JMIR Publications

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, that caregiver wellbeing may act as a mediator of TAND severity, and that a wellbeing intervention designed for caregivers of children with developmental disabilities may improve caregiver wellbeing.

Objective:

The study has three aims: 1) to examine longitudinal trajectories of TAND severity in a large sample of individuals with TSC and to examine potential predictors of differential trajectories, 2) to evaluate the association between caregiver wellbeing characteristics, TAND severity and severity trajectories, and 3) to adapt and evaluate the feasibility, acceptability and potential efficacy of an ultra-brief, online group-based wellbeing intervention for family caregivers.

Methods:

For the first two aims, 500 individuals with TSC or their caregivers will be recruited in an accelerated longitudinal design to complete a TAND-SQ Checklist at five timepoints over 12 months via a web-based app. At each timepoint, participants will also complete demographic, TSC characteristics, intervention and wellbeing questionnaires. Data will be analysed using latent class mixed and multinomial regression modelling (aim 1) and structural equation and mediation modelling (aim 2). Participatory methods will be used to adapt an existing caregiver wellbeing intervention based on acceptance and commitment therapy for the TSC community (aim 3). Thereafter, 30 caregivers will participate in the adapted group-based online wellbeing intervention to assess feasibility, acceptability and potential efficacy (NCT06879665).

Results:

This study was funded in 07/2024 (HT94252410790; HT94252410791) and IRB approval was obtained from Vrije Universiteit Brussel (11/2024), University of Cape Town (07/2024) and the Department of Defense Office of Human Research Oversight (12/2024). The TAND Toolkit App has been adapted for longitudinal data collection in aims 1 and 2. ‘Soft launch’ for recruitment started in December 2025 with recruitment to continue until 500 participants are enrolled (anticipated December 2026). For aim 3, the experiential and adaptation workshops were completed in 06/2025, the pilot intervention was delivered in November 2025 and data collection will continue till May 2026.

Conclusions:

Identification of differential longitudinal TAND trajectories and their correlates will stimulate further research in TSC and generate evidence for the TAND-SQ Checklist as clinical outcome measure. Understanding the association between caregiver wellbeing and TAND severity will provide support for targeted wellbeing interventions. A successful pilot trial of a caregiver wellbeing intervention 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 to interventions for TAND. Clinical Trial: The non-randomized feasibility intervention trial, which is part of aim 3, is registered on clinicaltrials.gov (NCT06879665).