Potential Benefit for Non Invasive Vagus Nerve Stimulation Using GammaCore in the Treatment of Raynaud's Phenomena.

June 25, 2025 updated by: Bashar Kahaleh, M.D, University of Toledo Health Science Campus

Potential Benefit for Non Invasive Vagus Nerve Stimulation (nVNS) Using GammaCore in the Treatment of Raynaud's Phenomena.

Raynaud's phenomenon (RP) is a common vascular disorder that affects approximately 10% of the general population. RP is associated with significant morbidity that may include loss of the digits due to repeated episodes of vasospasm of the digital arteries in addition to significant impairment of quality of life. It is well known that cold exposure precipitates episodes of RP, but the mechanism for cold sensitivity is not known, and treatment of RP is not satisfactory to the patients and their physicians.

The goal in this study is to test the possibility that non invasive vagus nerve stimulation (nVNS) with gammaCore which is already approved by the FDA for headaches and migraines may be an effective and well tolerated therapy for Raynaud's Phenomenon.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Raynaud's phenomenon (RP) is a common vascular disorder that that affects approximately 10% of the general population. RP causes some areas of the body (i.e. fingers and toes) to feel cold and numb in response to cold exposure or emotional stress. Raynaud's phenomenon is characterized by reversible vasospasm of the fingers and toes. This reversible narrowing of the small arteries induces episodes of color changes of the fingers and toes. During an attack of Raynaud's, affected areas of the skin usually first turn white, then they often turn blue and feel cold and numb (pins and needles). As the fingers warm and circulation improves the affected areas may turn red, throb and tingle.

Moreover, Raynaud's phenomenon can be associated with significant morbidity that may include ulceration of fingers and loss of the fingers and toes due to repeated episodes of reversible narrowing of arteries supplying blood to the finger and toes. It is well known that cold exposure leads to episodes of RP, but the mechanism for cold sensitivity is not known, and treatment of RP is not satisfactory to the patients and their physicians.

Raynaud's phenomenon is classified as Primary Raynaud's phenomenon (PRP) in the absence of other vascular or connective tissue disease. Raynaud's phenomenon is classified as Secondary Raynaud's phenomenon (SRP) if it is associated with connective tissue disease, like systemic sclerosis (SSc, Scleroderma).

Treatment of Raynaud's phenomenon is not satisfactory in general, as current therapy employing calcium channel blockers and other vasodilators are frequently ineffective or not well tolerated, due to significant side effects.

Noninvasive vagus nerve stimulation (nVNS) is currently FDA approved for therapeutic uses in patient ages 12 and above to treat cluster and migraine headaches. Recent studies have shown that vagal nerve stimulation has vasodilatory and anti-inflammatory properties which has led to more preclinical research examining vagus nerve stimulation as treatment for a wider range of inflammatory and autoimmune disorders. Vagus nerve stimulation has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis, and diabetes. Although there are no direct data to demonstrate vagus nerve stimulation's effect in Raynaud's phenomenon, the investigators believe that VNS's success in treating headache and migraine attacks indirectly support its use in Raynaud's phenomenon by its direct effect on vasospasms (narrowing of blood vessels). In fact migraine has been found as a risk factor for the development of Raynaud's phenomenon further supports this notion.

GammaCore is a safe and effective non-drug treatment approved for treating cluster and migraine headaches. It is a patented device that activates the vagus nerve with gentle electrical stimulation. The vagus nerve is an important highway of communication between the brain and many parts of the body, it plays an important role in regulating pain. Noninvasive vagus nerve stimulation with GammaCore is believed to help block the pain signals that cause migraines and cluster headaches. Unlike traditional vagus nerve stimulation therapies, gammaGore stimulates the vagus nerve through the skin at the side of the neck without the need for surgery. This non-invasive method avoids many side effects and inconveniences associated with injectable, inhaled or pill-based medication.

The investigators' goal is to test the possibility that noninvasive vagus nerve stimulation using gammaCore may be an effective and well tolerated therapy for Raynaud's phenomenon. The investigators aim to gain a fundamental understanding of the role of noninvasive vagus nerve stimulation as a potential therapy for Raynaud's phenomenon, a truly unmet medical need.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Toledo, Ohio, United States, 43614
        • Unversity of Toledo Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

• Clinical Diagnosis of Primary Raynaud's Phenomenon

Exclusion Criteria:

  • Less than 18 years of age
  • Pregnant women
  • Current smokers
  • Have Digital ulcers
  • Diagnosed Pulmonary hypertension
  • Currently on vasodilators (i.e. Phosphodiesterase type 5 inhibitors, prostacyclin, nitroglycerine, or other nitric oxide derivatives)
  • Currently on Calcium Channel Blockers

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Sham Device Group

15 patients will be randomized to the Sham device for the first half of the treatment window then switch to the gammaCore Sapphire device (study device) for the rest of the study.

The Sham device will look exactly like the gammaCore Sapphire device but will not deliver non invasive vagus nerve stimulation.
Device: gammaCore Sapphire

gammaCore SapphireTM (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore provides a mild electrical stimulation to the vagus nerve, which runs through the neck and carries information to the central nervous system.

Subjects will be instructed to use the gammaCore Sapphire to stimulate 2 minutes on each side of the neck, twice a day, every day. The subject controls the intensity level of the electrical stimulation.

Device: Sham Device
The Sham device delivers no electrical stimulations but subjects randomized to the Sham device will received the same instructions to use the Sham device to stimulate 2 minutes on each side of the neck, twice a day, every day for the first 4 weeks after randomization.
Experimental: gammaCore Sapphire (Study Device) Group
15 patients will be randomized to the gammaCore Sapphire device for the full length of the treatment window.
Device: gammaCore Sapphire

gammaCore SapphireTM (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore provides a mild electrical stimulation to the vagus nerve, which runs through the neck and carries information to the central nervous system.

Subjects will be instructed to use the gammaCore Sapphire to stimulate 2 minutes on each side of the neck, twice a day, every day. The subject controls the intensity level of the electrical stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Temperature in 4 Digits
Time Frame: Visit 1 which is Week -4 (Screening) to Visit 2 which is Week 0 (Randomization)
Temperature measured by infrared thermography
Visit 1 which is Week -4 (Screening) to Visit 2 which is Week 0 (Randomization)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Condition Scores
Time Frame: n/a - No data was collected.
The Raynaud's Condition Score is on a scale of 0 to 10 with "0" being no difficulty, "10" being extreme difficulty.
n/a - No data was collected.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rates
Time Frame: n/a - No data was collected. The transition from sham device to open label gammaCore nVNS device would not have occurred until Week +4. No subject reached Week 4 due to study being terminated prior to this visit.
Observe response rates in an open label fashion after subjects randomized to the sham device are transitioned to the gammaCore nVNS device.
n/a - No data was collected. The transition from sham device to open label gammaCore nVNS device would not have occurred until Week +4. No subject reached Week 4 due to study being terminated prior to this visit.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toledo Health Science Campus

Collaborators

ElectroCore INC

Investigators

  • Principal Investigator: Bashar Kahaleh, MD, University of Toledo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2019

Primary Completion (Actual)

February 27, 2020

Study Completion (Actual)

February 27, 2020

Study Registration Dates

First Submitted

February 20, 2019

First Submitted That Met QC Criteria

March 6, 2019

First Posted (Actual)

March 11, 2019

Study Record Updates

Last Update Posted (Actual)

July 15, 2025

Last Update Submitted That Met QC Criteria

June 25, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • gammaCore RP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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