Effects of Transcutaneous Vagus Nerve Stimulation on Emotion Regulation and Executive Functioning in Prader-Willi Syndrome

Official title

Auricular Vagal Neuromodulation Therapy (aVNT) for Enhancing Emotion Regulation, Executive Functions, Hyperphagia, and Quality of Life in Prader-Willi Syndrome: A Multicenter Randomized Controlled Trial

Overview

The STIM-PRADER study aims to assess the effectiveness of auricular vagal neuromodulation therapy (aVNT) on emotional, behavioral, and cognitive domains impaired in Prader-Willi Syndrome (PWS). Currently, no treatment exists that addresses the multiple alterations associated with this rare neurodevelopmental disorder that significantly impact patients and their families. We will investigate the effects of daily, four-hour aVNT stimulation over a nine-month period on (a) emotion regulation, including assessing the persistence of effects following stimulation; (b) executive functions, including inhibition, flexibility, planning, and updating information in memory; (c) hyperphagia; (d) depression; (e) quality of life; (e) and the threshold at which effects on these dimensions can be observed. We will conduct a longitudinal multicenter parallel randomized controlled single-blind exploratory trial. Twenty-four adults with PWS and 24 caregivers will be randomly assigned to receive either active or sham stimulation under identical conditions (four hours per day, seven days per week over nine months). The primary outcome, focusing on emotional control, will be assessed every two weeks for both participants and caregivers. Secondary outcomes (executive functions, hyperphagia, depression, and quality of life) will be measured at four time points: pre-intervention, at three months, six months, and at nine months. As this is the first multicenter randomized controlled trial investigating the effects of aVNT as a treatment in PWS patients, we anticipate witnessing improved emotional regulation and reduced eating disorders, along with enhancements in executive functions and quality of life in the active stimulation group. The findings from this project could support the development of broader therapeutic approaches for other conditions in which behavioral disorders and emotional processing deficits affect patients and their caregivers.

Interventions

• Device Auricular vagal neuromodulation therapy (aVNT)
  The aVNT device used in our study (Parasym ®) consists of a small portable unit connected to stimulation electrodes placed on the left ear. These electrodes deliver painless electrical microcurrents through the skin to stimulate the auricular branch of the vagus nerve (ABVN). The device parameters will be defined in accordance with the recommendations for use of the Parasym ® device and the pilot studies: frequency of 25 Hz, pulse width of 250 µS, and an intensity of 1 mA to 36 mA. Stimulation s
• Device Sham Auricular vagal neuromodulation therapy (aVNT)
  The sham stimulation control condition will be performed using the same aVNT Parasym® device under similar conditions (four hours a day, seven days a week, for nine months) but with a different location (without afferent vagus nerve fibers) or a control condition integrated into the device.

Primary outcome measures

• Evaluation of emotional control and regulation [Time frame: Every 2 weeks for 11 months (including 3 times before and post-stimulation)]

Secondary outcome measures (5)

• Evaluation of Behavioral manifestations of executive functioning [Time frame: 4 times (at 0, 3, 6 and 9 months)]
• Evaluation of Executive functions [Time frame: 4 times (at 0, 3, 6 and 9 months)]
• Evaluation of Hyperphagia [Time frame: 4 times (at 0, 3, 6 and 9 months)]
• Evaluation of Depression [Time frame: 4 times (at 0, 3, 6 and 9 months)]
• Evaluation of Quality of life [Time frame: 4 times (at 0, 3, 6 and 9 months)]

Eligibility criteria

Inclusion criteria

• Participant with PWS: Age : ≥ 18 years old; Diagnosis of Prader-Willi syndrome with identified genotype; Intellectual Quotient ≥ 55 measured by WAIS-IV (abbreviated version); Pathological or threshold score on at least one of the BRIEF-A subscales; Adults volunteering and able to comply with study procedures; Signature of informed consent form; Beneficiary of a social security regime
• Caregivers: Caregivers involved in the participant's family, medical or institutional environment; Caregiver who has signed the informed consent form.

Exclusion criteria

• Participant with PWS: Untreated and unstabilized psychiatric and/or behavioral disorders (psychological decompensation within the last year); Severe visual or hearing impairment; Untreated sleep apnea syndrome; Epileptic seizures; Previous significative ECG abnormality; Adults with pacemakers or defibrillators; Metal or electronic devices implanted in the head; Participation in other research involving an exclusion period still in progress at inclusion; Score ≥ 30 indicating severe depression (BDI-II self-report questionnaire); Pregnant or breast-feeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

France · 4 centers

• Reference Center of Prader-Willi Syndrome (PRADORT) — Bordeaux
• Reference Center of Prader-Willi Syndrome (CRMR PRADORT) — Hendaye
• Reference Center of Prader-Willi Syndrome (PRADORT) — Paris
• Reference Center of Prader-Willi Syndrome (PRADORT) — Toulouse

Identifiers

NCT: NCT06720571 · 2023-A00915-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗