ConsideRAte Study - Splenic Stimulation for RA

Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Device: Active Stimulation; Drug: Background Treatment; Device: Sham Stimulation; Drug: Baricitinib

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Operations Director; Phone Number: +1 877 613 9001; Email: clinical@galvani.bio

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Academic Medical Center (AMC) Dept of Rheumatology & Clinical Immunology
    • Contact: Study Coordinator
    • Principal Investigator: Sander Tas, MD
  • Eindhoven, Netherlands
    • Recruiting
    • Maxima Medical Center, MMC
    • Contact: Jasper Broen, MD
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Withdrawn
      • Pinnacle Research Group, LLC
  • California
    • Covina, California, United States, 91722
      • Recruiting
      • Medvin Research - Covina
      • Principal Investigator: Samy Metyas, MD
      • Contact: Study Coordinator; Phone Number: 626-869-5730; Email: Info@medvinresearch.com
    • Whittier, California, United States, 90602
      • Recruiting
      • Medvin Research - Whittier
      • Principal Investigator: Tien-I Karleen Su, MD
      • Contact: Study Coordinator; Phone Number: 562-758-6600; Email: Info@medvinresearch.com
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Recruiting
      • The Osteoporosis & Clinical Trials Center
      • Contact: Study Coordinator; Phone Number: 301-791-6680; Email: arthritis@rheumdocs.com
      • Principal Investigator: Mary Howell, MD
  • New York
    • Brooklyn, New York, United States, 11201
      • Recruiting
      • NYU Langone
      • Contact: Galvani Operations Director; Phone Number: 877-613-9001; Email: clinical@galvani.bio
      • Principal Investigator: David Goddard, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Cong-Qui Chu, MD; Phone Number: 503-494-8637
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16635
      • Recruiting
      • Altoona Center For Clinical Research
      • Principal Investigator: Alan Kivitz, MD
      • Contact: Study Coordinator; Phone Number: 800-924-7790
  • Texas
    • Allen, Texas, United States, 75013
      • Recruiting
      • Arthritis & Rheumatology Institute
      • Principal Investigator: Megha Patel-Banker, MD
      • Contact: Study Coordinator; Phone Number: 972-798-8553
    • Austin, Texas, United States, 78745
      • Recruiting
      • Tekton Research
      • Principal Investigator: Paul Pickrell, MD
      • Contact: Study Coordinator; Phone Number: 512-388-5717; Email: trials@tektonresearch.com
    • Austin, Texas, United States, 78705
      • Recruiting
      • St. David's Healthcare
      • Contact: SDH Office of Research; Research Dept; Phone Number: 512-544-8070; Email: Krishna.Saini@stdavids.com
      • Principal Investigator: Robert J. Koval, MD
    • Dallas, Texas, United States, 75231
      • Withdrawn
      • Metroplex Clinical Research Center
    • Mesquite, Texas, United States, 75150
      • Recruiting
      • SouthWest Rheumatology Research
      • Principal Investigator: Atul Singhal, MD
      • Contact: Study Coordiinator; Phone Number: 972-288-2600; Email: jointpain@swrr.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Long-term Follow-up, Period 4; Standard of care treatments with or without stimulation	Device: Active Stimulation; Stimulation will be turned ON and applied during each day of the period.; Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy)
Experimental: Active Stimulation; Period 1; Active stimulation for 12 weeks	Device: Active Stimulation; Stimulation will be turned ON and applied during each day of the period.; Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy)
Sham Comparator: Sham Stimulation; Period 1; Sham stimulation for 12 weeks	Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy); Device: Sham Stimulation; Sham stimulation will be provided during the period
Experimental: Open label active stimulation, Period 2; Open label active stimulation for 12 additional weeks	Device: Active Stimulation; Stimulation will be turned ON and applied during each day of the period.; Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy)
Other: Open label RA Drug, Period 2; Open label drug treatment with baricitinib for 12 weeks	Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy); Drug: Baricitinib; Baricitinib (2 mg) is administered daily during the period.
Experimental: RA drug combined with active stimulation, Period 3; Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks	Device: Active Stimulation; Stimulation will be turned ON and applied during each day of the period.; Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy); Drug: Baricitinib; Baricitinib (2 mg) is administered daily during the period.
Experimental: Active stimulation combined with RA drug, Period 3; Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks	Device: Active Stimulation; Stimulation will be turned ON and applied during each day of the period.; Drug: Background Treatment; Stable dose of standard background treatment (e.g., csDMARD therapy); Drug: Baricitinib; Baricitinib (2 mg) is administered daily during the period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events [Safety and Tolerability]	Adverse Events (AEs) may include clinically significant findings from Laboratory Safety Assessments (clinical chemistry and hematology), vital signs (blood pressure, heart rate, respiratory rate, and body temperature), and 12-Lead EKG	Up through the end of Period 1 (Period 1 is up to 12 weeks duration)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]		During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP)		Baseline to 12 weeks (Period 1)
Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay		Baseline to 12 weeks (Period 1)
Change in the level of LPS-inducible release of TNFα in whole blood assay		Baseline to 24 weeks (Period 2)
Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay		Baseline to 12 weeks (Period 1)
Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay		Baseline to 24 weeks (Period 2)
Change in the level of LPS-inducible release of IL-8 in whole blood assay		Baseline to 12 weeks (Period 1)
Change in the level of LPS-inducible release of IL-8 in whole blood assay		Baseline to 24 weeks (Period 2)
Change in the level of LPS-inducible release of IL-17 in whole blood assay		Baseline to 12 weeks (Period 1)
Change in the level of LPS-inducible release of IL-17 in whole blood assay		Baseline to 24 weeks (Period 2)
Change in DAS28-CRP		Baseline to 24 weeks (Period 2)
Change in DAS28-CRP		Baseline to 36 weeks (Period 3)
Change in DAS28-CRP		Baseline to 48 weeks (Period 3)
Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score		Baseline to 12 weeks (Period 1)
Change in HAQ-DI score		Baseline to 24 weeks (Period 2)
Change in HAQ-DI score		Baseline to 36 weeks (Period 3)
Change in HAQ-DI score		Baseline to 48 weeks (Period 3)
Change in Short Form 36 (SF-36) physical component score		Baseline to 12 weeks (Period 1)
Change in SF-36 physical component score		Baseline to 24 weeks (Period 2)
Change in SF-36 physical component score		Baseline to 36 weeks (Period 3)
Change in SF-36 physical component score		Baseline to 48 weeks (Period 3)
Change in SF-36 mental component score		Baseline to 12 weeks (Period 1)
Change in SF-36 mental component score		Baseline to 24 weeks (Period 2)
Change in SF-36 mental component score		Baseline to 36 weeks (Period 3)
Change in SF-36 mental component score		Baseline to 48 weeks (Period 3)
Change in SF-36 domain score		Baseline to 12 weeks (Period 1)
Change in SF-36 domain score		Baseline to 24 weeks (Period 2)
Change in SF-36 domain score		Baseline to 36 weeks (Period 3)
Change in SF-36 domain score		Baseline to 48 weeks (Period 3)
To evaluate the usability of the external Galvani System devices and accessories	Summarize feedback collected on a questionnaire pertaining to the use of the external Galvani System devices	Through 48 weeks
To evaluate the participants' perception of therapy and sensation	A form is provided to participants at each visit after randomization to describe any sensations that may be associated with the Galvani System	Through 48 weeks
Evaluate device performance as assessed by tabulation of device deficiencies		Through 48 weeks
Change in DAS28-CRP in participants who remain on active stimulation during Period 2		week 12 to week 24
Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2		Time Frame: Week 24
Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2		week 12 to week 24
Incidence of a change in DAS28-CRP greater than 1.2 units in participants who are given Drug treatment with baricitinib during Period 2		week 12 to week 24
Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2		Week 24

Collaborators and Investigators

• Sponsor: Galvani Bioelectronics
• Collaborators: NAMSA; Q2 Solutions

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2021
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: autonomic nervous system; inflammation; Electrical stimulation; Laparoscopy; feasibility studies; antirheumatic agents; random allocation; active 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: GAL1040

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes