Autism Spectrum DisorderNCT04628715
Biofeedback Intervention in Adolescents With Autism Spectrum Disorder
A study testing RSA biofeedback in people with Autism Spectrum Disorder, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- RSA biofeedback
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteBelgium
- Study dates
- 26 Nov 2020to 30 Nov 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Written informed consent/assent
- Male/female
- 13-18 years old
- For adolescents with ASD only: Confirmed ASD-diagnosis (DSM-IV/V)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating the Potential of Respiratory-sinus-arrhythmia Biofeedback for Reducing Physiological Stress in Adolescents With Autism: a Randomized Controlled Study
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.
Read the 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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- RSA biofeedback
- Keywords
- Biofeedback, Stress
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSA biofeedbackDevice
Biofeedback intervention based on breathing at resonance frequency
| Study group | Role | What they receive |
|---|---|---|
| Supervised RSA biofeedback | Experimental | 5 weeks with weekly supervised sessions of 30 minutes and daily home practice sessions of 20 minutes. The latter sessions can be divided into four bouts of 5 minutes which can be spread across the day. The main goal during this intervention is to breath at resonance frequency which is slower than the usual breathing frequency. Participants will be guided towards this lower breathing frequency by using appropriate breathing techniques and the provision of a breathing pacer during the supervised sessions. During home practice, the participants will be provided with an application which will visualise a breathing pacer at their resonance frequency. At the third session, participants will no longer receive a breathing pacer but are instructed to breath in phase with their heart rate which is visualised on the computer screen instead of the breathing pacer. Receives: Device: RSA biofeedback |
| Supervised sham RSA biofeedback | Sham comparator | 5 weeks with weekly supervised sessions of 30 minutes and daily home practice sessions of 20 minutes. The latter sessions can be divided into four bouts of 5 minutes which can be spread across the day. The sham-control treatment will follow the same steps as outlined in the supervised intervention arm. However, the participants in this control group will not receive any information regarding their own heart rate and they will not practice at their resonance frequency. Instead, a default mode will be shown during the sessions and in their application for home practice. Receives: Device: RSA biofeedback |
| Non-supervised RSA biofeedback | Experimental | 1 short guided session (30 minutes) and daily practice (20 minutes; 4 bouts of 5 minutes) for 5 weeks. The biofeedback protocol will be provided by an application, similar to the supervised protocol but without guidance throughout the sessions, except for the first session. During this first session, the information will be provided about the application and the heart rate sensor (Polar band) which will detect changes in heart rate during the training. In addition, the resonance frequency of the participant will be determined so they can practice breathing at this frequency for the next 5 weeks. Receives: Device: RSA biofeedback |
| No intervention | No intervention | No intervention is given. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Root Mean Square of Successive Differences between normal heart beats (RMSSD) as a measure of cardiac vagal modulation.
This measure will provide information concerning the cardiac vagal modulation of heart rate based on time domain analysis. This analysis will be performed based on heart rate recordings at multiple assessment timepoints (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
Change in Logarithm of High-Frequency Heart Rate Variability (LnHF-HRV) as a measure of cardiac vagal modulation.
This measure is an additional primary outcome measure concerning cardiac vagal modulation of heart rate based on frequency domain analysis. This analysis will be performed based on heart rate recordings at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
Secondary outcomes (15)
Change in Heart rate
Physiological assessment of heart rate by using a ECG-monitoring with 3 electrodes placed on the chest. The unit measure will be expressed in beats per minute. The sensors and biofeedback device from 'nexus-10' will be used in combination with 'biotrace+' software. This measurement will be repeated at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: 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
Change in Breathing frequency
Physiological assessment of the breathing pattern by using an elastic band with stretch-sensitive sensors around the waist. The unit measure will be expressed in breaths per minute. The sensors and biofeedback device from 'nexus-10' will be used in combination with 'biotrace+' software. This measurement will be repeated at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: 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
Change in Skin conductance
Physiological assessment of skin conductance by placing one sensor on the palmar side of the index finger and 1 on the palmar side of the ring finger. The unit measure will be expressed in Micro Siemen. The sensors and biofeedback device from 'nexus-10' will be used in combination with 'biotrace+' software. This measurement will be repeated at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: 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
Change in Fingertip temperature
Physiological assessment of the temperature of the fingertip by attaching a temperature sensor on the palmar side of the middle finger. The unit measure will be expressed in Degrees Celsius.The sensors and biofeedback device from 'nexus-10' will be used in combination with 'biotrace+' software. This measurement will be repeated at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Measured: 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
Change in Cortisol level
Endogenic measurement of cortisol level in saliva samples (3 times during assessment procedure for both adolescent groups, with and without autism spectrum disorder). These 3 measurements will be repeated at multiple assessment points (only for adolescents with autism spectrum disorder).
Measured: 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
Autism Spectrum Quotient - Adolescent Version (AQ)
Identifies the extent of autistic traits shown by a person of normal intelligence based on parent-report. The scale's total score can vary between 0 and 50 in which a higher score means a higher presence of symptoms related to the autism spectrum. A cut-off of 32 is used for the in- or exclusion of typically developing adolescents. This measure will only be used once in both adolescent groups (with and without autism spectrum disorder).
Measured: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder)
Change on Social Responsiveness Scale - 2nd edition (SRS-2)
A quantitative assessment of the severity of autism traits during the past six months in children based on parent-report. This questionnaire identifies social impairment associated with ASD and quantifies its severity by using 5 subscales (Social Awareness, Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior). The total score can vary between 65 and 260. These scores are related to t-values from the questionnaires manual. Higher scores are related to a higher level of impairment. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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)
Change on Repetitive Behavior Scale - Revised (RBS-R)
Scores the number and intensity of repetitive and restrictive behaviors of the past month in children based on parent-report. The scale's maximum score varies between 0 and 129 with higher scores relating to a higher presence of repetitive and restrictive behaviors. These behaviors are additionally categorised in 6 categories: Stereotyped Behavior; Self-injurious Behavior; Compulsive Behavior; Ritualistic Behavior; Sameness Behavior. Parent are also asked to rate the impact of these behaviors on daily functioning on a scale from 0 (meaning no interference with daily life) and 100 (extremely problematic related to functioning in daily life). Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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)
Change on Strengths and Difficulties Questionnaire - parent report (SDQ-PR)
A brief behavioral screen in which parents need to rate the presence of certain behaviors in their child during the past six months or during the past academic year. There are 5 categories of behavioral problems: emotional problems, conduct problems, hyperactivity, peer problems and prosocial behavior. The scale's total score varies between 0 and 40 with higher values indicating more behavioral problems and consists of the summation of all scales except the prosocial scale score. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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)
Change on Strengths and Difficulties Questionnaire - adolescent self-report (SDQ-SR)
A brief behavioral screen to rate the presence of certain behaviors during the past six months, based on adolescent self-report. There are 5 categories of behavioral problems: emotional problems, conduct problems, hyperactivity, peer problems and prosocial behavior. The scale's total score varies between 0 and 40 with higher values indicating more behavioral problems and consists of the summation of all scales except the prosocial scale score. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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)
Change on Perceived Stress Scale - Adolescent version (PSS)
Measures the degree to which situations in the adolescent's life are appraised as stressful, that is, how unpredictable, uncontrollable, and overloaded respondents find their lives. This measure is based on adolescent self-report and items are adapted according to the specific problems adolescents can encounter in their lives such as school-related stress. The scale's total score varies between 0 and 40 in which higher scores relate to higher perceived stress levels. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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
Change on Depression Anxiety and Stress Scale-21 items version
Measures the presence of symptoms of depression, anxiety and stress based on adolescent self-report. The scale's total score varies between 0 and 63 in which higher scores relate to a higher presence of symptoms. Separate scale scores are calculated for symptoms related to depression, anxiety and stress. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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
Change on Physical Activity Vital Sign
Measures the level of physical activity of the last week based on adolescent self-report. This measures consists of two short questions related to (1) the amount of days the adolescent was physically active and (2) the amount of minutes (on average) this psychical activity was endured. Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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
Change on Visual Analogue Scale (VAS) for sensory hyper-responsivity
Measures the self-reported impact of sensory hyper-responsivity of the adolescent on a Visual Analogue Scale going from 0 (meaning no perceived sensory hyper-responsivity) to 100 (meaning presence of severe sensory hyper-responsivity and negative impact on functioning). Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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
Change on Visual Analogue Scale for perceived stress
To rate the self-reported perceived stress-level of the adolescent on a Visual Analogue Scale per stressor during the stress-inducing test. The scale score can vary between 0 (meaning no stress) and 100 (meaning highest level of perceived stress possible). Change in score for this outcome measure is only measured in adolescents with autism spectrum disorder.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2020
- Study start26 Nov 2020
- Primary completion30 Nov 2022
- Study completion30 Nov 2022
Why it stopped: Recruitment has finished in November 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tine Van Damme, Professor, Principal investigator, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04628715
- Sponsor's protocol ID
- s64219
- Status last verified
- May 2022
- First submitted
- 6 Nov 2020
- Last updated
- 30 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Thoen A, Alaerts K, Prinsen J, Steyaert J, Van Damme T. The Physiological and Clinical-Behavioral Effects of Heart Rate Variability Biofeedback in Adolescents with Autism: A Pilot Randomized Controlled Trial. Appl Psychophysiol Biofeedback. 2024 Sep;49(3):419-438. doi: 10.1007/s10484-024-09638-1. Epub 2024 Mar 15.
PubMed 38491260Thoen 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.
PubMed 34674737
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Potential of Respiratory-sinus-arrhythmia Biofeedback for Reducing Physiological Stress in Adolescents With Autism: a Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT04628715
- Acronym / sponsor ID
- s64219
- Conditions
- Autism Spectrum Disorder
- Keywords
- Biofeedback, Stress
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment has finished in November 2022
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 26 Nov 2020 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 30 Nov 2022 (actual)
- First posted
- 13 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Supervised RSA biofeedback | Experimental | Device: RSA biofeedback5 weeks with weekly supervised sessions of 30 minutes and daily home practice sessions of 20 minutes. The latter sessions can be divided into four bouts of 5 minutes which can be spread across the day. The main goal during this intervention is to breath at resonance frequency which is slower than the usual breathing frequency. Participants will be guided towards this lower breathing frequency by using appropriate breathing techniques and the provision of a breathing pacer during the supervised sessions. During home practice, the participants will be provided with an application which will visualise a breathing pacer at their resonance frequency. At the third session, participants will no longer receive a breathing pacer but are instructed to breath in phase with their heart rate which is visualised on the computer screen instead of the breathing pacer. |
| Supervised sham RSA biofeedback | Sham comparator | Device: RSA biofeedback5 weeks with weekly supervised sessions of 30 minutes and daily home practice sessions of 20 minutes. The latter sessions can be divided into four bouts of 5 minutes which can be spread across the day. The sham-control treatment will follow the same steps as outlined in the supervised intervention arm. However, the participants in this control group will not receive any information regarding their own heart rate and they will not practice at their resonance frequency. Instead, a default mode will be shown during the sessions and in their application for home practice. |
| Non-supervised RSA biofeedback | Experimental | Device: RSA biofeedback1 short guided session (30 minutes) and daily practice (20 minutes; 4 bouts of 5 minutes) for 5 weeks. The biofeedback protocol will be provided by an application, similar to the supervised protocol but without guidance throughout the sessions, except for the first session. During this first session, the information will be provided about the application and the heart rate sensor (Polar band) which will detect changes in heart rate during the training. In addition, the resonance frequency of the participant will be determined so they can practice breathing at this frequency for the next 5 weeks. |
| No intervention | No intervention | –No intervention is given. |
Who may qualify
- Ages
- 13 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Written informed consent/assent
- Male/female
- 13-18 years old
- For adolescents with ASD only: Confirmed ASD-diagnosis (DSM-IV/V)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSA biofeedbackBiofeedback intervention based on breathing at resonance frequency | Device | Non-supervised RSA biofeedback, Supervised RSA biofeedback, Supervised sham RSA biofeedback |
Primary outcome
Change in Root Mean Square of Successive Differences between normal heart beats (RMSSD) as a measure of cardiac vagal modulation.
Time frame: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
This measure will provide information concerning the cardiac vagal modulation of heart rate based on time domain analysis. This analysis will be performed based on heart rate recordings at multiple assessment timepoints (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
Change in Logarithm of High-Frequency Heart Rate Variability (LnHF-HRV) as a measure of cardiac vagal modulation.
Time frame: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up
This measure is an additional primary outcome measure concerning cardiac vagal modulation of heart rate based on frequency domain analysis. This analysis will be performed based on heart rate recordings at multiple assessment points (only for adolescents with autism spectrum disorder). In addition, during one assessment, change will be measured between the different tasks (baseline, stroop word-color interference task, rest, social stress recall task and rest) in both adolescent groups (with and without autism spectrum disorder).
15 secondary outcomes
Change in Heart rate
Time frame: 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
Change in Breathing frequency
Time frame: 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
Change in Skin conductance
Time frame: 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
Change in Fingertip temperature
Time frame: 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
Change in Cortisol level
Time frame: 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
Autism Spectrum Quotient - Adolescent Version (AQ)
Time frame: At baseline assessment (typically developing adolescents + adolescents with autism spectrum disorder)
Change on Social Responsiveness Scale - 2nd edition (SRS-2)
Time frame: 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)
Change on Repetitive Behavior Scale - Revised (RBS-R)
Time frame: 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)
Change on Strengths and Difficulties Questionnaire - parent report (SDQ-PR)
Time frame: 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)
Change on Strengths and Difficulties Questionnaire - adolescent self-report (SDQ-SR)
Time frame: 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)
Change on Perceived Stress Scale - Adolescent version (PSS)
Time frame: 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
Change on Depression Anxiety and Stress Scale-21 items version
Time frame: 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
Change on Physical Activity Vital Sign
Time frame: 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
Change on Visual Analogue Scale (VAS) for sensory hyper-responsivity
Time frame: 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
Change on Visual Analogue Scale for perceived stress
Time frame: 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
Results and safety
The study was stopped early (reason given: Recruitment has finished in November 2022). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
- Derived from this study: PubMed 38491260Thoen A, Alaerts K, Prinsen J, Steyaert J, Van Damme T. The Physiological and Clinical-Behavioral Effects of Heart Rate Variability Biofeedback in Adolescents with Autism: A Pilot Randomized Controlled Trial. Appl Psychophysiol Biofeedback. 2024 Sep;49(3):419-438. doi: 10.1007/s10484-024-09638-1. Epub 2024 Mar 15.
- Derived from this study: PubMed 34674737Thoen 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.
- Information on research project on the Leuven Autism Research group webpageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tine Van Damme, Professor principal investigator
KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing RSA biofeedback in people with Autism Spectrum Disorder, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Recruitment has finished in November 2022). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Root Mean Square of Successive Differences between normal heart beats (RMSSD) as a measure of cardiac vagal modulation. (time frame: At all assessment points: before supervised intervention (baseline) + after 5 weeks supervised intervention + after 5 weeks follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04628715, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023.