A Clinical Evaluation of Non-Invasive Vagus Nerve Stimulation for Temper Outbursts in People With PWS
VNS4PWS
A Phase 3, Randomized, Double-Blind, Dose-Ranging Evaluation of Transcutaneous Vagus Nerve Stimulation (tVNS) to Reduce Temper Outbursts in People With Prader-Willi Syndrome (PWS)
1 other identifier
interventional
102
1 country
18
Brief Summary
The goal of the VNS4PWS clinical study is to test the efficacy, safety, and acceptability of transcutaneous vagus nerve stimulation (tVNS) treatment in people with PWS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jan 2024
Typical duration for phase_3
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 16, 2023
CompletedFirst Posted
Study publicly available on registry
November 22, 2023
CompletedStudy Start
First participant enrolled
January 8, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
November 25, 2025
November 1, 2025
2.9 years
October 16, 2023
November 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
To determine the safety profile and tolerability of tVNS in PWS, as assessed by the frequency, severity, and seriousness of adverse events determined during the study.
Frequency, severity, and seriousness of adverse events during the study.
Through study completion, an average of 1 year
To determine the acceptability profile of tVNS in PWS as assessed by the rate of withdrawal from the study.
The acceptability profile of tVNS in PWS will be measured by the rate of withdrawal from the study.
Through study completion, an average of 1 year
To determine the acceptability profile of tVNS in PWS as assessed by the rates of device use compliance during the study.
The acceptability profile of tVNS in PWS will be measured by the rates of device use compliance throughout the study.
Through study completion, an average of 1 year
To determine the efficacy of tVNS in reducing temper outbursts in people with PWS aged 10 - 40 years.
Change in Aberrant Behavior Checklist, irritability subscale. A lower score indicates a better outcome whereas a higher score indicates a worse outcome. The minimum score is zero and the maximum score is 45.
Baseline to month 9
Secondary Outcomes (11)
To determine the efficacy of tVNS in reducing temper outbursts in people with PWS aged 10 - 40 years over the course of the study as assessed by the irritability subscale of the Aberrant Behavior Checklist.
Baseline to months 3, 6, 9.
To determine whether tVNS reduces the average number of temper outbursts per day, as assessed by the Daily Survey.
Baseline to months 3, 6, 9, and 12.
To determine whether tVNS reduces the average intensity of daily temper outbursts as measured by the Daily Survey.
Baseline to months 3, 6, 9, and 12.
To determine whether tVNS reduces the average duration of temper outbursts per day.
Baseline to months 3, 6, 9, and 12.
To determine whether tVNS decreases PWS-associated hyperphagic behaviors as measured by the Hyperphagia Questionnaire for Clinical Trials.
Baseline to months 3, 6, and 9.
- +6 more secondary outcomes
Other Outcomes (3)
Informant and self-reported measures of acceptability as assessed by a qualitative exit interview.
Through study completion, an average of 1 year.
Identification of responder characteristics as identified in a qualitative exit interview.
Through study completion, an average of 1 year.
To assess the change heart rate variability (HRV) in a subset of participants.
Through study completion, an average of 1 year.
Study Arms (2)
tVNS, Intermittent Stimulation
ACTIVE COMPARATOR28 seconds on, 32 seconds off
tVNS, Continuous Stimulation
ACTIVE COMPARATORcontinuous stimulation
Interventions
transcutaneous vagus nerve stimulation, intermittent stimulation
transcutaneous vagus nerve stimulation, continuous stimulation
Eligibility Criteria
You may qualify if:
- Genetically proven diagnosis of PWS.
- Age 10-40 years.
- History in the last six months of an average of at least two temper outbursts per week.
- Able to comply with requirements of study and provide consent or assent; If consent is to be provided by the participant's guardian, same applies to the guardian.
- Concomitant use of psychiatric medication is allowed; participant must be on a stable dose 90 days prior to screening with no plans for dose modification during the course of the study.
- Concomitant use of psychotherapy/counseling is allowed. Therapies for mental health or behavior challenges, including applied behavior analysis (ABA) are also allowed; however, participant must be on a stable regimen 90 days prior to screening with no plans for modification during the course of the study.
- Living with family or in another setting with family members or staff willing to support the participant and the required data collection.
- Agree to share tVNS patient application compliance and daily temper outburst data with the sponsor.
- Access to cellular data or Wi-Fi.
- Participant and caregiver speak American English as first language or are fluent in American English.
You may not qualify if:
- Positive pregnancy test at screening, baseline, or at any point in the study.
- Evidence of active or recent unstable serious mental illness, including, psychosis, mania, severe depression, or suicidality.
- Moved to present residential placement in last three months or less.
- Likely move in residential placement during the course of the study.
- Cardiac abnormalities including medically documented history of cardiac disease or cardiac arrhythmia, documented resting heart rate ≤ 50 beats per minute (BPM); or history of 2° type 2 or 3° heart block on electrocardiogram (ECG).
- Evidence of clinically significant abnormalities of blood, liver, or kidney function from clinical safety laboratory assessments as determined by the Site Investigator.
- History of blood clot, pulmonary embolism, or deep vein thrombosis.
- Prior diagnosis of epilepsy or currently active seizures.
- Current enrollment in the active phase of different clinical trial or interventional study.
- Current use of hearing aids or implantable medical devices including implanted vagus nerve stimulation (iVNS) device, implanted cardiac pacemaker, implanted cardiac defibrillator, cochlear implants, cerebral shunt or cardiac implantable electrical devices.
- Presence of dermal abnormalities at the stimulation site that would interfere with the ability of the tVNS device to function properly.
- Presence of an allergy to titanium, titanium-iridium, thermoplastic elastomers, perfluoroethylene propylene, or polyurethane elastomers, or components of / preservatives present in the device electrode cream (Ceteareth-20, Propylene Glycol, Bentonite, Polysorbate 20, Phenoxyethanol, Ethylhexylglycerin).
- Severe, untreated sleep apnea, as self-reported by subject or caregiver or suspected by Site Investigator.
- Subject is, in the opinion of the Investigator, not suitable to participate in the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Foundation for Prader-Willi Researchlead
- RTI Internationalcollaborator
Study Sites (18)
Stanford University
Palo Alto, California, 94304, United States
Rady Children's Hospital San Diego
San Diego, California, 92123, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Emory University
Atlanta, Georgia, 30322, United States
Rare Disease Research
Atlanta, Georgia, 30329, United States
University of Iowa
Iowa City, Iowa, 52242, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21205, United States
University of Minnesota
Minneapolis, Minnesota, 55454, United States
Children's Mercy Kansas City
Kansas City, Missouri, 64108, United States
Maimonides Medical Center
Brooklyn, New York, 11219, United States
NYU Langone Health
Garden City, New York, 11530, United States
Montefiore Medical Center and Albert Einstein College of Medicine
The Bronx, New York, 10461, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37203, United States
Christus Children'S
San Antonio, Texas, 78207, United States
University of Utah
Salt Lake City, Utah, 84108, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Theresa Strong, PhD
Foundation for Prader-Willi Research
- PRINCIPAL INVESTIGATOR
Deepan Singh, MD
Maimonides Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 16, 2023
First Posted
November 22, 2023
Study Start
January 8, 2024
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2027
Last Updated
November 25, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will not share