health beliefs. Results: This study was funded in June 2022, and participant recruitment began in September 2024. A total of 26 participants have been enrolled and randomized to the intervention (n=13) and control (n=13) groups. Participants have a mean age of 60 (SD 6.6) years, 46% (12/26) are female, and 73% (19/26) identify as non-Hispanic Black. Half of the participants are individuals with reduced ejection fraction. Study completion is anticipated in June 2026. Conclusions: This protocol describes an important step toward evaluating a scalable, low-cost text messaging intervention designed to improve self-care in patients with HF. Study findings will provide critical data on feasibility and acceptability to guide a future fully powered efficacy trial of Text4HF. Trial Registration: Clinicaltrials.gov NCT06473532; https://clinicaltrials.gov/study/NCT06473532 International Registered Report Identifier (IRRID): DERR1-10.2196/86667

2026-07-24T15:30:15-04:00 https://www.researchprotocols.org/2026/1/e84625 2026-07-23T18:00:20-04:00 Lisa A Niemann Lauren R Violette Andy Cornelius-Hudson Maggie Murphy Carl Capili Mindy Dai Anjuli Wagner Sarah Frey Shireesha Dhanireddy Shaneil E Taylor Karen W Hoover Joanne D Stekler

Background: With shorter window periods than serologic point-of-care (POC) tests and faster turnaround than laboratory-based nucleic acid tests (NAT), POC NATs could improve early detection of HIV. Furthermore, semiquantitative POC NAT may provide real-time monitoring for persons with HIV. There have been limited evaluations of POC NAT implementation in the United States. Objective: This paper describes the protocols and procedures used to evaluate the acceptability and feasibility of POC NAT implementation and test performance in clinical and community settings in Seattle, Washington. Methods: The Greater Access and Impact through POC NAT (GAIN) study was a Centers for Disease Control and Prevention–funded study that enrolled participants at a Ryan White–funded, hospital-based clinic (Madison Clinic) and a community site (Seattle’s LGBTQ+ Center [the Center]). Persons seeking HIV testing, nonoccupational postexposure prophylaxis, or pre-exposure prophylaxis (PrEP) enrolled at either site received the standard of care plus the SAMBA II HIV-1 Qualitative Whole Blood Test (SAMBA Qual) and pooled laboratory HIV NAT, and persons with HIV enrolled at the Center received standard-of-care sexually transmitted infection testing plus the SAMBA II HIV-1 Semiquantitative Whole Blood Test (SAMBA Semi-Q) and laboratory viral load testing. Persons with HIV from Madison Clinic were recruited into a randomized clinical trial (RCT) to compare the clinical standard of care with the addition of the SAMBA Semi-Q (backed up by Food and Drug Administration–approved laboratory NAT). All participants completed a demographic survey during their study visit and contributed prospective data via electronic medical records. Subsets of participants from each group were invited to complete a postvisit acceptability survey and participate in an individual interview. Patient flow was observed at Madison Clinic to assess the impact of POC testing on clinic visit timing. Results: From January 2022 to December 2024, 733 participants completed 753 GAIN research visits. Of those, 491 visits were completed by 489 participants seeking HIV testing and/or PrEP at the Center, and 61 visits were completed by 43 participants seeking HIV testing, nonoccupational postexposure prophylaxis, and/or PrEP at Madison Clinic. Test result data will assess test performance, with analyses anticipated in 2027. Seven people with HIV were enrolled at the Center, and 194 people with HIV were enrolled in the Madison Clinic RCT. Data from patients with HIV at Madison Clinic will be used to conduct a survival analysis evaluating the impact of POC NAT on time to viral suppression and to assess test performance, with analyses anticipated in 2026. In-depth acceptability surveys were completed by 193 participants, and 41 interviews were conducted. These data will contribute to qualitative and mixed methods analyses, which are anticipated in 2026. Time-and-motion observations conducted in 2021 and 2023 included 47 patients; results are anticipated in 2026. Conclusions: The GAIN study is an important evaluation of POC NAT implementation in the United States in community and clinical care settings for HIV diagnosis and viral load monitoring. Results will be reported in future publications. Trial Registration: ClinicalTrials.gov NCT04880200; https://clinicaltrials.gov/study/NCT04880200 International Registered Report Identifier (IRRID): DERR1-10.2196/84625

2026-07-23T18:00:20-04:00 https://www.researchprotocols.org/2026/1/e86281 2026-07-23T18:00:20-04:00 Katrina M Oselinsky Emily B Hill Danielle M Ostendorf Zhaoxing Pan Kristen Bing Liza T Wayland Chloe Simpson Kevin C Clark Anaeli Sandoval Elizabeth A Thomas Ryan J Marker Peter Kabos Paul S MacLean Victoria A Catenacci

Background: Mounting evidence underscores the adverse effects of excess body weight during cancer survivorship, yet many breast cancer survivors struggle to maintain a healthy weight (approximately 70% have overweight or obesity [OW/OB]). Daily caloric restriction with increased physical activity is the standard behavioral weight loss approach; however, many fail to achieve clinically meaningful (>5%) weight loss, emphasizing the need for innovative interventions. A recent investigation found that a behavioral weight loss program focusing on 4:3 intermittent fasting (4:3 IMF) produced 60% greater weight loss among healthy adults with OW/OB with no history of cancer than a program focused on daily caloric restriction. Given these promising results and the need for innovative weight loss strategies among breast cancer survivors, studies testing 4:3 IMF among breast cancer survivors are warranted. Objective: This investigation aimed to evaluate the feasibility, acceptability, and safety of a 4:3 IMF behavioral weight loss program tailored to breast cancer survivors, and to examine exploratory clinical outcomes (eg, body weight, diet adherence, and physical activity) in relation to prespecified thresholds that will inform whether adjustments to the program are needed prior to progression to a larger trial. Methods: In this proof-of-concept feasibility study, individuals with stage I-III breast cancer who have OW/OB and are post–primary therapy will enroll in a 6-month behavioral weight-loss intervention using a 4:3 IMF dietary strategy. Participants will complete a modified fast of approximately 500 kcal per day on 3 non–consecutive days per week, with ad libitum intake the other 4 days per week. Participants will receive virtual, group-based education from a registered dietitian nutritionist that includes a focus on cancer-specific nutrition guidelines. They will also receive in-person, individualized exercise support from an established exercise oncology program to target cancer-specific exercise guidelines. Intervention feasibility will be assessed via participant recruitment, retention, and education class attendance. Acceptability of Intervention Measure, Intervention Appropriateness Measure, Net Promoter Scores, and focus group interviews will be used to assess program acceptability. Proof-of-concept will be evaluated based on whether prespecified thresholds for changes in exploratory clinical outcomes are met. This information will be used to inform progression to a larger trial. Results: This study was funded in January 2022. Data collection began in May 2024 and is ongoing as of April 2026. Recruitment was completed in September 2025 with 31 participants. Study volunteers are currently participating in the 6-month intervention, with data collection anticipated to be completed by Summer 2026, data analysis to begin in Summer/Fall 2026, and initial study results expected by early 2027. Conclusions: This study aimed to examine feasibility, acceptability, and safety of a 4:3 IMF intervention among breast cancer survivors. Data from this study will be used to refine the 4:3 IMF intervention for delivery in a future randomized efficacy trial. Trial Registration: ClinicalTrials.gov NCT06399276; https://www.clinicaltrials.gov/study/NCT06399276 International Registered Report Identifier (IRRID): DERR1-10.2196/86281

2026-07-23T18:00:20-04:00