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

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ClinicalTrials.gov Identifier: NCT03869008
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : March 11, 2019
Sponsor:
Collaborator:
ElectroCore INC
Information provided by (Responsible Party):
Bashar Kahaleh, M.D, University of Toledo Health Science Campus

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Raynaud Phenomenon Primary Raynaud Phenomenon Raynaud Disease Raynaud Syndrome Device: gammaCore Sapphire Device: Sham Device Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

At randomization subjects are randomized to 2 groups, the Experimental group and the Sham group.

The Experimental group will use the study device from randomization to the end of the study.

The Sham group will use the Sham device for 4 weeks after randomization then be switched to the study device for the rest of the study.

Masking: Single (Participant)
Masking Description:

Subjects randomized to the Experimental group will use the gammaCore Sapphire till the end of the study. Subjects in this group will become un-blinded in the open label phase of the study at 4 weeks after randomization.

Subjects randomized to the Sham group will use the Sham device for 4 weeks. Subjects in the Sham group will become un-blinded in the open label phase of the study at 4 weeks after randomization and be switch to the gammaCore Sapphire for the rest of the study.

Primary Purpose: Treatment
Official Title: Potential Benefit for Non Invasive Vagus Nerve Stimulation (nVNS) Using GammaCore in the Treatment of Raynaud's Phenomena.
Estimated Study Start Date : March 15, 2019
Estimated Primary Completion Date : January 16, 2020
Estimated Study Completion Date : March 16, 2020

Resource links provided by the National Library of Medicine


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.





Primary Outcome Measures :
  1. Evaluate the clinical efficacy of the gammaCore nVNS device at preventing vasospasms, thus reducing the number of and duration of Raynaud's attacks in patients with Primary Raynaud's Phenomenon. [ Time Frame: 12 weeks ]

    Evaluate the clinical efficacy of gammaCore (15 patients) vs sham device (15 patients) in preventing vasospasms in 30 PRP patients.

    The clinical efficacy of the nVNS device will be accessed through subject reported outcomes by way of the diary that will be handed out to subjects for the duration of the study, both before and after subjects have started using the gammaCore device. The diary will track daily the number of attacks of Raynaud's phenomenon and the duration of these attacks each day. The combination of the number of RP attacks and their duration will be used to evaluate the efficacy of the nVNS device at preventing vasospasms by analyzing changes in frequency and duration of RP attacks in subjects before and after they have started using the gammaCore device.



Secondary Outcome Measures :
  1. Evaluate improvements in Raynaud's condition scores after using the gammaCore nVNS device. [ Time Frame: 12 weeks ]

    Evaluate the clinical efficacy of gammaCore (15 patients) vs sham device (15 patients) on Raynaud's symptoms and chronic PRP in 30 patients for four weeks using Raynaud's condition score.

    The Raynaud's Condition Score is presented in the diary that will be handed out to subjects for the duration of the study. The Raynaud's Condition Score will ask subjects from a scale of 0 to 10, "0" being no difficulty, "10" being extreme difficulty, the number that best indicates the difficulty the subjects had each day with Raynaud's condition.

    The Raynaud's Condition Score is for subjects to rate how much difficulty the subjects had with Raynaud's each day by considering how much pain, numbness or other symptoms the Raynaud's caused in subjects' fingers and how much Raynaud's alone affected the use of the subjects' hands each day



Other Outcome Measures:
  1. Response rates [ Time Frame: 12 weeks ]
    Observe response rates in an open label fashion after subjects randomized to the sham device are transitioned to the gammaCore nVNS device.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03869008


Contacts
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Contact: Jennifer Gilmore, BSN 4193836761 jennifer.gilmore@utoledo.edu

Locations
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United States, Ohio
Unversity of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Jennifer Gilmore, BSN    419-383-6761    jennifer.gilmore@utoledo.edu   
Sponsors and Collaborators
University of Toledo Health Science Campus
ElectroCore INC
Investigators
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Principal Investigator: Bashar Kahaleh, MD University of Toledo

Additional Information:
Publications:

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Responsible Party: Bashar Kahaleh, M.D, Professor of Medicine, University of Toledo Health Science Campus
ClinicalTrials.gov Identifier: NCT03869008     History of Changes
Other Study ID Numbers: gammaCore RP
First Posted: March 11, 2019    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Raynaud Disease
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases