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NCT Number: NCT05003310

ConsideRAte Study - Splenic Stimulation for RA

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Inflammation Joint Diseases Musculoskeletal Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

22 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Academic Medical Center (AMC) Dept of Rheumatology & Clinical Immunology, Amsterdam, Netherlands

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Active stimulation

Device

Stimulation will be turned ON and applied during each day of the period.

Sham stimulation

Device

Sham stimulation will be provided during the period

Baricitinib

Drug

Baricitinib (2 mg) is administered daily during the period.

background treatment

Drug

Stable dose of standard background treatment (e.g., csDMARD therapy)

Primary outcomes

  1. Incidence of Adverse Events [Safety and Tolerability]

    Time frame: Up through the end of Period 1 (Period 1 is up to 12 weeks duration)

    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

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time frame: During Period 2 (Period 2 is up to 12 weeks in duration beyond Period 1)

  3. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time frame: During Period 3 (Period 3 is up to 24 weeks in duration beyond Period 2)

  4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time frame: During Period 4 (Period 4 is up to 5 years in duration beyond Period 3)

Secondary outcomes

  1. Change in the 28 Joint Disease Activity Score 28 - C reactive protein (DAS28-CRP)

    Time frame: Baseline to 12 weeks (Period 1)

  2. Change in the level of Lipopolysaccharide (LPS)-inducible release of Tumor Necrosis Factor (TNFα) in whole blood assay

    Time frame: Baseline to 12 weeks (Period 1)

  3. Change in the level of LPS-inducible release of TNFα in whole blood assay

    Time frame: Baseline to 24 weeks (Period 2)

  4. Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay

    Time frame: Baseline to 12 weeks (Period 1)

  5. Change in the level of LPS-inducible release of Interleukin 6 (IL-6) in whole blood assay

    Time frame: Baseline to 24 weeks (Period 2)

  6. Change in the level of LPS-inducible release of IL-8 in whole blood assay

    Time frame: Baseline to 12 weeks (Period 1)

  7. Change in the level of LPS-inducible release of IL-8 in whole blood assay

    Time frame: Baseline to 24 weeks (Period 2)

  8. Change in the level of LPS-inducible release of IL-17 in whole blood assay

    Time frame: Baseline to 12 weeks (Period 1)

  9. Change in the level of LPS-inducible release of IL-17 in whole blood assay

    Time frame: Baseline to 24 weeks (Period 2)

  10. Change in DAS28-CRP

    Time frame: Baseline to 24 weeks (Period 2)

  11. Change in DAS28-CRP

    Time frame: Baseline to 36 weeks (Period 3)

  12. Change in DAS28-CRP

    Time frame: Baseline to 48 weeks (Period 3)

  13. Change in Health Assessment Questionnaire Disability Index (HAQ-DI) score

    Time frame: Baseline to 12 weeks (Period 1)

  14. Change in HAQ-DI score

    Time frame: Baseline to 24 weeks (Period 2)

  15. Change in HAQ-DI score

    Time frame: Baseline to 36 weeks (Period 3)

  16. Change in HAQ-DI score

    Time frame: Baseline to 48 weeks (Period 3)

  17. Change in Short Form 36 (SF-36) physical component score

    Time frame: Baseline to 12 weeks (Period 1)

  18. Change in SF-36 physical component score

    Time frame: Baseline to 24 weeks (Period 2)

  19. Change in SF-36 physical component score

    Time frame: Baseline to 36 weeks (Period 3)

  20. Change in SF-36 physical component score

    Time frame: Baseline to 48 weeks (Period 3)

  21. Change in SF-36 mental component score

    Time frame: Baseline to 12 weeks (Period 1)

  22. Change in SF-36 mental component score

    Time frame: Baseline to 24 weeks (Period 2)

  23. Change in SF-36 mental component score

    Time frame: Baseline to 36 weeks (Period 3)

  24. Change in SF-36 mental component score

    Time frame: Baseline to 48 weeks (Period 3)

  25. Change in SF-36 domain score

    Time frame: Baseline to 12 weeks (Period 1)

  26. Change in SF-36 domain score

    Time frame: Baseline to 24 weeks (Period 2)

  27. Change in SF-36 domain score

    Time frame: Baseline to 36 weeks (Period 3)

  28. Change in SF-36 domain score

    Time frame: Baseline to 48 weeks (Period 3)

  29. To evaluate the usability of the external Galvani System devices and accessories

    Time frame: Through 48 weeks

    Summarize feedback collected on a questionnaire pertaining to the use of the external Galvani System devices

  30. To evaluate the participants' perception of therapy and sensation

    Time frame: Through 48 weeks

    A form is provided to participants at each visit after randomization to describe any sensations that may be associated with the Galvani System

  31. Evaluate device performance as assessed by tabulation of device deficiencies

    Time frame: Through 48 weeks

  32. Change in DAS28-CRP in participants who remain on active stimulation during Period 2

    Time frame: week 12 to week 24

  33. Incidence of participants who remain on active stimulation achieving DAS28-CRP score <2.6 at the end of Period 2

    Time frame: Time Frame: Week 24

  34. Change in DAS28-CRP in participants who are given Drug treatment with baricitinib during Period 2

    Time frame: week 12 to week 24

  35. Incidence of a change in DAS28-CRP greater than 1.2 units in participants who are given Drug treatment with baricitinib during Period 2

    Time frame: week 12 to week 24

  36. Incidence of participants who are given drug treatment with baricitinib achieving DAS28-CRP score <2.6 at the end of Period 2

    Time frame: Week 24

Study contacts

Contact information is provided by the study sponsor or research team.

Operations Director

CONTACT

[email protected]

+1 877 613 9001

Sponsors and collaborators

Lead sponsor

Galvani Bioelectronics

Industry

Collaborators

  • NAMSA
  • Q2 Solutions

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2027
Study completion
2032
First posted
Aug 12, 2021
Registry last updated
May 22, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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