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Safety and Efficacy of Vagus Nerve Stimulator in Patients With Rheumatoid Arthritis (RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03437473
Recruitment Status : Completed
First Posted : February 19, 2018
Last Update Posted : December 27, 2018
Sponsor:
Information provided by (Responsible Party):
SetPoint Medical Corporation

Tracking Information
First Submitted Date  ICMJE February 6, 2018
First Posted Date  ICMJE February 19, 2018
Last Update Posted Date December 27, 2018
Actual Study Start Date  ICMJE March 6, 2018
Actual Primary Completion Date December 10, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
incidence of Adverse Events [ Time Frame: Enrollment to Week 12 ]
treatment-emergent incidence rates of Adverse Events, Adverse Device Effects, Serious Adverse Events, Serious Adverse Device Effects, Unanticipated Adverse Device Effects, and Unanticipated Serious Adverse Device Effects
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2018)
  • change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP) [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in DAS28-CRP
  • change in American College of Rheumatology (ACR) 20, 50 and 70 response rates [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in ACR 20/50/70
  • change in European League Against Rheumatism (EULAR) response and remission rate [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in EULAR
  • change in hand MRI [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in Outcomes Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS) hand MRI index of synovitis
Original Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2018)
  • change in Disease Activity Score (DAS) 28 - C-reactove protein (CRP) [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in DAS28-CRP
  • change in American College of Rheumatology (ACR) 20, 50 and 70 response rates [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in ACR 20/50/70
  • change in European League Against Rheumatism (EULAR) response and remission rate [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in EULAR
  • change in hand MRI [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in Outcomes Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS) hand MRI index of synovitis
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: February 12, 2018)
  • change in Clinical Disease Activity Index [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in Clinical Disease Activity Index (CDAI)
  • change in Beck Depression Inventory II [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in Beck Depression Inventory II
  • change in Vectra DA score [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in Vectra DA score
  • change in heart rate variability [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in heart rate variability as assessed by standard deviation of R-R intervals (SDNN) and root mean square of differences between successive R-R intervals [RMSSD])
  • change in heart rate variability [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in heart rate variability as assessed by frequency domain parameters (absolute and normalized high frequency (HF) and low frequency (LF) power
  • change in Bacterial lipopolysaccharide (LPS)-induced Tumor Necrosis Factor (TNF) production [ Time Frame: change from baseline at Day 0 and Week 12 ]
    comparison between the active device group and the inactive device group of the change in in vitro LPS-induced TNF production in whole blood
  • pre-implant to end of study changes in DAS 28-CRP [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in DAS 28-CRP
  • pre-implant to end of study changes in ACR 20, 50, 70 [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in ACR 20, 50, 70
  • pre-implant to end of study changes in EULAR [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in EULAR
  • pre-implant to end of study changes in CDAI (Clinical Disease Activity Index) [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in CDAI
  • pre-implant to end of study changes in OMERACT RAMRIS hand MRI index of osteitis and erosions [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in OMERACT RAMRIS
  • pre-implant to end of study changes in CARLOS MRI cartilage loss [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in CARLOS MRI cartilage loss
  • pre-implant to end of study changes in Beck Depression Inventory II (BDI-II) [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in BDI-II
  • pre-implant to end of study changes in Vectra DA score [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in Vectra DA score
  • pre-implant to end of study changes in heart rate variability [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in heart rate variability as assessed by standard deviation of R-R intervals (SDNN) and root mean square of differences between successive R-R intervals [RMSSD])
  • pre-implant to end of study changes in heart rate variability [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in heart rate variability as assessed by frequency domain parameters (absolute and normalized high frequency (HF) and low frequency (LF) power
  • pre-implant to end of study changes in TNF production [ Time Frame: change from pre-implant, Week -6, to Week 12 ]
    comparison between the active device group and the inactive device group of the change in in vitro LPS-induced TNF production in whole blood
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Vagus Nerve Stimulator in Patients With Rheumatoid Arthritis (RA)
Official Title  ICMJE A Randomized Controlled Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis
Brief Summary Multi-site, first-in-human study to assess safety and efficacy of an active implantable Vagus Nerve Stimulation (VNS) device in 15 adult patients with active moderate-to-severe rheumatoid arthritis who have had an incomplete response or intolerability to at least two different mechanisms of action.
Detailed Description

This is a two-stage study where Stage 1 is open label, and Stage 2 is randomized and sham controlled where the sites and subjects are blinded to treatment. Three subjects will be enrolled in Stage 1 of the study. And 12 subjects will be enrolled in Stage 2. Subjects will be treated for a total of 12 weeks.

Subjects will be asked to visit the clinic at day 0, week 1-6, week 8 and week 12. During these visits, the following activities will be conducted: standard patient and physician assessments of RA activity, blood sample collection for RA biomarkers, and a hand MRI.

Subjects who complete the study will have the option to enroll in a long-term extension study. Subjects that do not participate in the extension study can opt to either have their device permanently inactivated and left in place or have the device surgically explanted.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Device Feasibility
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
Active Implantable Vagus Nerve Stimulation device.
Other Name: SetPoint System
Study Arms  ICMJE
  • Active Comparator: Active stimulation QD
    Intervention: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
  • Active Comparator: Active stimulation QID
    Intervention: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
  • Sham Comparator: No stimulation
    Intervention: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 26, 2018)
14
Original Estimated Enrollment  ICMJE
 (submitted: February 12, 2018)
15
Actual Study Completion Date  ICMJE December 10, 2018
Actual Primary Completion Date December 10, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female and 22-75 years of age, inclusive
  2. Have provided informed consent
  3. Have a diagnosis of adult-onset rheumatoid arthritis as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010)
  4. Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints and CDAI score >10
  5. Have been treated at approved doses with at least 2 biologic DMARDs and/or new targeted synthetic DMARDs (e.g. JAK inhibition) for at least 3 months and either:

    1. experienced insufficient efficacy or loss of efficacy
    2. experienced intolerance of such treatment
  6. Have had regular use of at least 1 conventional DMARDs for at least the 12 weeks prior to study entry with a continuous, non-changing dose for at least 8 weeks prior to screening visit
  7. Women of childbearing potential must not be pregnant at the time of screening and must agree to use a double barrier method of contraception throughout the study

Exclusion Criteria:

  1. Have taken the following within the defined time period prior to screening visit:

    i. Rituximab: 6 months ii. Infliximab, golimumab, adalimumab, certolizumab pegol, tocilizumab: 60 days iii. Abatacept, etanercept, anakinra: 30 days iv. Tofacitinib: 30 days v. Investigational biologic agents: 6 months for depleting agents, 60 days for others vi. Investigational small molecules: 5 times the pharmacokinetic half-life or 30 days, whichever is longer vii. Intra-articular corticosteroid injection: 30 days

  2. Are currently receiving corticosteroids at doses greater than 10 mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening visit
  3. Have started treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of screening visit
  4. Documented significant psychiatric illness or substance abuse
  5. Active infection requiring treatment with antibiotics
  6. Uncontrolled hypertension
  7. Uncontrolled diabetes
  8. History of stroke
  9. Known cardiac disease, including cardiomyopathy with ejection fraction <40%, recent myocardial infarction or unstable angina, or heart failure with New York Heart Association class III or IV symptoms
  10. Known neurological syndromes
  11. Known atherosclerotic disease including contralateral carotid artery
  12. BMI <18.5 or >35
  13. Any condition per the investigator's clinical judgment that precludes participation in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 22 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03437473
Other Study ID Numbers  ICMJE SPM-008
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party SetPoint Medical Corporation
Study Sponsor  ICMJE SetPoint Medical Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mark Genovese, MD Stanford University
PRS Account SetPoint Medical Corporation
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP