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)
概览
- 阶段
- 3 期
- 干预措施
- tVNS, intermittent stimulation
- 疾病 / 适应症
- Prader-Willi Syndrome
- 发起方
- Foundation for Prader-Willi Research
- 入组人数
- 102
- 试验地点
- 35
- 主要终点
- 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.
- 状态
- 进行中（未招募）
- 最后更新
- 26天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
tVNS, Intermittent Stimulation
28 seconds on, 32 seconds off
干预措施: tVNS, intermittent stimulation
tVNS, Continuous Stimulation
continuous stimulation
干预措施: tVNS, continuous stimulation
结局指标
主要结局
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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
次要结局
- To determine whether tVNS treatment decreases skin picking in PWS, as assessed by the Self Injury Trauma Scale.(Baseline to months 3, 6, and 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.(Baseline to months 3, 6, 9.)
- 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 decreases anxiousness and distress in PWS as measured by the PWS Anxiousness and Distress Questionnaire.(Change in PWS Anxiousness and Distress Questionnaire at baseline and months 3, 6, and 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 decreases PWS-associated hyperphagic behaviors as measured by the Hyperphagia Questionnaire for Clinical Trials.(Baseline to months 3, 6, and 9.)
- To determine whether tVNS reduces the average duration of temper outbursts per day.(Baseline to months 3, 6, 9, and 12.)
- To determine whether reductions in temper outbursts result in reduced caregiver burden as measured by the Zarit Burden Interview.(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.(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.(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.(Change in the Clinical Global Impression of Improvement from baseline to months 3, 6, 9.)