Evaluating the potential of respiratory-sinus-arrhythmia biofeedback for reducing physiological stress in adolescents with autism: a protocol for a randomized controlled study

BackgroundPrior evidence points towards lower cardiac vagal modulation in individuals with Autism Spectrum Disorder (ASD) as compared to control groups. A cross-sectional phase in this study will gather more evidence concerning this topic. A longitudinal phase will explore the efficacy of a biofeedback intervention based on Respiratory Sinus Arrhythmia (RSA) in adolescents with ASD. Finally, a feasibility study will focus on a non-supervised RSA biofeedback intervention in this population. MethodsThe cross-sectional phase includes the comparison of adolescents with ASD (n=38) and age and gender matched typically developing peers. A standardized assessment will be used which contains physiological, cortisol and behavioral measurements. The longitudinal phase contains a randomized, single-blinded and sham-controlled design to determine the efficacy of supervised RSA biofeedback in adolescents with ASD (n=128). A follow-up phase of 5 weeks is included to evaluate the presence of retention effects. During the latter, a feasibility study will focus on a non-supervised intervention (n=62). Assessments as described previously are scheduled after the intervention and the follow-up phase. DiscussionFirst, more conclusive evidence will be provided for the presence of lower cardiac vagal modulation in adolescents with ASD as well as the association between these lower values and physiological and behavioral indices. Second, the supervised intervention in adolescents with ASD is hypothesized to upregulate this cardiac vagal modulation and positively change behavioral and physiological parameters. Third, evidence regarding the feasibility and acceptability of a non-supervised intervention may open novel avenues for home-based interventions in this population. Study registrationClinicalTrials.gov, NCT04628715. Registered on 13 November 2020. DeclarationsO_ST_ABSFundingC_ST_ABSFunding is provided by the Marguerite-Marie Delacroix foundation with grant number GV/B-363. The funder will not have any role in any part of this study. Competing interestsThe authors declare that they have no conflict of interest. Availability of data and materialAll data from the participants will be de-identified and provided with a unique code. The coded data will be stored for 20 years in secured databases of the Research Group for Adapted Physical Activity and Psychomotor Rehabilitation, protected by the KU Leuven and will only be accessible by researchers of collaborating labs. The key to the coded data will be stored securely and confidentially in a separate electronic file. The saliva samples will be stored under appropriate conditions during the study at the biobank of the KU Leuven and will be destroyed afterwards. Participants waive any intellectual property rights on findings that might result from the analysis of their saliva samples. Code availabilityNot applicable. Authors contributionsAll authors contributed to the writing of this manuscript and the grant proposal. Anoushka Thoen leads the study and data management under supervision of Tine Van Damme, who provided facilities and equipment. All authors read and approved the final manuscript. Ethics approvalEthical approval for this study was granted by both the Ethics Committee UPC KU Leuven on July 2nd 2020 (ref. EC2020-541, version 2.0) and the Ethics Committee Research UZ/KU Leuven on October 20th 2020 (ref: S64219, version 1.0). Consent to participateParents of the participants should provide informed consent in addition to the informed assent provided by the participants themselves. Participants may withdraw consent and participation at any time. The participants request to withdraw from the study will always be respected and reasons to withdraw are not obliged to be mentioned. The sponsor of this study is KU Leuven (Oude Markt 13, 3000 Leuven, Belgium) and will have no role in any part of this study. Consent for publicationAuthorship to publications will be determined in accordance with the requirements published by the International Committee of Medical Journal Editors and in accordance with the requirements of the respective peer-reviewed medical journal. AmendmentsEvery substantial adjustment to the protocol will be communicated to the Ethics Committee UPC KU Leuven and the Ethics Committee Research UZ/KU Leuven as an amendment to the protocol. Only after approval of this amendment, the adjustments can be implemented and communicated to the researchers and participants. AuditingThe researchers will permit study-related monitoring, audits, Ethical Committee review and regulatory inspection, providing direct access to all related source data/documents. Dissemination of study resultsThe results of this study will be used for publication in peer-reviewed journals. There will also be a general dissemination of the study results for the participants and personal results will be provided upon request.