Clinical trial NCT04628715: Biofeedback Intervention in Adolescents With Autism Spectrum Disorder
Official title: Evaluating the Potential of Respiratory-sinus-arrhythmia Biofeedback for Reducing Physiological Stress in Adolescents With Autism: a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Biofeedback
Stress
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2020-11-13
Enrollment: 63
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There are two intervention phases, a supervised intervention and a feasibility study for a non-supervised intervention (during the follow-up phase after the supervised intervention).

During the supervised intervention (5weeks), participant will be randomly allocated to the RSA biofeedback intervention (1) or a sham-control intervention (2). Then a 5-week follow-up phase is included during which the feasibility study of a non-supervised RSA biofeedback intervention will take place. The two groups from the supervised intervention will each be split into two (a and b) where groups 1a and 2a will receive a non-supervised biofeedback intervention and groups 1b and 2b will receive no intervention. Allocation to groups a and b is also ad random. Important to note: only during the supervised intervention, blinding of participants is possible whereas during the non-supervised intervention, this is not feasible.
Primary purpose: TREATMENT

Brief summary: This study consists of two phases, a cross-sectional and a interventional. The cross-sectional phase will provide more insight into the differences in the autonomic functioning between adolescents with autism spectrum disorder and their typically developing peers. During the longitudinal phase, the efficacy of an RSA biofeedback intervention will be examined in adolescents with autism spectrum disorder.

Detailed description: In recent years, numerous studies have investigated the potential contributing role of the autonomic nervous system (ANS) in psychiatric disorders, including autism spectrum disorder (ASD). One of the most commonly adopted physiological parameters for assessing ANS functioning in psycho-physiological research is based on the assessment of heart rate variability (HRV). The heart's pacemaker is controlled by both the sympathetic and the parasympathetic nervous system, which results in the natural variation of the interval between heart beats. One important component of HRV is commonly known as respiratory sinus arrhythmia (RSA). This component is solely mediated by the parasympathetic subsystem through direct projections of the vagus nerve from the brain stem to the heart and is therefore also known as an index of cardiac vagal modulation. The term RSA is adopted since it defines the phenomenon of the relation between heart rate variability and the respiratory cycle in certain circumstances. The clinical importance of RSA has been reported in multiple studies as higher RSA is associated with higher cognitive abilities, effective social behavior, fewer internalizing symptoms (e.g. anxiety and depression) and appropriate emotion regulation. In addition, lower RSA has been linked to conduct problems, trait hostility, anxiety disorders and depression. With respect to children and adolescents with ASD, several studies have investigated the ANS functioning by assessing RSA during various activities (e.g. cognitive tasks, non-social auditory tasks, social cognition tasks and social interaction tasks) as well as during resting situations. While some studies revealed no significant differences in RSA levels between ASD and typically developing (TD) peers, the majority of studies seemed to converge on demonstrating lower levels of RSA in patients with ASD. Furthermore, in these studies, lower RSA levels in ASD were associated with more social problems, internalizing problems, higher levels of anxiety, problems with emotional control, the presence of more severe visual and/or auditory sensory problems and the presence of repetitive and restrictive behaviors. In line with the link between lowered RSA and more psychological and social problems, it has been posited that it would be of great relevance to develop and validate an intervention that specifically targets the up-regulation of RSA-values, or the cardiac vagal modulation, in individuals with ASD . To do so, biofeedback-based interventions have been put forward as these involve the recording of physiological signals (e.g. RSA or skin conductance) which are transformed into visual (or auditory) presentations and subsequently provided to the individual as direct feedback. This visualisation of ongoing bodily sensations would provide an added value for individuals with ASD, as previous studies have reported a lower ability to consciously perceive internal bodily sensations (interoceptive awareness) in this population. Considering that adolescence is a vulnerable period with rapid changes in distinct developmental domains, this population will be targeted during this research project. As previously mentioned, the clinical importance of RSA in both typically developing populations and populations with ASD has already been demonstrated. However, due to methodological differences, these studies are frequently incomparable and/or often lead to conflicting evidence. Therefore, a cross-sectional phase will be conducted first in this research project in which adolescents with and without ASD will be recruited. In this phase, they will perform a stress-inducing test in which physiological, endogenic and behavioral data will be collected. The main focus of this first part is on RSA in which lower RSA-values are hypothesized in adolescents with ASD as compared to their typically developing peers, based on previously mentioned study results. The second part of this research project consists of the evaluation of an RSA-based biofeedback approach for the up-regulation of RSA in adolescents with ASD. In other words, we will explore the potential of this intervention for enhancing cardiac vagal modulation and the influence on behavioral problems related to lower RSA in individuals with ASD as determined in previous research and based on findings during the first part of this study. Importantly, the validation of an RSA biofeedback intervention for adolescents with ASD may open novel avenues for home-based interventions in this population where therapist contact can be limited and integration into the daily routine can be supported using biofeedback apps. In addition, the current worldwide circumstances due to the corona virus disease has provided clinicians with new and useful information regarding their patients with ASD as these patients perceived the increase of home-based interventions as something positive. Therefore, the biofeedback intervention in this research project may have an additional advantage due to its home-based approach. Finally, the promising results of RSA biofeedback interventions in clinical populations, including ASD, are reported in various domains, going from decrements in anxiety and depression symptoms to improvements of social functioning. Therefore, this intervention may be valuable for adolescents with ASD given their vulnerable position in development.

Eligibility criteria: Inclusion Criteria:

* Written informed consent/assent
* Male/female
* 13-18 years old
* For adolescents with ASD only: Confirmed ASD-diagnosis (DSM-IV/V)

Exclusion Criteria:

* Presence of intellectual disability (DSM-IV/V)
* Hearing- or vision impairment without appropriate correction
* Presence of congenital heart diseases, diagnosed cardiovascular abnormalities or somatic diseases
* Pregnancy
* Insufficient knowledge of Dutch language
* Participation in other Clinical Trial(s)
* For typically developing adolescents only: Presence of neurodevelopmental disorder or psychiatric disorder (DSM-IV/V) + Presence of a sibling with a neurodevelopmental disorder (DSM-IV/V)

Primary outcomes:
measure: Change in Root Mean Square of Successive Differences between normal heart beats (RMSSD) as a measure of cardiac vagal modulation.
timeFrame: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
measure: Change in Logarithm of High-Frequency Heart Rate Variability (LnHF-HRV) as a measure of cardiac vagal modulation.
timeFrame: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
Secondary outcomes:
measure: Change in Heart rate
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change in Breathing frequency
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change in Skin conductance
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change in Fingertip temperature
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change in Cortisol level
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Autism Spectrum Quotient - Adolescent Version (AQ)
timeFrame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder)
measure: Change on Social Responsiveness Scale - 2nd edition (SRS-2)
timeFrame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder) + after follow-up phase at the end of the trial (adolescents with autism spectrum disorder)
measure: Change on Repetitive Behavior Scale - Revised (RBS-R)
timeFrame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder) + after follow-up phase at the end of the trial (adolescents with autism spectrum disorder)
measure: Change on Strengths and Difficulties Questionnaire - parent report (SDQ-PR)
timeFrame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder) + after follow-up phase at the end of the trial (adolescents with autism spectrum disorder)
measure: Change on Strengths and Difficulties Questionnaire - adolescent self-report (SDQ-SR)
timeFrame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder) + after follow-up phase at the end of the trial (adolescents with autism spectrum disorder)
measure: Change on Perceived Stress Scale - Adolescent version (PSS)
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change on Depression Anxiety and Stress Scale-21 items version
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change on Physical Activity Vital Sign
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change on Visual Analogue Scale (VAS) for sensory hyper-responsivity
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
measure: Change on Visual Analogue Scale for perceived stress
timeFrame: Adolescents with autism spectrum disorder: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up; TD adolescents: baseline only
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: KU Leuven
state: Vlaams Brabant
Study officials:
affiliation: KU Leuven
name: Tine Van Damme, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thoen A, Steyaert J, Alaerts K, Van Damme T. Evaluating the potential of respiratory-sinus-arrhythmia biofeedback for reducing physiological stress in adolescents with autism: study protocol for a randomized controlled trial. Trials. 2021 Oct 21;22(1):730. doi: 10.1186/s13063-021-05709-4.