Clinical trial NCT06144645: A Clinical Evaluation of Non-Invasive Vagus Nerve Stimulation for Temper Outbursts in People With PWS
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Prader-Willi Syndrome
Keywords: Prader-Willi syndrome
PWS
Prader
Lead sponsor: Foundation for Prader-Willi Research
Sponsor class: OTHER
Collaborators: name: RTI International
First posted: 2023-11-22
Enrollment: 102
Sex: ALL
Minimum age (years): 10
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Genetically proven diagnosis of PWS.
2. Age 10-40 years.
3. History in the last six months of an average of at least two temper outbursts per week.
4. 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.
5. 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.
6. 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.
7. Living with family or in another setting with family members or staff willing to support the participant and the required data collection.
8. Agree to share tVNS patient application compliance and daily temper outburst data with the sponsor.
9. Access to cellular data or Wi-Fi.
10. Participant and caregiver speak American English as first language or are fluent in American English.

Exclusion Criteria:

1. Positive pregnancy test at screening, baseline, or at any point in the study.
2. Evidence of active or recent unstable serious mental illness, including, psychosis, mania, severe depression, or suicidality.
3. Moved to present residential placement in last three months or less.
4. Likely move in residential placement during the course of the study.
5. 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).
6. Evidence of clinically significant abnormalities of blood, liver, or kidney function from clinical safety laboratory assessments as determined by the Site Investigator.
7. History of blood clot, pulmonary embolism, or deep vein thrombosis.
8. Prior diagnosis of epilepsy or currently active seizures.
9. Current enrollment in the active phase of different clinical trial or interventional study.
10. 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.
11. Presence of dermal abnormalities at the stimulation site that would interfere with the ability of the tVNS device to function properly.
12. 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).
13. Severe, untreated sleep apnea, as self-reported by subject or caregiver or suspected by Site Investigator.
14. Subject is, in the opinion of the Investigator, not suitable to participate in the study.

Primary outcomes:
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.
timeFrame: Through study completion, an average of 1 year
measure: To determine the acceptability profile of tVNS in PWS as assessed by the rate of withdrawal from the study.
timeFrame: Through study completion, an average of 1 year
measure: To determine the acceptability profile of tVNS in PWS as assessed by the rates of device use compliance during the study.
timeFrame: Through study completion, an average of 1 year
measure: To determine the efficacy of tVNS in reducing temper outbursts in people with PWS aged 10 - 40 years.
timeFrame: Baseline to month 9
Secondary outcomes:
measure: 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.
timeFrame: Baseline to months 3, 6, 9.
measure: To determine whether tVNS reduces the average number of temper outbursts per day, as assessed by the Daily Survey.
timeFrame: Baseline to months 3, 6, 9, and 12.
measure: To determine whether tVNS reduces the average intensity of daily temper outbursts as measured by the Daily Survey.
timeFrame: Baseline to months 3, 6, 9, and 12.
measure: To determine whether tVNS reduces the average duration of temper outbursts per day.
timeFrame: Baseline to months 3, 6, 9, and 12.
measure: To determine whether tVNS decreases PWS-associated hyperphagic behaviors as measured by the Hyperphagia Questionnaire for Clinical Trials.
timeFrame: Baseline to months 3, 6, and 9.
measure: To determine whether tVNS treatment decreases skin picking in PWS, as assessed by the Self Injury Trauma Scale.
timeFrame: Baseline to months 3, 6, and 9.
measure: To determine whether tVNS decreases anxiousness and distress in PWS as measured by the PWS Anxiousness and Distress Questionnaire.
timeFrame: Change in PWS Anxiousness and Distress Questionnaire at baseline and months 3, 6, and 9.
measure: To determine whether reductions in temper outbursts result in reduced caregiver burden as measured by the Zarit Burden Interview.
timeFrame: Change in Zarit Burden Interview (ZBI) between baseline and month 9.
measure: To determine whether reductions in temper outburst is associated with improved quality of life as measured by the Parent Proxy Global Health 7.
timeFrame: Change in Parent Proxy Global Health 7 from baseline to months 3, 6, 9.
measure: To assess whether overall disease severity is improved as measured by the Change in the Clinical Global Impression of disease severity.
timeFrame: Change in the Clinical Global Impression of disease severity at baseline and months 3, 6, 9.
measure: To assess whether there is a global improvement in behavior as assessed by the Clinical Global Impression of Improvement.
timeFrame: Change in the Clinical Global Impression of Improvement from baseline to months 3, 6, 9.
Other outcomes:
measure: Informant and self-reported measures of acceptability as assessed by a qualitative exit interview.
timeFrame: Through study completion, an average of 1 year.
measure: Identification of responder characteristics as identified in a qualitative exit interview.
timeFrame: Through study completion, an average of 1 year.
measure: To assess the change heart rate variability (HRV) in a subset of participants.
timeFrame: Through study completion, an average of 1 year.
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center and Albert Einstein College of Medicine
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Garden City
country: United States
facility: NYU Langone Health
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: Christus Children'S
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Foundation for Prader-Willi Research
name: Theresa Strong, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maimonides Medical Center
name: Deepan Singh, MD
role: PRINCIPAL_INVESTIGATOR
References: