Rheumatoid ArthritisNCT03437473
Safety and Efficacy of Vagus Nerve Stimulator in Patients With Rheumatoid Arthritis (RA)
A study testing SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System in people with Rheumatoid Arthritis, run by SetPoint Medical Corporation at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 75 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 4 sitesUnited States
- Study dates
- 6 Mar 2018to 10 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female and 22-75 years of age, inclusive
- Have provided informed consent
- Have a diagnosis of adult-onset rheumatoid arthritis as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010)
- Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints and CDAI score >10
- 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:
- experienced insufficient efficacy or loss of efficacy
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- experienced intolerance of such treatment
- 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
- 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
Who cannot join
- Have taken the following within the defined time period prior to screening visit:
- 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
- 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
- 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
- Documented significant psychiatric illness or substance abuse
- Active infection requiring treatment with antibiotics
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- Uncontrolled hypertension
- Uncontrolled diabetes
- History of stroke
- 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
- Known neurological syndromes
- Known atherosclerotic disease including contralateral carotid artery
- BMI <18.5 or >35
- Any condition per the investigator's clinical judgment that precludes participation in the study
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Arthritis & Rheumatic Disease Specialties
Aventura, Florida, 33180
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Northwell Health Division of Rheumatology
Great Neck, New York, 11021
Florida Medical Clinic, P.A.
Zephyrhills, Florida, 33542
About this study
Official title: A Randomized Controlled Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway SystemDevice
Also called SetPoint System
Active Implantable Vagus Nerve Stimulation device.
| Study group | Role | What they receive |
|---|---|---|
| Active stimulation QD | Active comparator | Not described Receives: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
| Active stimulation QID | Active comparator | Not described Receives: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
| No stimulation | Sham comparator | Not described Receives: Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of Adverse Events
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
Measured: Enrollment to Week 12
Secondary outcomes (4)
change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP)
comparison between the active device group and the inactive device group of the change in DAS28-CRP
Measured: change from baseline at Day 0 and Week 12
change in American College of Rheumatology (ACR) 20, 50 and 70 response rates
comparison between the active device group and the inactive device group of the change in ACR 20/50/70
Measured: change from baseline at Day 0 and Week 12
change in European League Against Rheumatism (EULAR) response and remission rate
comparison between the active device group and the inactive device group of the change in EULAR
Measured: change from baseline at Day 0 and Week 12
change in hand MRI
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
Measured: change from baseline at Day 0 and Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start6 Mar 2018
- Primary completion10 Dec 2018
- Study completion10 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- SetPoint Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark Genovese, MD, Study director, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437473
- Sponsor's protocol ID
- SPM-008
- Status last verified
- Dec 2018
- First submitted
- 6 Feb 2018
- Last updated
- 27 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Genovese MC, Gaylis NB, Sikes D, Kivitz A, Lewis Horowitz D, Peterfy C, Glass EV, Levine YA, Chernoff D. Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study. Lancet Rheumatol. 2020 Sep;2(9):e527-e538. doi: 10.1016/S2665-9913(20)30172-7. Epub 2020 Jul 28.
PubMed 38273617
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study of the Safety and Efficacy of Neurostimulation Using a Vagus Nerve Stimulation Device in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03437473
- Acronym / sponsor ID
- SPM-008
- Conditions
- Rheumatoid Arthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- SetPoint Medical CorporationIndustry (pharma, biotech, devices)
- Study start
- 6 Mar 2018 (actual)
- Primary completion
- 10 Dec 2018 (actual)
- Study completion
- 10 Dec 2018 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active stimulation QD | Active comparator | Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
| Active stimulation QID | Active comparator | Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
| No stimulation | Sham comparator | Device: SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System |
Who may qualify
- Ages
- 22 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female and 22-75 years of age, inclusive
- Have provided informed consent
- Have a diagnosis of adult-onset rheumatoid arthritis as defined by the 2010 ACR/EULAR classification criteria (Aletaha, 2010)
- Have moderately to severely active RA defined by at least 4/28 tender and 4/28 swollen joints and CDAI score >10
- 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:
Key exclusion criteria (14 listed)
- Have taken the following within the defined time period prior to screening visit:
- 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
- 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
- Documented significant psychiatric illness or substance abuse
- Active infection requiring treatment with antibiotics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway SystemAlso: SetPoint SystemActive Implantable Vagus Nerve Stimulation device. | Device | Active stimulation QD, Active stimulation QID, No stimulation |
Primary outcome
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
4 secondary outcomes
change in Disease Activity Score (DAS) 28 - C-reactive protein (CRP)
Time frame: change from baseline at Day 0 and Week 12
change in American College of Rheumatology (ACR) 20, 50 and 70 response rates
Time frame: change from baseline at Day 0 and Week 12
change in European League Against Rheumatism (EULAR) response and remission rate
Time frame: change from baseline at Day 0 and Week 12
change in hand MRI
Time frame: change from baseline at Day 0 and Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2018.
- Derived from this study: PubMed 38273617Genovese MC, Gaylis NB, Sikes D, Kivitz A, Lewis Horowitz D, Peterfy C, Glass EV, Levine YA, Chernoff D. Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study. Lancet Rheumatol. 2020 Sep;2(9):e527-e538. doi: 10.1016/S2665-9913(20)30172-7. Epub 2020 Jul 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Genovese, MD study director
Stanford University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SetPoint Medical Neurostimulation of the Cholinergic Anti-inflammatory Pathway System in people with Rheumatoid Arthritis, run by SetPoint Medical Corporation at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of Adverse Events (time frame: Enrollment to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03437473, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.