JMIR Res Protoc. 2026 May 5;15:e91726. doi: 10.2196/91726.
ABSTRACT
BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder caused by pathogenic variants in the TSC1 or TSC2 genes. Apart from multisystem physical manifestations, most individuals with TSC experience TSC-associated neuropsychiatric disorders (TAND). Little is known about how TAND severity changes over time and what factors may predict these changes. Preliminary data suggest the presence of differential TAND severity trajectories. Caregiver well-being may act as a mediator of TAND severity, and a well-being intervention designed for caregivers of children with developmental disabilities may improve caregiver well-being.
OBJECTIVE: The study aims are to (1) examine longitudinal trajectories of TAND severity in a large sample of individuals with TSC and to examine potential predictors of differential trajectories, (2) evaluate the association between caregiver well-being characteristics, TAND severity, and severity trajectories, and (3) adapt and evaluate the feasibility, acceptability, and potential efficacy of a brief, online group-based well-being intervention for family caregivers.
METHODS: For the first 2 aims, 500 individuals with TSC or their caregivers will be recruited in an accelerated longitudinal design to document TAND severity at 5 time points over 12 months via a web-based app. At each time point, participants will complete demographic, TSC characteristics, intervention, and well-being questionnaires. Data will be analyzed using latent class mixed and multinomial regression modeling (aim 1) and structural equation and mediation modeling (aim 2). Participatory methods will be used to adapt an existing caregiver well-being intervention for the TSC community (aim 3). Thirty caregivers will be invited to participate in the adapted group-based online well-being intervention.
RESULTS: This study was funded from July 2024 (HT94252410790 and HT94252410791), and ethics approvals were obtained from the University of Cape Town (July 2024), Vrije Universiteit Brussel (November 2024), and the Department of Defense Office of Human Research Oversight (December 2024). The TAND Toolkit app was adapted for longitudinal data collection (aims 1 and 2). Recruitment started in December 2025 and will continue until 500 participants are enrolled (anticipated December 2026). Primary outputs are expected by July 2028. For aim 3, experiential and adaptation workshops were completed in June 2025, the pilot intervention was delivered in November 2025, and data collection will continue till May 2026. Outputs are expected by December 2026.
CONCLUSIONS: Identification of differential longitudinal TAND trajectories and their correlates will stimulate research in TSC and generate evidence for the self-report quantified TAND checklist as a clinical outcome measure. Understanding the association between caregiver well-being and TAND severity will provide support for targeted well-being interventions. A successful pilot trial will provide preliminary data for larger-scale clinical trials, with the potential to support caregivers and improve TAND outcomes. Together, the findings from the study will help close the gap in interventions for TAND.
TRIAL REGISTRATION: ClinicalTrials.gov NCT06879665; https://clinicaltrials.gov/study/NCT06879665.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/91726.
PMID:42085697 | DOI:10.2196/91726
