Vagus Nerve Stimulation for PWS

(VNS4PWS Trial)

Recruiting at 18 trial locations

Overseen By Lisa Matesevac, AuD

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Foundation for Prader-Willi Research

Disqualifiers: Pregnancy, Serious mental illness, Cardiac disease, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment method called transcutaneous vagus nerve stimulation (tVNS) for individuals with Prader-Willi Syndrome (PWS). The researchers aim to determine if tVNS is effective, safe, and acceptable for managing PWS symptoms, with a focus on reducing temper outbursts. Participants will receive either continuous or intermittent stimulation to compare the effects. Suitable candidates have a confirmed PWS diagnosis and experience at least two temper outbursts per week. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

You can continue taking your current psychiatric medications as long as you have been on a stable dose for 90 days before the study and do not plan to change the dose during the study.

What prior data suggests that transcutaneous vagus nerve stimulation (tVNS) is safe for people with PWS?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) is generally safe. One study examined its safety and found it both safe and practical. In another study, tVNS helped people with Prader-Willi Syndrome (PWS) without major safety issues, and it reduced temper outbursts.

These findings are promising for those considering joining a clinical trial. They suggest that tVNS is well-tolerated, with no serious side effects reported, providing reassurance for participants considering this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about transcutaneous Vagus Nerve Stimulation (tVNS) for Prader-Willi Syndrome (PWS) because it offers a non-invasive approach to managing symptoms by directly stimulating the vagus nerve. Unlike current treatments that often involve medication to manage behavioral or hormonal issues, tVNS uses electrical impulses to potentially influence brain activity and improve symptoms. This method is unique in its delivery, providing continuous or intermittent stimulation options to tailor the treatment to individual needs. By potentially modulating neural pathways without medication, tVNS could offer a novel and less intrusive alternative for people with PWS.

What evidence suggests that tVNS is effective for PWS?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) might help people with Prader-Willi Syndrome (PWS) by improving behavior and emotional control. This trial will compare two approaches to tVNS: continuous and intermittent stimulation. Studies have found that tVNS can reduce problem behaviors in individuals with neurodevelopmental disorders, including PWS. Some research suggests that tVNS can help regulate heart rate patterns by affecting the part of the nervous system that controls automatic body functions. Additionally, tVNS is considered a safe way to manage frequent temper outbursts in people with PWS, possibly by influencing brain pathways. These findings suggest that tVNS could effectively improve the quality of life for those with PWS. ^{2 4 6 7 8}

Who Is on the Research Team?

Deepan Singh, MD

Principal Investigator

Maimonides Medical Center

Theresa Strong, PhD

Principal Investigator

Foundation for Prader-Willi Research

Are You a Good Fit for This Trial?

This trial is for individuals aged 10-40 with Prader-Willi Syndrome (PWS) who have had at least two temper outbursts per week in the past six months. Participants must be on a stable dose of psychiatric medication and therapy regimen for three months prior, willing to share data, and have internet access. Caregivers must support data collection.

Inclusion Criteria

I've been on a stable dose of psychiatric medication for 90 days with no changes planned.

I've been on a stable mental health treatment plan for 90 days with no changes expected.

I agree to share my treatment app data and daily mood changes with the study team.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tVNS treatment daily for 4 hours over a period of 9 months, comparing two different doses.

9 months

Withdrawal

The effect of stopping treatment is studied during the final three months of the trial.

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

Open-label extension

Participants have the opportunity to continue on to a 1-year open label extension period with active tVNS treatment.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• tVNS

Trial Overview The study examines transcutaneous vagus nerve stimulation (tVNS) as a treatment for PWS-related temper outbursts. It will compare continuous versus intermittent tVNS to see which is more effective, safe, and acceptable.

How Is the Trial Designed?

Group I: tVNS, Continuous Stimulation Active Control 1 Intervention

continuous stimulation

Group II: tVNS, Intermittent Stimulation Active Control 1 Intervention

28 seconds on, 32 seconds off

tVNS is already approved in European Union, United States for the following indications:

Approved in European Union as Transcutaneous Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Chronic pain
• Migraines

Approved in United States as Transcutaneous Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Chronic pain

Who Is Running the Clinical Trial?

Foundation for Prader-Willi Research

Lead Sponsor

Trials

14

Recruited

1,200+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Published Research Related to This Trial

Transcutaneous vagus nerve stimulation (tVNS) is a promising non-invasive alternative to traditional vagus nerve stimulation (VNS) for treating conditions like epilepsy and depression, which can be invasive and have side effects.

There is ongoing research into the best stimulation parameters and sites for tVNS, particularly focusing on stimulation at the outer ear, to optimize its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas. Hilz, MJ., Bolz, A.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced postural tachycardia in patients with POTS, showing a mean heart rate increase of 17.6 beats/min in the active group compared to 31.7 beats/min in the sham group after 2 months.

tVNS also led to lower levels of antiadrenergic autoantibodies and inflammatory cytokines, along with improved heart rate variability, indicating its potential as a safe and effective noninvasive treatment for POTS without any reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. Stavrakis, S., Chakraborty, P., Farhat, K., et al.[2023]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) showed promising results in two patients with structural focal epilepsy, leading to seizure freedom in one patient after 4 weeks and significant reduction in seizures for the other after 20 weeks.

Both patients experienced improved quality of life with no significant adverse events reported, suggesting that taVNS could be a safe and effective treatment option for individuals with focal epilepsy and preserved cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. Shiraishi, H., Egawa, K., Murakami, K., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39405838/

Effects of long-term transcutaneous auricular vagus nerve ... The results suggest that taVNS may be effective by targeting ANS activity in individuals with PWS, contributing to improvements in behavioral regulation.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0891422224001872

Effects of long-term transcutaneous auricular vagus nerve ... Vagus nerve stimulation resulted in changes in circadian heart rate variability in Prader-Willi Syndrome. •. Rhythm-adjusted mean heart rate variability ...

3. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0223750

Transcutaneous vagus nerve stimulation (t-VNS) Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06720571?term=AREA%5BConditionSearch%5D(%22Prader-Willi%20syndrome%22)&rank=4

Effects of Transcutaneous Vagus Nerve Stimulation on ... The STIM-PRADER study aims to assess the effectiveness of auricular vagal neuromodulation therapy (aVNT) on emotional, behavioral, and cognitive domains ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31794560/

Transcutaneous vagus nerve stimulation (t-VNS): A novel ... t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772204/

Safety of transcutaneous auricular vagus nerve stimulation ... This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06720571?cond=%22Prader-Willi%20Syndrome%22&aggFilters=status:not%20rec&rank=3

Effects of Transcutaneous Vagus Nerve Stimulation on ... The STIM-PRADER study aims to assess the effectiveness of auricular vagal neuromodulation therapy (aVNT) on emotional, behavioral, and cognitive domains ...

8. fpwr.org fpwr.org/blog/exciting-new-treatment-may-reduce-disruptive-behaviors-in-pws

Exciting New Treatment May Reduce Disruptive Behaviors ... Recent evidence from FPWR-supported studies shows that Vagus Nerve Stimulation (VNS) may reduce temper outbursts and other disruptive behaviors in individuals ...