Safety and Efficacy Vagal Nerve Stimulation in Patients With Rheumatoid Arthritis

Pilot Study of the Safety and Efficacy of Neurostimulation of the Cholinergic Anti-Inflammatory Pathway Using an Active Implantable Vagal Nerve Stimulation Device in Patients With Rheumatoid Arthritis

This is a 12 week open label pilot study to determine the efficacy and safety of a surgically implanted, electrically active vagal nerve stimulation device in patients with active rheumatoid arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Device: Cyberonics VNS System

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Mostar, Bosnia and Herzegovina
    • Sveučilišna klinička bolnica Mostar
  • Sarajevo, Bosnia and Herzegovina
    • Klinicki Centar Univerziteta, Reumatologija
• Croatia
  • Zagreb, Croatia
    • Sisters of Mercy Clinical Hospital Centre
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center, University of Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult-onset rheumatoid arthritis of at least six months duration as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010)
• Male or female patients, 18-75 years of age, inclusive
• Functional status I, II, or III as classified according to the ACR 1991 revised criteria (Hochberg, 1992)
• Patients must have active disease as defined by at least 4 active tender or swollen joints and CRP above 0.7 mg/dL, despite at least 3 months of treatment with methotrexate at a dose of up to 25 mg orally per week.
• Patients may have been previously treated with TNF antagonists, but must have failed by reason of inadequate safety, intolerance to side effects, or development of antibodies (i.e., secondary failures), and specifically cannot have failed on the basis of primary lack of efficacy
• Study amended to add a second cohort of up to 10 patients who have failed both a TNF antagonist and at least one other biological therapy having a non-TNF antagonist mechanism of action

Exclusion Criteria:

• History of unilateral or bilateral vagotomy
• History of recurrent vaso-vagal syncope episodes
• Known obstructive sleep apnea
• Known history of cardiac rhythm disturbances, atrio-ventricular block of greater than first degree, or cardiac conduction pathway abnormalities other than isolated right bundle branch block or isolated left anterior fascicle block
• Significant pharyngeal dysfunction or swallowing difficulties
• Pre-existing clinically significant vocal cord damage or hoarseness
• Previously implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators)
• Asthma or chronic obstructive pulmonary disease not controlled by medications, or any other disease causing clinically significant dyspnea at time of screening
• Active peptic ulcer disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vagal Nerve Stimulation	Device: Cyberonics VNS System; Active Implantable Electrical Vagal Nerve Stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in DAS from baseline	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with ACR 20 response	6 weeks

Collaborators and Investigators

• Sponsor: SetPoint Medical Corporation
• Investigators: Principal Investigator: Paul-Peter Tak, M.D., Ph.D., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: March 8, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (Estimate): March 13, 2012

Study Record Updates

• Last Update Posted (Estimate): November 1, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Vagus Nerve; Vagal Nerve Stimulation; Implantable Medical Device
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: SPM-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No