Heart Rate Variability Biofeedback for Anxiety in Autistic Youth

Heart rate variability biofeedback (HRVB) is a breathing-based intervention that reduces anxiety in a range of populations. Second-generation wearable HRVB devices not only deliver scheduled biofeedback practice sessions but also allow patients to practice HRVB in-the-moment when it is needed most. This study is testing the acceptability, feasibility, and preliminary efficacy of second-generation, ambulatory HRVB for the treatment of anxiety in autistic youth.

Study Overview

• Status: Not yet recruiting
• Conditions: Anxiety; Autism Spectrum Disorder
• Intervention / Treatment: Device: Lief Smart Patch

Detailed Description

Fifty youth with autism and clinically significant anxiety will be recruited to participate in a single-arm, 8-week open-label, fully remote trial of HRVB. Participants will utilize the Lief Smart Patch which delivers HRVB training and practice through an embedded ECG monitor, accelerometer, and companion smartphone app. Specific aims of the research include: 1) Determine the acceptability and feasibility of second generation HRVB in autistic youth; and 2) Evaluate the preliminary efficacy of HRVB for the treatment of anxiety in autistic youth.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robyn P. Thom, MD; Phone Number: 781-860-1711; Email: luriecenterresearch@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 12-17 years at the time of enrollment.
2. ASD diagnosis from a qualified health professional based on medical records and confirmed based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria by the study clinician.
3. IQ ≥50 based on the Kaufman Brief Intelligence Test (KBIT-2).
4. Clinically significant anxiety, based on the Pediatric Anxiety Rating Scale (PARS) 5-item score of ≥10.
5. Stable medications for ≥30 days.
6. English speaking.
7. Willing to wear the Lief Smart Patch for 8 weeks.
8. English speaking guardian who is willing and able to complete caregiver assessments.

Exclusion Criteria:

1. Clinically significant cardiac arrhythmia based on parent report.
2. Current primary diagnosis of bipolar disorder, psychosis, substance use disorder, posttraumatic stress disorder, eating disorder, or major depressive disorder that requires a different treatment based in the opinion of the PI.
3. Acutely unstable medical/psychiatric condition (e.g. self-injury, suicidality) that would preclude study participation in the opinion of the PI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Heart rate variability biofeedback; Participants will be asked to practice HRVB for 5 minutes twice per day at times of their choosing throughout the 8-week trial. In addition to scheduled practice sessions, participants will be asked to respond to just-in-time adaptive intervention (JITAI) prompts to do brief, ~2-minute bursts of HRVB when the device senses autonomic hyperarousal. Participants will be instructed to complete ≥5 minutes per day of JITAI-delivered HRVB, self-initiated HRVB in response to self-perceived anxiety or stress, or any combination of these two practice modes.

Device: Lief Smart Patch; The Lief Smart Patch is a commercially available, noninvasive wearable heart rate variability biofeedback (HRVB) device. The patch includes an embedded electrocardiogram (ECG) sensor and accelerometer that interfaces with a companion smartphone application to deliver paced breathing exercises and just-in-time adaptive intervention (JITAI) prompts. It is an externally worn patch that temporarily adheres to the skin surface and can be removed by the participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 8-Week Change in Pediatric Anxiety Rating Scale (PARS) 5-Item Total Score	The PARS, a clinician-administered measure of child anxiety symptom severity based on both patient and parent-report will be the primary outcome measure. It has demonstrated inter-rater and test-retest reliability, and has previously been used by our group as the primary outcome measure in a RCT of mirtazapine for anxiety in youth with ASD, demonstrating sensitivity to change. The 5-item PARS score will be the primary outcome measure for this trial. Scaled score ranges from 0-25 with higher scores indicating more severe anxiety symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants who Responded to Treatment at 8 Weeks According to the Improvement Item of the Clinical Global Impression-Improvement (CGI-I) (Response Defined as CGI-I = 1 or 2)	The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scales indicating improvement (1=very much improved; 2=much improved). In this study, the CGI-I will be focused on the target symptom of anxiety.	Week 4, Week 8. Week 8 score reported.
Mean 8-Week Change in Clinical Global Impression Severity Subscale (CGI-S)	The CGI-S is rated on a scale from 1 to 7, where 1 = normal, not at all ill; 3 = mildly ill; 5 = markedly ill; 7 = among the most extremely ill patients. The CGI-S will be rated based on the severity of anxiety symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported.
Mean 8-Week Change in Parent-Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD) Score	The PRAS-ASD is a novel parent-rated 25-item scale with demonstrated reliability and validity. Scores range from 0-75, with higher scores indicating more severe parent-rated anxiety.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported.
mHealth App Usability Questionnaire (MAUQ) Standalone Apps for Patients	Mean Likert rating on the mHealth App Usability Questionnaire (MAUQ) Standalone Apps for Patients. The MAUQ includes 18 questions, each rated on a Likert scale of 1-7. Total scores range from 18-126, with higher scores indicating increased usability.	Week 8
Feasibility	Proportion of enrolled youth meeting the scheduled daily practice criterion (≥50% study days with ≥5 minutes combined JITAI-delivered and self-initiated HRVB practice).	Week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 8-Week Change in Aberrant Behavior Checklist (ABC-2) Irritability Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Irritability Subscale is derived from 15 items, with a score range from 0-45, where higher scores indicate more severe irritability.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Aberrant Behavior Checklist (ABC-2) Lethargy/Social Withdrawal Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Lethargy/Withdrawal Subscale is derived from 16 items, with a score range from 0-48 where higher scores indicate more severe Lethargy/Withdrawal symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Aberrant Behavior Checklist (ABC-2) Stereotypic Behavior Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Stereotypic Behavior Subscale is derived from 7 items, with a score range of 0-21 where higher scores indicate more severe stereotypic behaviors.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Aberrant Behavior Checklist (ABC-2) Hyperactivity Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Hyperactivity Subscale is derived from 16 items with a score range of 0-48, where severe scores indicate more severe hyperactivity symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Aberrant Behavior Checklist (ABC-2) Inappropriate Speech Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Inappropriate Speech Subscale is derived from 4 items with a score range of 0-12, where higher scores indicate more severe Inappropriate Speech symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) Score	The ADHD-RS is an 18-question, parent-rated assessment reflecting DSM symptoms of ADHD. The score range is 0-54, with higher scores indicating more severe ADHD symptoms.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 reported
Mean 8-Week Change in Children's Sleep Habits Questionnaire (CSHQ) Total Score	The CSHQ is a 52-question parent survey used to assess sleep difficulties. 33 items are used to generate the total score, which ranges from 33-99, with a cutoff of >41 suggesting clinically significant sleep problems. Higher scores are indicative of more severe sleep problems.	Baseline, Week 4, Week 8; Change from Baseline to Week 8 is reported

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Eagles Autism Foundation

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: September 4, 2026
• First Submitted That Met QC Criteria: September 4, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: autism spectrum disorder; anxiety; heart rate variability biofeedback; Lief
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Anxiety Disorders
• Other Study ID Numbers: 2026P001463

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes