Safety of Splenic Stimulation for RA

A Single Arm Pilot Study to Evaluate the Safety and Feasibility of Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis Using an Active Implantable Device

This study will evaluate the safety and tolerability of stimulating the splenic neurovascular bundle (NVB) with the Galvani System, which consists of a lead, implantable pulse generator, external components and accessories. 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). Five participants will be implanted with the device and receive neurostimulation for 12 weeks.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Device: Active Stimulation

Detailed Description

The study will be an open-label single-arm study to evaluate the safety and tolerability of Galvani's neuromodulation system. Participants with active rheumatoid arthritis (RA) will be implanted with the Galvani system and receive active stimulation for 12 weeks. The total study duration in the study for each participant is approximately 5 months, with a 4-week screening period, 4 weeks recovery from surgery and a 12-week 'treatment' period. The participants will return to the clinic on pre-defined days for follow-up visits during the trial period. At Days 42 and/or Day 56, if study participants are not responding to stimulation, stimulation parameters might be adapted. At the end of the study (Day-84), participants will enroll in a long-term follow-up study up to 5-years after enrollment in this study.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Operations Director; Phone Number: +44 (0)800 3688514; 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
• United Kingdom
  • Glasgow, United Kingdom, G12 OXH
    • Recruiting
    • Greater Glasgow Health Board
    • Contact: Operations Director; Phone Number: +44 (0)800 3688514; Email: clinical@galvani.bio

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult-onset RA of at least six months duration
• Male or female participants, 22-75 years of age
• Active RA
• Inadequate Response to at least 2 biologic DMARDs and/or JAK- inhibitors (JAKis)
• Have an appropriate washout from previously used biological DMARDs or JAKi
• A female participant should have no child-bearing potential

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.
• Currently implanted electrically active medical devices (e.g., cardiac pacemakers, automatic implantable cardioverter-defibrillators).
• Previous splenectomy
• Any investigational small molecule drug or biological within 2 weeks or 2 half-lives whichever is longer, before surgery.
• Uncontrolled other inflammatory diseases
• Current/recurrent infections that in the opinion of the PI risk>benefit.
• History of cancer within the past 5 years, except non-malignant skin cancer.
• Chronic use of morphine or oxicodone

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Stimulation; Active stimulation for 12 weeks	Device: Active Stimulation; The Galvani System will be implanted in eligible participants, and stimulation will be turned ON

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of the Galvani system	Incidence and relatedness of Adverse Events (AEs), which 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 ECG	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of stimulation on the change in pharmacodynamic and response biomarkers	Changes from baseline (Day 1) in the levels of LPS-inducible cytokine/ chemokine release, in whole blood assay at different timepoints after start of stimulation	Day 1 to week 12
To evaluate the usability of the external Galvani System devices and accessories	Summarize feedback collected on questionnaires pertaining to the use of the external Galvani System devices	12 weeks
To evaluate the participants' perception of therapy and sensation	Summarize feedback collected on questionnaires	12 weeks
Evaluate device performance	Tabulation of device deficiencies	12 weeks

Collaborators and Investigators

• Sponsor: Galvani Bioelectronics
• Collaborators: NAMSA

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: July 5, 2021
• First Posted (Actual): July 9, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: autonomic nervous system; inflammation; Electrical stimulation; Laparoscopy; feasibility studies; antirheumatic agents; 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: GAL1039

Drug and device information, study documents

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