Clinical trial NCT05003310: ConsideRAte Study - Splenic Stimulation for RA
Official title: Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rheumatoid Arthritis
Keywords: Electrical stimulation
random allocation
inflammation
active implantable medical device
Laparoscopy
antirheumatic agents
autonomic nervous system
feasibility studies
Lead sponsor: Galvani Bioelectronics
Sponsor class: INDUSTRY
Collaborators: name: NAMSA
name: Q2 Solutions
First posted: 2021-08-12
Enrollment: 28
Sex: ALL
Minimum age (years): 22
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multicenter study with 4 periods. Period 1 is a randomized, controlled double-blind period where participants are assigned randomly to either active or sham stimulation. During the open-label Periods 2 through 4, participants are assigned treatment based on responses to treatments in the prior period
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and effects of stimulating the splenic neurovascular bundle (NVB) with the Galvani System, which consists of a lead, implantable pulse generator, external components and accessories. The study will consist of 4 study periods, including a Randomized Control Trial period (Period 1), an Open Label period (Period 2), a Treat-to-target period (Period 3), and a Long-term Follow-up period (Period 4). Participants eligible for implant will have active rheumatoid arthritis (RA) and have an inadequate response or intolerance to at least two biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) or JAK inhibitors (JAKis). A sufficient number of participants will be enrolled so that approximately 28 participants will undergo device implantation.

Detailed description: Participants with active rheumatoid arthritis (RA) who receive the implantable system will be randomly assigned to receive either active stimulation or sham-stimulation for 12 weeks (Period 1).

Following Period 1, all participants will enter an open label phase (Period 2) during which participants who responded to stimulation will continue on stimulation; whereas participants who received sham stimulation, or were stimulation non-responders, will receive a market-approved RA drug for 12 weeks.

At the end of Period 2, participants who respond to their Period 2 therapy but still exhibit signs and symptoms of RA will enter the Treat-to-target period (Period 3); others will proceed to Period 4 (Long-term Follow-up). During the Treat-to-Target period, participants will be treated with dual therapy (stimulation in combination with the market-approved RA drug) for up to 24 weeks.

Period 4 provides long term safety follow up for all study participants for a period of 5 years. Participants may receive stimulation in combination with other approved and standard of care therapies, subject to a favorable benefit-risk assessment in the judgement of the treating rheumatologist.

Eligibility criteria: Inclusion Criteria:

* RA of at least six months duration, per 2010 ACR/EULAR criteria
* Male or female participants, 22-75 years of age
* Active RA
* Inadequate Response to at least 2 biologic DMARDs and/or JAK-inhibitors (JAKis) including at least one TNF inhibitor
* Have an appropriate washout from previously used biological DMARDs or JAKi
* Receiving current treatment with standard dose(s) of conventional synthetic DMARD(s) or have documented history of failure due to ineffectiveness or intolerance

Exclusion Criteria:

* Inability to provide informed consent
* Significant psychiatric disease or substance abuse
* History of unilateral or bilateral vagotomy
* Active or latent tuberculosis
* Known infection with human immunodeficiency virus (HIV); current acute or chronic hepatitis B or hepatitis C; previous hepatitis B
* Positive SARS COV 2 PCR screening test for COVID-19 infection (at the point of screening for this study)
* Currently implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators)
* Previous splenectomy

Primary outcomes:
measure: Incidence of Adverse Events [Safety and Tolerability]
timeFrame: Up through the end of Period 1 (Period 1 is up to 12 weeks duration)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)
Secondary outcomes:
measure: Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP)
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in the level of LPS-inducible release of TNFα in whole blood assay
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in the level of LPS-inducible release of IL-8 in whole blood assay
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in the level of LPS-inducible release of IL-8 in whole blood assay
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in the level of LPS-inducible release of IL-17 in whole blood assay
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in the level of LPS-inducible release of IL-17 in whole blood assay
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in DAS28-CRP
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in DAS28-CRP
timeFrame: Baseline to 36 weeks (Period 3)
measure: Change in DAS28-CRP
timeFrame: Baseline to 48 weeks (Period 3)
measure: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in HAQ-DI score
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in HAQ-DI score
timeFrame: Baseline to 36 weeks (Period 3)
measure: Change in HAQ-DI score
timeFrame: Baseline to 48 weeks (Period 3)
measure: Change in Short Form 36 (SF-36) physical component score
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in SF-36 physical component score
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in SF-36 physical component score
timeFrame: Baseline to 36 weeks (Period 3)
measure: Change in SF-36 physical component score
timeFrame: Baseline to 48 weeks (Period 3)
measure: Change in SF-36 mental component score
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in SF-36 mental component score
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in SF-36 mental component score
timeFrame: Baseline to 36 weeks (Period 3)
measure: Change in SF-36 mental component score
timeFrame: Baseline to 48 weeks (Period 3)
measure: Change in SF-36 domain score
timeFrame: Baseline to 12 weeks (Period 1)
measure: Change in SF-36 domain score
timeFrame: Baseline to 24 weeks (Period 2)
measure: Change in SF-36 domain score
timeFrame: Baseline to 36 weeks (Period 3)
measure: Change in SF-36 domain score
timeFrame: Baseline to 48 weeks (Period 3)
measure: To evaluate the usability of the external Galvani System devices and accessories
timeFrame: Through 48 weeks
measure: To evaluate the participants' perception of therapy and sensation
timeFrame: Through 48 weeks
measure: Evaluate device performance as assessed by tabulation of device deficiencies
timeFrame: Through 48 weeks
measure: Change in DAS28-CRP in participants who remain on active stimulation during Period 2
timeFrame: week 12 to week 24
measure: Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2
timeFrame: Time Frame: Week 24
measure: Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2
timeFrame: week 12 to week 24
measure: Incidence of a change in DAS28-CRP greater than 1.2 units in participants who are given Drug treatment with baricitinib during Period 2
timeFrame: week 12 to week 24
measure: Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2
timeFrame: Week 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Covina
country: United States
facility: Medvin Research - Covina
state: California
city: Whittier
country: United States
facility: Medvin Research - Whittier
state: California
city: Hagerstown
country: United States
facility: The Osteoporosis & Clinical Trials Center
state: Maryland
city: Brooklyn
country: United States
facility: NYU Langone
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Altoona
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Allen
country: United States
facility: Arthritis & Rheumatology Institute
state: Texas
city: Austin
country: United States
facility: St. David's Healthcare
state: Texas
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research
state: Texas
city: Amsterdam
country: Netherlands
facility: Academic Medical Center (AMC) Dept of Rheumatology & Clinical Immunology
city: Eindhoven
country: Netherlands
facility: Maxima Medical Center, MMC
Study officials:
References: