Prader-Willi SyndromePhase 3VNS4PWSNCT06144645
A Clinical Evaluation of Non-Invasive Vagus Nerve Stimulation for Temper Outbursts in People With PWS
A Phase 3 study testing tVNS, intermittent stimulation and tVNS, continuous stimulation in people with Prader-Willi Syndrome, run by Foundation for Prader-Willi Research at 18 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 40 years
- Conditions the study is for
- Prader-Willi Syndrome
- What is being tested?
- tVNS, intermittent stimulation and tVNS, continuous stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 18 sitesUnited States
- Study dates
- 8 Jan 2024to 1 Apr 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 10 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Emory University
Atlanta, Georgia, 30322
Rare Disease Research
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21205
Maimonides Medical Center
Brooklyn, New York, 11219
University of Virginia
Charlottesville, Virginia, 22908
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
NYU Langone Health
Garden City, New York, 11530
University of Iowa
Iowa City, Iowa, 52242
Children's Mercy Kansas City
Kansas City, Missouri, 64108
University of Minnesota
Minneapolis, Minnesota, 55454
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
Stanford University
Palo Alto, California, 94304
University of Utah
Salt Lake City, Utah, 84108
Christus Children'S
San Antonio, Texas, 78207
Rady Children's Hospital San Diego
San Diego, California, 92123
Montefiore Medical Center and Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: 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)
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.
Read the detailed description
The main questions the VNS4PWS study seeks to answer are: (1) is tVNS treatment safe in people with PWS, (2) is tVNS treatment acceptable to people with PWS, and (3) is tVNS an effective treatment to reduce temper outbursts in people with PWS. Participants will wear the tVNS device daily for 4 hours over a period of 9 months. Two different doses of tVNS will be compared. During the final three months of the trial, the effect of stopping treatment will be studied. After the first year of the study, participants will have the opportunity to continue on to a 1-year open label extension period during which active tVNS treatment will be resumed.
- Conditions
- Prader-Willi Syndrome
- Being tested
- tVNS, intermittent stimulation, tVNS, continuous stimulation
- Keywords
- Prader-Willi syndrome, PWS, Prader
- Medical subject headings
- Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tVNS, intermittent stimulationDevice
Also called tVNS R, manufactured by tVNS Technologies, intermittent stimulation
transcutaneous vagus nerve stimulation, intermittent stimulation
tVNS, continuous stimulationDevice
Also called tVNS R, manufactured by tVNS Technologies, continuous stimulation
transcutaneous vagus nerve stimulation, continuous stimulation
| Study group | Role | What they receive |
|---|---|---|
| tVNS, Intermittent Stimulation | Active comparator | 28 seconds on, 32 seconds off Receives: Device: tVNS, intermittent stimulation |
| tVNS, Continuous Stimulation | Active comparator | continuous stimulation Receives: Device: tVNS, continuous stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
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.
Measured: 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.
The Daily Survey will collect caregiver-reported data on the number of temper outbursts per day. A lower score indicates a better outcome and a higher score indicates a worse outcome. The minimum daily score is zero and the maximum daily score that the scale can capture is 20.
Measured: 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.
The Daily Survey will collect caregiver-reported data on the intensity of daily temper outbursts. A higher score indicates a worse outcome and a lower score indicates a better outcome. The minimum score is 1 and the maximum score is 7.
Measured: Baseline to months 3, 6, 9, and 12.
To determine whether tVNS reduces the average duration of temper outbursts per day.
The Daily Survey will collect caregiver-reported data on the duration of daily temper outbursts. The minimum score is 1 and the maximum score is 7.
Measured: 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.
Stimulation of the vagus nerve may impact hyperphagic drive. It may also impact eating behaviors and the ability of the person with PWS to cope with eating restrictions. Higher scores indicate a worse outcome and lower scores indicate a better outcome. The minimum score is 0 and the maximum score is 36.
Measured: Baseline to months 3, 6, and 9.
To determine whether tVNS treatment decreases skin picking in PWS, as assessed by the Self Injury Trauma Scale.
The Self Injury Trauma Scale is a widely used method for quantifying surface tissue damage caused by self-injurious behavior. A lower score indicates a better outcome and a higher score indicates a worse outcome. The minimum score is 1 and the maximum is 5.
Measured: Baseline to months 3, 6, and 9.
To determine whether tVNS decreases anxiousness and distress in PWS as measured by the PWS Anxiousness and Distress Questionnaire.
tVNS may impact behaviors associated with anxiousness and distress, which are common in PWS. A lower score indicates a better outcome and a higher score indicates a worse outcome. The minimum score is 0 and the maximum is 56.
Measured: Change in PWS Anxiousness and Distress Questionnaire at baseline and months 3, 6, and 9.
To determine whether reductions in temper outbursts result in reduced caregiver burden as measured by the Zarit Burden Interview.
Reduction in outbursts is expected to positively impact other members of the participant's family - this measure may reflect improvements in family relationships. A higher score indicates a worse outcome. A lower score indicates a better outcome. The minimum score is 0 and the maximum score is 88.
Measured: Change in Zarit Burden Interview (ZBI) between baseline and month 9.
To determine whether reductions in temper outburst is associated with improved quality of life as measured by the Parent Proxy Global Health 7.
Reduction in outbursts is expected to meaningfully improve quality of life as assessed by the Parent Proxy Global Health 7. A higher score indicates a better outcome and a lower score indicates a worse outcome. The minimum score is 7. The maximum score is 35.
Measured: Change in Parent Proxy Global Health 7 from baseline to months 3, 6, 9.
To assess whether overall disease severity is improved as measured by the Change in the Clinical Global Impression of disease severity.
This measure will serve as an anchor to assess the meaningfulness of reductions in temper outbursts. A lower score indicates a better outcome. A higher score indicates a worse outcome. The maximum score is 7. The minimum score is 1.
Measured: Change in the Clinical Global Impression of disease severity at baseline and months 3, 6, 9.
To assess whether there is a global improvement in behavior as assessed by the Clinical Global Impression of Improvement.
Global changes in behavior and will serve as an anchor to assess the meaningfulness of change. A lower score indicates a better outcome. A higher score indicates a worse outcome. The maximum score is 7. The minimum score is 1.
Measured: Change in the Clinical Global Impression of Improvement from baseline to months 3, 6, 9.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2023
- Study start8 Jan 2024
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prader-Willi SyndromeStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Foundation for Prader-Willi Research
- Sponsor type
- University, hospital or other
- Collaborators
- RTI International
- Responsible party
- Sponsor
- Investigators
- Theresa Strong, PhD, Principal investigator, Foundation for Prader-Willi ResearchDeepan Singh, MD, Principal investigator, Maimonides Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06144645
- Sponsor's protocol ID
- FPWR-VNS-R-3-01
- Acronym
- VNS4PWS
- Status last verified
- Apr 2026
- First submitted
- 16 Oct 2023
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06144645
- Acronym / sponsor ID
- VNS4PWS / FPWR-VNS-R-3-01
- Conditions
- Prader-Willi Syndrome
- Keywords
- Prader-Willi syndrome, PWS, Prader
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Foundation for Prader-Willi ResearchUniversity, hospital or other
- Collaborators
- RTI International
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 22 Nov 2023 (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.
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.
Detailed description
The main questions the VNS4PWS study seeks to answer are: (1) is tVNS treatment safe in people with PWS, (2) is tVNS treatment acceptable to people with PWS, and (3) is tVNS an effective treatment to reduce temper outbursts in people with PWS. Participants will wear the tVNS device daily for 4 hours over a period of 9 months. Two different doses of tVNS will be compared. During the final three months of the trial, the effect of stopping treatment will be studied. After the first year of the study, participants will have the opportunity to continue on to a 1-year open label extension period during which active tVNS treatment will be resumed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tVNS, Intermittent Stimulation | Active comparator | Device: tVNS, intermittent stimulation28 seconds on, 32 seconds off |
| tVNS, Continuous Stimulation | Active comparator | Device: tVNS, continuous stimulationcontinuous stimulation |
Who may qualify
- Ages
- 10 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
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 |
|---|---|---|
| tVNS, intermittent stimulationAlso: tVNS R, manufactured by tVNS Technologies, intermittent stimulationtranscutaneous vagus nerve stimulation, intermittent stimulation | Device | tVNS, Intermittent Stimulation |
| tVNS, continuous stimulationAlso: tVNS R, manufactured by tVNS Technologies, continuous stimulationtranscutaneous vagus nerve stimulation, continuous stimulation | Device | tVNS, Continuous Stimulation |
Primary outcome
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.
Time frame: Through study completion, an average of 1 year
Frequency, severity, and seriousness of adverse events during the study.
To determine the acceptability profile of tVNS in PWS as assessed by the rate of withdrawal from the study.
Time frame: Through study completion, an average of 1 year
The acceptability profile of tVNS in PWS will be measured by the rate of withdrawal from the study.
To determine the acceptability profile of tVNS in PWS as assessed by the rates of device use compliance during the study.
Time frame: Through study completion, an average of 1 year
The acceptability profile of tVNS in PWS will be measured by the rates of device use compliance throughout the study.
To determine the efficacy of tVNS in reducing temper outbursts in people with PWS aged 10 - 40 years.
Time frame: Baseline to month 9
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.
11 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to months 3, 6, 9, and 12.
To determine whether tVNS reduces the average duration of temper outbursts per day.
Time frame: 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.
Time frame: Baseline to months 3, 6, and 9.
To determine whether tVNS treatment decreases skin picking in PWS, as assessed by the Self Injury Trauma Scale.
Time frame: Baseline to months 3, 6, and 9.
To determine whether tVNS decreases anxiousness and distress in PWS as measured by the PWS Anxiousness and Distress Questionnaire.
Time frame: Change in PWS Anxiousness and Distress Questionnaire at baseline and months 3, 6, and 9.
To determine whether reductions in temper outbursts result in reduced caregiver burden as measured by the Zarit Burden Interview.
Time frame: Change in Zarit Burden Interview (ZBI) between baseline and month 9.
To determine whether reductions in temper outburst is associated with improved quality of life as measured by the Parent Proxy Global Health 7.
Time frame: Change in Parent Proxy Global Health 7 from baseline to months 3, 6, 9.
To assess whether overall disease severity is improved as measured by the Change in the Clinical Global Impression of disease severity.
Time frame: Change in the Clinical Global Impression of disease severity at baseline and months 3, 6, 9.
To assess whether there is a global improvement in behavior as assessed by the Clinical Global Impression of Improvement.
Time frame: Change in the Clinical Global Impression of Improvement from baseline to months 3, 6, 9.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- 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.
Theresa Strong, PhD principal investigator
Foundation for Prader-Willi Research
Deepan Singh, MD principal investigator
Maimonides Medical Center
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing tVNS, intermittent stimulation and tVNS, continuous stimulation in people with Prader-Willi Syndrome, run by Foundation for Prader-Willi Research at 18 sites in United States.
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 10 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
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. (time frame: Through study completion, an average of 1 year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Apr 2026.