Clinical trial NCT01552941: Safety and Efficacy Vagal Nerve Stimulation in Patients With Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Keywords: Vagus Nerve
Vagal Nerve Stimulation
Rheumatoid Arthritis
Implantable Medical Device
Lead sponsor: SetPoint Medical Corporation
Sponsor class: INDUSTRY
First posted: 2012-03-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in DAS from baseline
timeFrame: 6 weeks
Secondary outcomes:
measure: Number of patients with ACR 20 response
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Mostar
country: Bosnia and Herzegovina
facility: Sveučilišna klinička bolnica Mostar
city: Sarajevo
country: Bosnia and Herzegovina
facility: Klinicki Centar Univerziteta, Reumatologija
city: Zagreb
country: Croatia
facility: Sisters of Mercy Clinical Hospital Centre
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, University of Amsterdam
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Paul-Peter Tak, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.