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

NCT06720571 | Recruiting

• 1 other identifier: 2023-A00915-40
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prader-Willi Syndrome

Keywords

Prader-Willi Syndrome; Vagus nerve stimulation; aVNT; t-VNS; Cognition; Executive functions; Inhibition; Flexibility; Planning; Updating; Emotion regulation; Behavior; Hyperphagia; Quality of life; Depression; Multicenter randomized controlled trial; Caregivers

Outcome Measures

Primary Outcomes (1)

• Evaluation of emotional control and regulation

  The primary outcome measure will focus on assessing emotional control (EC) through a subscale of the BRIEF-A (Behavior Inventory Related to Executive Functions - Adult version).

  Every 2 weeks for 11 months (including 3 times before and post-stimulation)

Secondary Outcomes (5)

• Evaluation of Behavioral manifestations of executive functioning

  4 times (at 0, 3, 6 and 9 months)

• Evaluation of Executive functions

  4 times (at 0, 3, 6 and 9 months)

• Evaluation of Hyperphagia

  4 times (at 0, 3, 6 and 9 months)

• Evaluation of Depression

  4 times (at 0, 3, 6 and 9 months)

• Evaluation of Quality of life

  4 times (at 0, 3, 6 and 9 months)

Study Arms (2)

Active stimulation

EXPERIMENTAL

Device: Auricular vagal neuromodulation therapy (aVNT)

Sham stimulation

SHAM COMPARATOR

Device: Sham Auricular vagal neuromodulation therapy (aVNT)

Interventions

Auricular vagal neuromodulation therapy (aVNT) DEVICE

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 sessions will last for four hours each day, each of which can be divided into two sessions and conducted over a period of nine months. Patients will adjust the intensity at each session according to their comfort level, starting with a gradual increase until they feel a slight tingling sensation, followed by a decrease until discomfort disappears completely. Stimulation should take place during a relaxing activity but not should not take place during sleep, meals or major physical activity.

Active stimulation

Sham Auricular vagal neuromodulation therapy (aVNT) DEVICE

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.

Sham stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• University of Bordeaux: lead
• John Bost Foundation: collaborator
• University Hospital, Bordeaux: collaborator
• Hendaye hospital: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• University Hospital, Toulouse: collaborator
• Prader-Willi Syndrome Association: collaborator

Study Sites (4)

Reference Center of Prader-Willi Syndrome (PRADORT)

Bordeaux, 33600, France

NOT YET RECRUITING

Reference Center of Prader-Willi Syndrome (CRMR PRADORT)

Hendaye, 64700, France

RECRUITING

Reference Center of Prader-Willi Syndrome (PRADORT)

Paris, 75013, France

RECRUITING

Reference Center of Prader-Willi Syndrome (PRADORT)

Toulouse, 31000, France

RECRUITING

MeSH Terms

Conditions

Prader-Willi Syndrome; Inhibition, Psychological; Emotional Regulation; Behavior; Hyperphagia; Depression

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Self-Control; Social Behavior; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms

Study Officials

• Virginie Postal, PhD

  University of Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Virginie Postal, PhD

CONTACT

+33 (0)57 57 19 74; virginie.postal@u-bordeaux.fr

Camille Nahon, PhD student, neuropsychologist

CONTACT

+33 05 57 57 19 64; camille.nahon@u-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher and Professor

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 6, 2024
• Study Start: November 22, 2023
• Primary Completion: March 30, 2026
• Study Completion: March 30, 2026
• Last Updated: December 6, 2024

Record last verified: 2024-12

Locations

FR (4)