A Phase 3 interventional study of tVNS, intermittent stimulation and tVNS, continuous stimulation in Prader-Willi Syndrome, sponsored by Foundation for Prader-Willi Research. Active, not recruiting at 18 sites in United States. Open to participants aged 10 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-04-06.
Sponsored by Foundation for Prader-Willi Research · Phase 3, Interventional, and Treatment
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.
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.
138 studies on the registry are indexed under Prader-Willi Syndrome; 24 are open to participants now.
This study's planned enrollment of 102 is above the median of 30 across 96 interventional studies indexed under Prader-Willi Syndrome.
Browse Prader-Willi Syndrome studies →Foundation for Prader-Willi Research is the lead sponsor of 3 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
28 seconds on, 32 seconds off
Device: tVNS, intermittent stimulation
continuous stimulation
Device: tVNS, continuous stimulation
transcutaneous vagus nerve stimulation, intermittent stimulation
Also known as: tVNS R, manufactured by tVNS Technologies, intermittent stimulation
transcutaneous vagus nerve stimulation, continuous stimulation
Also known as: tVNS R, manufactured by tVNS Technologies, continuous stimulation
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to month 9
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.
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.
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.
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.
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.
Time frame: 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Time frame: Change in the Clinical Global Impression of Improvement from baseline to months 3, 6, 9.
Informant and self-reported measures of acceptability as assessed by a qualitative exit interview.
To qualitatively determine the acceptability of tVNS in people with PWS and to better understand specific reasons for discontinuation that occurred in this study.
Time frame: Through study completion, an average of 1 year.
Identification of responder characteristics as identified in a qualitative exit interview.
Participant characteristics and information provided in semi-structured exit interviews will inform efforts to identify those most likely to benefit from this intervention.
Time frame: Through study completion, an average of 1 year.
To assess the change heart rate variability (HRV) in a subset of participants.
Heart rate variability is abnormal in PWS, and VNS may cause changes in HRV.
Time frame: Through study completion, an average of 1 year.
Plan to share: No
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This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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Foundation for Prader-Willi Research