JMIR Research Protocols

Enhancing Mental Wellness in Kenyan Adolescents and Young People: Protocol for a Platform Development and Usability Study

2026-10-15T16:30:22-04:00

Background: Mental health disorders are a leading cause of disability among adolescents and young people in Kenya, yet access to appropriate and timely support remains severely limited due to shortages of trained professionals, stigma, financial barriers, and geographical inequities. Digital mental health interventions, particularly those leveraging AI, present a promising opportunity to expand access to culturally relevant, low-stigma mental wellness support in low- and middle-income country (LMIC) settings. However, evidence on the feasibility, usability, and acceptability of AI-powered mental health tools for young people in sub-Saharan Africa remains limited. Objective: This study aims to co-design, develop, and evaluate “Dəˈskəs,” a social media–based digital platform featuring an AI-powered chatbot, to support mental wellness among adolescents and young people in Kenya. The primary objectives are to assess the feasibility of implementation, usability and user experience, acceptability, and the platform’s preliminary applicability across diverse urban, peri-urban, and rural contexts. Methods: The study uses a human-centered design (HCD) methodology, conducted in 3 phases: formative research and co-design, platform development and iterative refinement, and implementation with monitoring and evaluation. Adolescents and young people aged 18 to 24 years will be purposively recruited from Kibra (urban), Kikuyu Town (peri-urban), and Nachu (rural). Formative data will be collected through focus group discussions to inform platform design, content, and functionality. During implementation, participants will use the platform for 2 months. Quantitative data will include baseline behavioral health screening using the Global Appraisal of Individual Needs–Short Screener (GAIN-SS) and platform use analytics. Qualitative data will be collected through interviews and feedback sessions to assess usability, user experience, acceptability, and perceived value. Data will be analyzed using descriptive statistics and thematic qualitative analysis. Results: Field activities for the project started in January 2026. Formative data collection was planned to be completed across the 3 Kenyan study sites by the end of February 2026. Usability and user experience testing was planned to run from March 2026 to June 2026. Findings from the formative work, baseline data, and usability and user experience testing will be reported in subsequent original research publications. The study was funded by the Royal Academy of Engineering, UK in 03/2025 and approved by the Strathmore University Institutional Scientific Ethics Review Committee (SU-ISERC; SU-ISERC 2980/25) approved from November 4, 2026. Conclusions: This protocol describes an adolescent-centered, ethically grounded approach to developing and evaluating an AI-enabled digital mental health intervention in an LMIC context. The findings are expected to contribute to the evidence base on the responsible design and implementation of AI-powered mental health tools for adolescents and young people and to inform future scale-up of accessible, culturally relevant digital mental wellness interventions in Kenya and similar settings. International Registered Report Identifier (IRRID): DERR1-10.2196/92983

Socially Embedded Digital Coaching Platform to Promote Healthy Lifestyle and Mental Health in Underprivileged (Pre)Pregnant Couples and Young Families (Our Smart Family Buddy Program): Protocol for a Mixed Methods Study

2026-10-15T16:30:22-04:00

Background: The early life course, that is, from preconception up until the first 1000 days of life, is pivotal for optimizing parental and child health. In deprived settings, unfavorable lifestyle behaviors and poor mental health are more prevalent, while access to effective, context-sensitive support is limited. Digital interventions combined with community-based approaches may help address these disparities. Objective: This protocol describes the methodology and initial progress of the Our Smart Family Buddy (OSFB) program, which aims to develop, implement, and evaluate a socially embedded digital coaching platform to improve nutrition and mental well-being among (pre)pregnant couples and families in deprived neighborhoods. Methods: The OSFB program is a multiphase mixed methods program conducted within a transdisciplinary consortium consisting of 6 interrelated work packages. The program is structured in 3 phases: phase 1, exploration and preparation; phase 2, cocreation, design, and development; and phase 3, prototype evaluation and optimization. Data collection includes quantitative questionnaires, qualitative interviews and focus groups, and digital user data from the platform. The primary outcomes include lifestyle behaviors (nutrition and sleep), mental well-being, user engagement, and implementation outcomes, including feasibility, acceptability, and reach. Results: The program was funded in 2022. A transdisciplinary consortium was established in 2023. Data collection and analysis for phase 1 were conducted between 2023 and 2025, including literature reviews and exploratory interviews. A deprived neighborhood in the municipality of Rotterdam, the Netherlands, was selected as the target neighborhood. The target population was defined as (pre)pregnant couples and families with a child aged <4 years. Phase 2 is ongoing (2024‐2026), focusing on iterative design through locally established field labs and community building. Phase 3 is planned for 2026 to 2028. Conclusions: This protocol describes a socially embedded, multiphase approach to developing and implementing a digital coaching intervention for families in vulnerable circumstances. Through a transdisciplinary approach within a real-world, local community setting, the OSFB program aims to develop a context-sensitive intervention to support sustainable behavior change in early life. International Registered Report Identifier (IRRID): DERR1-10.2196/88913

Efficacy, Effectiveness, and Immunogenicity of the Respiratory Syncytial Virus Prefusion F Vaccine Administered During Pregnancy: Protocol for a Living Systematic Review and Meta-Analysis

2026-10-15T16:15:18-04:00

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease in infants, with the highest burden in the first 6 months of life. Maternal immunization with the bivalent (RSV-A and RSV-B) prefusion F (RSVPreF) protein subunit vaccine (ABRYSVO) is a recently recommended strategy for preventing RSV-related outcomes in infants. First licensed for use in pregnancy in 2023, the RSVPreF vaccine demonstrated efficacy in a single pivotal randomized trial (Maternal Immunization Study for Safety and Efficacy; MATISSE); postlicensure real-world evidence on vaccine effectiveness across settings, seasons, and subgroups and on antibody durability and transplacental transfer remains limited and has not been synthesized in a continuously updated framework, motivating this review. Objective: This living systematic review and meta-analysis will synthesize emerging postlicensure data on the efficacy, effectiveness, and immunogenicity of the RSVPreF vaccine in real-world settings. Methods: We will conduct, in real time, a living systematic review and meta-analysis following Cochrane methods and PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidance, including randomized clinical trials and postlicensure real-world studies (eg, cohort, case-control, test-negative, and quasi-experimental studies). Primary objectives are evaluation of vaccine efficacy and effectiveness in preventing RSV-specific and all-cause respiratory disease and immunogenicity in infants and pregnant individuals. Vaccine effectiveness outcomes include RSV laboratory-confirmed infection, RSV acute respiratory illness, RSV lower respiratory tract disease, RSV hospitalization, RSV complications, all-cause lower respiratory tract disease and hospitalization, and antibiotic use in infants with RSV infection. Immunogenicity outcomes include maternal neutralizing antibody titers, maternal-infant transfer ratios, infant titers over time, and RSV viral load. We will search MEDLINE, Embase, the Cochrane Library, LILACS, Science Citation Index Expanded, Chinese biomedical and citation databases, clinical trial registries from January 2023 onward with no language restrictions, updating at least monthly. Two investigators will independently select studies, extract data, and assess risk of bias. Adjusted estimates will be standardized to vaccine efficacy and effectiveness. Certainty will be graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: This living systematic review was funded in June 2025. Searches began in January 2023 and will continue with surveillance updates at least monthly until April 2028. As of January 2026, 837 records were screened, 105 (12.5%) were assessed in full text, and 12 (1.4%) met the inclusion criteria, of which 10 (1.2%) contributed extractable data. Data collection and analysis are ongoing and displayed on an interactive dashboard. Findings will be disseminated through peer-reviewed publications, conferences, and a real-time dashboard, with the first effectiveness estimates available in July 2026. Conclusions: This living systematic review and meta-analysis will provide a continuously updated synthesis of real-world evidence on maternal RSVPreF vaccination to inform clinical and policy decisions. Trial Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251077829 International Registered Report Identifier (IRRID): DERR1-10.2196/94382

Rapid Innovation of Precision Psychiatry Interventions Using Dynamical Systems Modeling and Ecological Quasi-Experiments: Protocol for a Proof-of-Concept Study on Eating Disorders

2026-10-15T16:15:18-04:00

Background: Nearly 83 million Americans experience mental illness, but fewer than 50% accessed past-year mental health services. Disseminable, potent mental health interventions are critically needed. Standalone digital interventions offer promise for improving clinical outcomes, but the efficacy of these interventions to date is modest, likely due in part to insufficient personalization to patient heterogeneity, varying context, and the stochastic nature of mental health symptoms. Objective: This study seeks to improve the efficacy of precision digital health interventions by developing real-world, person-specific models for psychopathology using ecological data and dynamical systems modeling. Dynamical systems modeling of ecological momentary assessment (EMA) and smartphone sensor data will provide insight into each individual’s maintenance system for psychopathology in their daily life. Just-in-time adaptive interventions (JITAIs) provide support in the moment at specific decision points, often via smartphone, when the risk for maladaptive behaviors is determined to be elevated. This study will use microrandomized assignment to deliver JITAIs at times of risk for maladaptive behavior based on the individual’s dynamical system to evaluate the granular effects and mechanisms of specific therapeutic skills. Proof-of-concept of these methods for improving potency of precision psychiatry digital interventions will be evaluated in eating disorders (EDs), as EDs are characterized by easily measurable maladaptive behaviors, maintained by a complex intersection of biopsychosocial factors, and their frontline treatment, enhanced cognitive behavioral therapy (CBT-E), is primarily behavioral. The aims are to (1) test the hypothesis that person-centered dynamical models will describe risk for dietary restriction, binge eating, and compensatory behaviors with ≥60% average area under the curve; (2) test hypothesized effects and mechanisms of CBT-E skills using JITAIs; and (3) characterize feasibility and acceptability of the standalone JITAI system. Methods: The study will enroll 170 adults with EDs. EMA and smartphone sensor data measuring CBT-E risk factors will be collected for 16 weeks. Participants will receive JITAIs delivered based on their idiographic risk models for 10 weeks. ED symptoms, feasibility, and acceptability data will be collected at the end of the study. The study was registered on ClinicalTrials.gov on May 19, 2026. The first participant was enrolled on July 8, 2026. Results: This project is funded from August 2025 to July 2030. Recruitment will occur from June 29, 2026, to July 2029. Data collection started in July 2026 and will end in November 2029. A total of 4 participants have been enrolled (as of August 14, 2026). Results will demonstrate the efficacy of idiographic dynamical systems modeling for accurately describing real-time behavioral risk and provide insight into the relative effects and mechanisms of key CBT-E skills under conditions of daily life. Conclusions: The study will set the stage for a future randomized controlled trial to evaluate the optimized, standalone JITAI, which will have the potential to substantially improve access to evidence-based mental health care. Trial Registration: ClinicalTrials.gov NCT07600671; https://clinicaltrials.gov/study/NCT07600671 International Registered Report Identifier (IRRID): DERR1-10.2196/104849

Pharmacist-Led Continuous Glucose Monitoring for Prediabetes: Protocol for a Prospective Cohort Study

2026-10-15T16:00:02-04:00

Background: Prediabetes represents a critical intervention window to reduce progression to type 2 diabetes. The current standard of care for treatment of prediabetes is weight loss and lifestyle modification, which are both highly effective, although limited by real-world adherence. It is well recognized that continuous glucose monitoring (CGM) improves glycemic and behavioral outcomes in people with diabetes, although outcomes among people with prediabetes are not well described. Objective: The aim of this study is to evaluate the impact of pharmacist-led CGM on glycemic control and health-related behaviors in adults with prediabetes. Methods: This study includes a prospective pharmacist-led CGM cohort and a matched retrospective usual-care cohort. Adults aged 18 to 70 years with prediabetes (hemoglobin A_1c [HbA_1c] 5.7%-6.4%) will be eligible for the prospective cohort if they have a compatible smartphone and no CGM use in the prior 6 months. Participants will receive CGM (Stelo glucose biosensor; Dexcom) and diabetes self-management education and support over 12 weeks. The primary outcome is the change in HbA_1c at 12 weeks, compared between groups. Secondary outcomes include CGM-derived metrics, changes in Summary of Diabetes Self-Care Activities scores and 36-Item Short Form Health Survey scores, and CGM-related adverse effects. Results: This study was funded in 2026. Recruitment is ongoing, and no participants had been enrolled at the time of writing. The planned sample size is 40 participants: 20 prospective CGM participants and 20 retrospective controls. Outcome data are not yet available. The study is expected to be completed in July 2027, and the results are anticipated to be disseminated in December 2027. Conclusions: This study seeks to evaluate the glycemic impact, behavior change, and safety of pharmacist-led CGM for prediabetes in primary care. Trial Registration: ClinicalTrials.gov NCT07529366; https://tinyurl.com/33bv7u8c

Feasibility of High-Intensity Interval Exercise in Young Adult Survivors of Pediatric Brain Tumor and Young Adults With Isocitrate Dehydrogenase–Mutant Gliomas (HYPE): Protocol for a Randomized Controlled Trial

2026-10-15T13:15:19-04:00

Background: Young adult survivors of pediatric brain tumors and young adult patients with isocitrate dehydrogenase (IDH) mutant gliomas are at risk for cognitive impairment, reduced physical fitness and function, as well as poor health-related quality of life (HRQOL) and psychosocial health. Exercise improves these outcomes; however, both populations remain understudied with respect to exercise interventions. High-intensity interval training (HIIT) is a promising intervention, as it is time-efficient, safe, tolerable, enhances cognition in healthy young adults, and improves physical fitness and quality of life in adult patients and survivors with cancer. However, the feasibility of HIIT is not yet understood in survivors of pediatric brain tumors and patients with IDH-mutant glioma. Objective: The HYPE study is a pilot randomized controlled trial that aims to (1) determine the feasibility of a HIIT exercise intervention for young adult survivors of pediatric brain tumors and patients with IDH-mutant glioma, (2) determine the preliminary efficacy of HIIT to improve physical fitness and function, cognition, HRQOL, and psychosocial health, and (3) explore exercise sustainability and the impact of social determinants of health on study outcomes. Methods: A total of 30 young adult survivors of pediatric brain tumors and patients with IDH-mutant glioma (18‐45 years of age) will be randomized to an exercise or control group. The exercise group performs virtually supervised HIIT 3 times per week for 16 weeks, followed by 16 weeks of self-directed exercise. Exercise involves indoor cycling, and sessions include 20 minutes of high- and low-intensity intervals (high intensity=60-s 60%‐90% peak power output; low intensity=60-s 10% peak power output), and a 5-minute warm-up and cool-down. The control group performs a 16-week stretching program. Feasibility of the HIIT intervention is measured by the number of exercise sessions completed, including total minutes and intensity, and barriers to exercise adherence. Cognition, physical fitness and function, HRQOL, and psychosocial health are measured using standardized assessments and self-report questionnaires. Exercise sustainability is measured by change in study outcomes following the self-directed follow-up period, and social determinants of health are assessed using a self-report questionnaire. Results: Baseline data collection began in February 2024, and 13 participants have been enrolled as of June 2026. The projected study end date is December 2026. Data analysis is planned to begin in January 2027, and findings will be published in the fall of 2028. Conclusions: To our knowledge, this study is the first to use a virtually supervised HIIT intervention in young adult patients and survivors of brain tumor. The findings will elucidate the feasibility of HIIT to design and power a randomized controlled trial to address cancer- and treatment-related sequelae. They will also provide insights into the sustainability of HIIT and the impact of social determinants of health. Trial Registration: ClinicalTrials.gov NCT05740839; https://www.clinicaltrials.gov/study/NCT05740839 International Registered Report Identifier (IRRID): DERR1-10.2196/88718

Effectiveness of Generative AI–Enabled Teaching for Clinical Reasoning in Health Care Education: Protocol for a Systematic Review and Meta-Analysis

2026-10-15T12:30:36-04:00

Background: Clinical reasoning skills are key competencies required by health care professionals. Generative AI (GenAI)–enabled teaching may be able to offer personalized learning; however, its effectiveness compared with traditional teaching methods for developing clinical reasoning capabilities remains underexplored. Objective: This systematic review and meta-analysis will evaluate, synthesize, and compare the evidence on effectiveness in clinical reasoning capabilities between GenAI-enabled teaching and traditional teaching methods in health care education. Methods: This review protocol will adhere to the PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols) guidelines. The population will include health care professionals. The intervention will be the use of GenAI-enhanced teaching methods, with traditional teaching methods as the comparator. The primary outcome will be objective clinical reasoning performance, with relevant validity for the construct, population, and intended purpose. A database search will be conducted across Embase, MEDLINE, CINAHL, Scopus, and Cochrane CENTRAL, supplemented by Google Scholar, reference list, and citation searches. Study designs will include randomized controlled trials (RCTs), non-RCTs, quasiexperimental studies, and cohort studies with suitable controls. Title and abstract screening and full-text screening will be completed by 2 independent reviewers, with arbitration as required. IBM SPSS will be used to combine and calculate the overall effect. A random-effects model will be deployed, with the Hartung-Knapp-Sidik-Jonkman method used, as appropriate, to calculate the CI around the estimated pooled effect. Study heterogeneity will be assessed using I² and τ², and where studies are judged to be too diverse, results will be presented narratively. Prediction intervals will be used, if appropriate, to show how the true effect may vary between similar studies. Risk of bias will be reviewed by 2 independent reviewers, with arbitration, as required, using the Risk of Bias 2 (ROB 2) tool for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for non-RCTs, quasiexperimental studies, and interventional cohort studies. Sensitivity analysis will be used to explore possible sources of heterogeneity. A subgroup analysis may include the type and functionality of GenAI used and/or health care professional background. Results: The review was funded in September 2025. A trial search was completed on MEDLINE in December 2025, with final database searches completed in February 2026. A total of 4831 studies were retrieved, with 2083 duplicates removed. A further 2558 studies were removed at title and abstract screening, with 190 studies undergoing full-text screening and 42 studies included in the final review. Expected completion date of the final review is autumn or winter 2026. Conclusions: Health care education is rapidly adopting GenAI-enhanced teaching methods, despite inconclusive evidence on their effectiveness. The findings from this review will offer essential insight into the optimization of GenAI-enhanced teaching methods for clinical reasoning within current and future curriculum design. Trial Registration: PROSPERO CRD420261284944; https://www.crd.york.ac.uk/PROSPERO/view/CRD420261284944

An Ontology for Workplace Violence: Protocol to Support Cross-Sector Incident Reporting in Public Services

2026-10-15T12:30:20-04:00

Background: Underreporting is a defining problem in the documentation of workplace violence across public services. This is reinforced by inconsistent, often poor incident descriptions and the absence of a clear, shared nomenclature. Without an ontology-backed structure, similar events are recorded differently across settings or remain uncodable and effectively invisible. Moreover, workplace violence (WPV) is typically registered and studied within sector- and even organization-specific categories and local reporting logics rather than through a shared semantic framework, limiting comparability and cumulative understanding across sectors. To address this, we propose creating and publicizing a workplace violence ontology (WPV-ONTO) to unify the representation of WPV events across public services. Objective: The objective of this protocol is to describe and justify a research methodology for developing a cross-sector ontology and reference nomenclature for WPV in public services (WPV-ONTO), including the scoping review, expert consensus, and evaluation procedures used to build it. Promoting openness and high standards during its creation and encouraging its uptake once available are broader project goals that this protocol is designed to support, rather than measurable objectives that this protocol itself tests. Methods: Using Protégé and the METHONTOLOGY life-cycle framework, we will develop WPV-ONTO in Web Ontology Language. A methodologically defined, iterative workflow will combine (1) focused scoping searches in Web of Science, PubMed, APA PsycInfo, ERIC, and Sociological Abstracts; (2) structured extraction from established incident-reporting tools and code lists; and (3) expert consensus. Domain experts will use a hybrid top-down and bottom-up approach to define concepts, synonyms, and relationships based on iterative review of the scientific literature and sector-specific reporting structures. A pilot study with 6 to 8 frontline workers from 2 sectors will test the prototype reporting form against predefined usability criteria before version 1.0 release. Results: The primary output will be a comprehensive, versioned WPV-ONTO accommodating key WPV concepts relevant to public services, augmented with synonyms, definitions, and references. WPV-ONTO will include an explicit hierarchical structure and relations supporting inheritance and compositional incident encoding. Development will incorporate the perspectives of frontline workers, safety and aftercare professionals, policymakers, WPV researchers, and health and information-system experts. Expert-panel recruitment is planned to begin in March 2027, with version 1.0 expected after the 24-month development period. Conclusions: WPV-ONTO is expected to enable reasoning, inference, and consistent representation of relationships among WPV concepts for application in multiple contexts, including cross-sector reporting harmonization, software and API development, research data integration, and evaluation of prevention and aftercare initiatives. By providing a shared vocabulary and explicit structure, WPV-ONTO may also facilitate linkage with other relevant information systems, such as electronic medical records, and justice and police information systems, reducing methodological fragmentation and supporting coordinated cross-sector learning while retaining the contextual specificity necessary for public service environments.

Effects of Spiritual and Religious Practices on Burnout and Academic Stress Among Undergraduate Medical Students: Protocol for a Scoping Review

2026-10-15T12:30:03-04:00

Background: Burnout is increasingly recognized as a critical concern in medical education due to its associations with reduced professional performance, decreased empathy, and increased risk of medical errors. With growing evidence that medical students commonly experience burnout and its associated health consequences (eg, depression and suicide), it is essential to explore factors that may protect against its harmful effects on student well-being. Although spirituality is often considered a potential factor supporting mental health and resilience, its role in buffering burnout among medical students has not been comprehensively reviewed. Objective: This scoping review seeks to map the extent, range, and characteristics of the literature examining the relationship between spirituality and burnout and defined forms of stress among medical students. Specifically, the review will (1) describe the nature and direction of reported associations and (2) identify gaps to inform priorities for future research. Methods: This scoping review followed PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines to ensure a systematic and transparent process. Studies that examined the relationship between spirituality and burnout or related outcomes and correlates, such as anxiety, depression, stress, or suicidality, among undergraduate medical students were eligible. Only studies that focused specifically on medical students rather than other health care professionals or professional students were eligible. Eligible articles were peer-reviewed and published in English. MEDLINE (PubMed), APA PsycInfo, Scopus, and Embase databases were searched. Two reviewers independently screened titles and abstracts, followed by full-text review to determine final inclusion. Discrepancies were resolved through discussion with a third reviewer until consensus was reached. Extracted data were descriptively analyzed and summarized in charts and tables and synthesized narratively according to the review questions. Results: The database searches were completed in July 2025 and yielded 1788 records. Screening was conducted from September 2025 through January 2026. Of the database records 39 (2.2%) peer-reviewed studies met the inclusion criteria. During full-text screening, articles were most frequently excluded because they did not explicitly evaluate the association between spirituality and burnout, represented an ineligible publication type, or included populations beyond undergraduate medical students without reporting separate results for medical students. Data extraction was completed in April 2026. The manuscript reporting results was completed in May 2026 and is under review as of September 2026. Conclusions: This review will provide a comprehensive overview of how spirituality and religious practices have been examined in relation to burnout and stress among undergraduate medical students. By mapping conceptualizations and experiences of spirituality within medical training, as well as varying patterns in how these practices relate to student well-being, this review highlights key gaps in the evidence and directions for future research on factors that may support medical student mental health. Clinical Trial: OSF Registries osf.io/tqwsk; https://osf.io/tqwsk

Exploring the Neural Mechanisms of Acupuncture Stimulation in Autism Spectrum Disorder: Protocol for a Randomized, Sham-Controlled, Multimodal Neuroimaging Trial

2026-10-15T09:00:27-04:00

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted and repetitive behaviors and disturbances in social communication and interaction. Currently, there is no fundamental treatment for ASD, with only a few medications available for use on a limited basis to manage concomitant neuropsychiatric symptoms. The primary therapeutic goal of such treatments is to alleviate symptoms while maximizing the functional independence and quality of life of affected individuals. Many complementary and alternative medicine therapies have been reported to have effects on ASD symptoms; however, evidence is insufficient to confirm their clinical effectiveness. Acupuncture has traditionally been used as a complementary intervention to manage various neurological and neuropsychiatric diseases, including ASD, in East Asia. However, how acupuncture stimulation modulates neural activity at the macroscale level in individuals with ASD remains largely unknown. Objective: This study aims to elucidate disease-related brain alterations and explore the acute neural mechanisms underlying acupuncture stimulation in patients with ASD and in typically developing (TD) individuals, using a multimodal neuroimaging approach. Methods: This study was designed as a randomized, sham-controlled trial. In this stratified 2×2 design, 70 participants, including individuals with ASD (n=35) and TD controls (n=35), will each be randomly assigned to either the verum or sham acupuncture group, resulting in 4 groups. The verum acupuncture group will receive stimulation at specific acupoints clinically indicated for ASD, eliciting a deqi sensation. The sham acupuncture group will receive superficial needling at nonacupoints unrelated to ASD symptoms. Each group will undergo clinical assessments and multimodal neuroimaging measurements, including functional near-infrared spectroscopy and electroencephalography, before and after acupuncture stimulation. The primary outcome will be differences in resting state network metrics and relative band power in frontal areas by disease status. Secondary outcomes will include differences in these neural markers following acupuncture stimulation between the verum and sham groups, reflecting the group × intervention interaction. Exploratory outcomes will focus on identifying neural markers that correlate with clinical indicators of ASD. Results: Recruitment began in April 2025. To date, 23 individuals with ASD and 21 TD individuals have participated in this study. The recruitment process is expected to continue until December 2026. Conclusions: ASD presents a significant socioeconomic burden, with no definitive treatment established to date. Although acupuncture is a widely applied intervention for various neurological conditions, including ASD, its large-scale neural mechanisms remain poorly understood. By using multimodal neuroimaging, the present study aims to investigate the immediate neural substrates underlying acupuncture stimulation in patients with ASD. These findings are expected to provide a robust neurobiological foundation for future longitudinal research and the development of evidence-based integrative strategies. Trial Registration: CRIS KCT0010437; https://cris.nih.go.kr/cris/search/detailSearch.do/31192 International Registered Report Identifier (IRRID): DERR1-10.2196/97910