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

NCT03869008 | Terminated Results FDA Device

• 1 other identifier: gammaCore RP
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Raynaud Phenomenon; Primary Raynaud Phenomenon; Raynaud Disease; Raynaud Syndrome

Outcome Measures

Primary Outcomes (1)

• Temperature in 4 Digits

  Temperature measured by infrared thermography

  Visit 1 which is Week -4 (Screening) to Visit 2 which is Week 0 (Randomization)

Secondary Outcomes (1)

• Condition Scores

  n/a - No data was collected.

Other Outcomes (1)

• Response Rates

  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.

Study Arms (2)

Sham Device Group

SHAM COMPARATOR

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; Device: Sham Device

gammaCore Sapphire (Study Device) Group

EXPERIMENTAL

15 patients will be randomized to the gammaCore Sapphire device for the full length of the treatment window.

Device: gammaCore Sapphire

Interventions

gammaCore Sapphire DEVICE

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.

Sham Device Group; gammaCore Sapphire (Study Device) Group

Sham Device 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.

Sham Device Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical Diagnosis of Primary Raynaud's Phenomenon

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Toledo Health Science Campus: lead
• ElectroCore INC: collaborator

Study Sites (1)

Unversity of Toledo Medical Center

Toledo, Ohio, 43614, United States

Location

Related Publications (13)

• Garner R, Kumari R, Lanyon P, Doherty M, Zhang W. Prevalence, risk factors and associations of primary Raynaud's phenomenon: systematic review and meta-analysis of observational studies. BMJ Open. 2015 Mar 16;5(3):e006389. doi: 10.1136/bmjopen-2014-006389.

  PMID: 25776043 BACKGROUND

• Brand FN, Larson MG, Kannel WB, McGuirk JM. The occurrence of Raynaud's phenomenon in a general population: the Framingham Study. Vasc Med. 1997 Nov;2(4):296-301. doi: 10.1177/1358863X9700200404.

  PMID: 9575602 BACKGROUND

• Merkel PA, Herlyn K, Martin RW, Anderson JJ, Mayes MD, Bell P, Korn JH, Simms RW, Csuka ME, Medsger TA Jr, Rothfield NF, Ellman MH, Collier DH, Weinstein A, Furst DE, Jimenez SA, White B, Seibold JR, Wigley FM; Scleroderma Clinical Trials Consortium. Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon. Arthritis Rheum. 2002 Sep;46(9):2410-20. doi: 10.1002/art.10486.

  PMID: 12355489 BACKGROUND

• Matucci-Cerinic M, Kahaleh B, Wigley FM. Review: evidence that systemic sclerosis is a vascular disease. Arthritis Rheum. 2013 Aug;65(8):1953-62. doi: 10.1002/art.37988. No abstract available.

  PMID: 23666787 BACKGROUND

• Ennis H, Anderson ME, Wilkinson J, Herrick AL. Calcium channel blockers for primary Raynaud's phenomenon. Cochrane Database Syst Rev. 2014 Jan 30;(1):CD002069. doi: 10.1002/14651858.CD002069.pub4.

  PMID: 24482037 BACKGROUND

• Coleiro B, Marshall SE, Denton CP, Howell K, Blann A, Welsh KI, Black CM. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology (Oxford). 2001 Sep;40(9):1038-43. doi: 10.1093/rheumatology/40.9.1038.

  PMID: 11561116 BACKGROUND

• Pauling JD, Shipley JA, Harris ND, McHugh NJ. Use of infrared thermography as an endpoint in therapeutic trials of Raynaud's phenomenon and systemic sclerosis. Clin Exp Rheumatol. 2012 Mar-Apr;30(2 Suppl 71):S103-15. Epub 2012 May 30.

  PMID: 22691218 BACKGROUND

• James PB. Cooling patterns in Raynaud's phenomenon and allied peripheral vascular disorders. Br J Surg. 1968 Nov;55(11):860. No abstract available.

  PMID: 5686991 BACKGROUND

• Zaproudina N, Varmavuo V, Airaksinen O, Narhi M. Reproducibility of infrared thermography measurements in healthy individuals. Physiol Meas. 2008 Apr;29(4):515-24. doi: 10.1088/0967-3334/29/4/007. Epub 2008 Apr 9.

  PMID: 18401069 BACKGROUND

• Pauling JD, Shipley JA, Raper S, Watson ML, Ward SG, Harris ND, McHugh NJ. Comparison of infrared thermography and laser speckle contrast imaging for the dynamic assessment of digital microvascular function. Microvasc Res. 2012 Mar;83(2):162-7. doi: 10.1016/j.mvr.2011.06.012. Epub 2011 Jul 1.

  PMID: 21763703 BACKGROUND

• Schlager O, Gschwandtner ME, Herberg K, Frohner T, Schillinger M, Koppensteiner R, Mlekusch W. Correlation of infrared thermography and skin perfusion in Raynaud patients and in healthy controls. Microvasc Res. 2010 Jul;80(1):54-7. doi: 10.1016/j.mvr.2010.01.010. Epub 2010 Feb 6.

  PMID: 20144625 BACKGROUND

• Johnson RL, Wilson CG. A review of vagus nerve stimulation as a therapeutic intervention. J Inflamm Res. 2018 May 16;11:203-213. doi: 10.2147/JIR.S163248. eCollection 2018.

  PMID: 29844694 BACKGROUND

• Silberstein SD, Calhoun AH, Treppendahl C, Dodick DW, Rapoport AM, Mamidi A, Vargas P, Ebert TH, Tepper SJ. The emerging role of gammaCore(R) in the management of cluster headache: expert panel recommendations. Am J Manag Care. 2017 Nov;23(17 Suppl):S326-S333.

  PMID: 29144718 BACKGROUND

Related Links

• Safety information on the gammaCore Sapphire device.

MeSH Terms

Conditions

Raynaud Disease

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Bashar Kahaleh, MD
• Organization: UTMC

bashar.kahaleh@utoledo.edu

4193834271

Study Officials

• Bashar Kahaleh, MD

  University of Toledo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: March 11, 2019
• Study Start: April 30, 2019
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: July 15, 2025
• Results First Posted: July 15, 2025

Record last verified: 2025-05

Locations

US (1)