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Splenic Stimulation for RA

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ClinicalTrials.gov Identifier: NCT05003310
Recruitment Status : Recruiting
First Posted : August 12, 2021
Last Update Posted : October 26, 2021
Sponsor:
Collaborators:
NAMSA
Q2 Solutions
Information provided by (Responsible Party):
Galvani Bioelectronics

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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Device: Active Stimulation Device: Sham Stimulation Drug: Baricitinib Drug: Background Treatment Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
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
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Multipart Exploratory Study to Evaluate Splenic Nerve Stimulation in Patients With Rheumatoid Arthritis
Actual Study Start Date : October 19, 2021
Estimated Primary Completion Date : January 2029
Estimated Study Completion Date : January 2029

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active Stimulation; Period 1
Active stimulation for 12 weeks in addition to stable dose of csDMARD therapy.
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 in addition to stable dose of csDMARD therapy.
Device: Sham Stimulation
Sham stimulation will be provided during the period

Drug: Background Treatment
Stable dose of standard background treatment (e.g., csDMARD therapy)

Experimental: Open label active stimulation, Period 2
Open label active stimulation for 12 additional weeks in addition to stable dose of csDMARD therapy.
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)

Open label RA Drug, Period 2
Open label drug treatment with baricitinib for 12 weeks in addition to stable dose of csDMARD therapy.
Drug: Baricitinib
Baricitinib (2 mg) is administered daily during the period.

Drug: Background Treatment
Stable dose of standard background treatment (e.g., csDMARD therapy)

Experimental: RA drug combined with active stimulation, Period 3
Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.
Device: Active Stimulation
Stimulation will be turned ON and applied during each day of the period.

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

Drug: Background Treatment
Stable dose of standard background treatment (e.g., csDMARD therapy)

Experimental: Active stimulation combined with RA drug, Period 3
Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.
Device: Active Stimulation
Stimulation will be turned ON and applied during each day of the period.

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

Drug: Background Treatment
Stable dose of standard background treatment (e.g., csDMARD therapy)

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)




Primary Outcome Measures :
  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 Outcome Measures :
  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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   22 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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) including at least one TNF inhibitor.
  • Have an appropriate washout from previously used biological DMARDs or JAKi
  • Receiving treatment with standard dose(s) of conventional synthetic DMARD(s)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05003310


Contacts
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Contact: Operations Director +1 877 613 9001 clinical@galvani.bio

Locations
Layout table for location information
United States, Alabama
Pinnacle Research Group, LLC Recruiting
Anniston, Alabama, United States, 36207
Contact: Study Coordinator    256-236-0055 ext 116    rfields@pinnacletrials.com   
Principal Investigator: Vishala Chindalore, MD         
United States, New York
NYU Langone Recruiting
Brooklyn, New York, United States, 11201
Contact: Galvani Operations Director    877-613-9001    clinical@galvani.bio   
Principal Investigator: David Goddard, MD         
United States, Texas
St. David's Healthcare Recruiting
Austin, Texas, United States, 78705
Contact: SDH Office of Research; Research Dept    512-544-8070    Krishna.Saini@stdavids.com   
Principal Investigator: Robert J. Koval, MD         
Metroplex Clinical Research Center Recruiting
Dallas, Texas, United States, 75231
Contact: Recruitment Specialist    214-424-0405    info@mcrcdallas.com   
Principal Investigator: Roy Fleischmann, MD         
Sponsors and Collaborators
Galvani Bioelectronics
NAMSA
Q2 Solutions
Layout table for additonal information
Responsible Party: Galvani Bioelectronics
ClinicalTrials.gov Identifier: NCT05003310    
Other Study ID Numbers: GAL1040
First Posted: August 12, 2021    Key Record Dates
Last Update Posted: October 26, 2021
Last Verified: October 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Galvani Bioelectronics:
Electrical stimulation
random allocation
inflammation
active implantable medical device
Laparoscopy
antirheumatic agents
autonomic nervous system
feasibility studies
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases