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Splenic Stimulation for RA

Primary Purpose

Rheumatoid Arthritis

Status

Recruiting

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

Active Stimulation

Sham Stimulation

Baricitinib

Background Treatment

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Electrical stimulation, random allocation, inflammation, active implantable medical device, Laparoscopy, antirheumatic agents, autonomic nervous system, feasibility studies

Eligibility Criteria

22 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Pinnacle Research Group, LLC
Medvin Research - CovinaRecruiting
Medvin Research - WhittierRecruiting
The Osteoporosis & Clinical Trials CenterRecruiting
NYU LangoneRecruiting
Altoona Center for Clinical ResearchRecruiting
Arthritis & Rheumatology InstituteRecruiting
St. David's HealthcareRecruiting
Tekton ResearchRecruiting
Metroplex Clinical Research CenterRecruiting
Southwest Rheumatology ResearchRecruiting
Academic Medical Center (AMC) Dept of Rheumatology & Clinical ImmunologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Sham Comparator

Experimental

Other

Experimental

Other

Arm Label

Active Stimulation; Period 1

Sham Stimulation; Period 1

Open label active stimulation, Period 2

Open label RA Drug, Period 2

RA drug combined with active stimulation, Period 3

Active stimulation combined with RA drug, Period 3

Long-term Follow-up, Period 4

Arm Description

Active stimulation for 12 weeks in addition to stable dose of csDMARD therapy.

Sham stimulation for 12 weeks in addition to stable dose of csDMARD therapy.

Open label active stimulation for 12 additional weeks in addition to stable dose of csDMARD therapy.

Open label drug treatment with baricitinib for 12 weeks in addition to stable dose of csDMARD therapy.

Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.

Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.

Standard of care treatments with or without stimulation

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

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

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

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

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

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

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

Change in DAS28-CRP

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

Change in HAQ-DI score

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

Change in SF-36 physical component score

Change in SF-36 mental component score

Change in SF-36 domain score

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

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

Evaluate device performance as assessed by tabulation of device deficiencies

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

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

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

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

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

Full Information

NCT ID

NCT05003310

First Posted

July 5, 2021

Last Updated

July 27, 2023

Sponsor

Galvani Bioelectronics

Collaborators

NAMSA, Q2 Solutions

1. Study Identification

Unique Protocol Identification Number

NCT05003310

Brief Title

Splenic Stimulation for RA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 19, 2021 (Actual)

Primary Completion Date

January 2029 (Anticipated)

Study Completion Date

January 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Galvani Bioelectronics

Collaborators

NAMSA, Q2 Solutions

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Electrical stimulation, random allocation, inflammation, active implantable medical device, Laparoscopy, antirheumatic agents, autonomic nervous system, feasibility studies

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Sequential Assignment

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

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active Stimulation; Period 1

Arm Type

Experimental

Arm Description

Active stimulation for 12 weeks in addition to stable dose of csDMARD therapy.

Arm Title

Sham Stimulation; Period 1

Arm Type

Sham Comparator

Arm Description

Sham stimulation for 12 weeks in addition to stable dose of csDMARD therapy.

Arm Title

Open label active stimulation, Period 2

Arm Type

Experimental

Arm Description

Open label active stimulation for 12 additional weeks in addition to stable dose of csDMARD therapy.

Arm Title

Open label RA Drug, Period 2

Arm Type

Other

Arm Description

Open label drug treatment with baricitinib for 12 weeks in addition to stable dose of csDMARD therapy.

Arm Title

RA drug combined with active stimulation, Period 3

Arm Type

Experimental

Arm Description

Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.

Arm Title

Active stimulation combined with RA drug, Period 3

Arm Type

Experimental

Arm Description

Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks. Participants will also receive a stable dose of csDMARD therapy.

Arm Title

Long-term Follow-up, Period 4

Arm Type

Other

Arm Description

Standard of care treatments with or without stimulation

Intervention Type

Device

Intervention Name(s)

Active Stimulation

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

Sham Stimulation

Intervention Description

Sham stimulation will be provided during the period

Intervention Type

Drug

Intervention Name(s)

Baricitinib

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Background Treatment

Intervention Description

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

Primary Outcome Measure Information:

Title

Incidence of Adverse Events [Safety and Tolerability]

Description

Time Frame

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

Title

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)

Title

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)

Title

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 Measure Information:

Title

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

Time Frame

Baseline to 12 weeks (Period 1)

Title

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)

Title

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

Time Frame

Baseline to 24 weeks (Period 2)

Title

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)

Title

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)

Title

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

Time Frame

Baseline to 12 weeks (Period 1)

Title

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

Time Frame

Baseline to 24 weeks (Period 2)

Title

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

Time Frame

Baseline to 12 weeks (Period 1)

Title

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

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in DAS28-CRP

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in DAS28-CRP

Time Frame

Baseline to 36 weeks (Period 3)

Title

Change in DAS28-CRP

Time Frame

Baseline to 48 weeks (Period 3)

Title

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

Time Frame

Baseline to 12 weeks (Period 1)

Title

Change in HAQ-DI score

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in HAQ-DI score

Time Frame

Baseline to 36 weeks (Period 3)

Title

Change in HAQ-DI score

Time Frame

Baseline to 48 weeks (Period 3)

Title

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

Time Frame

Baseline to 12 weeks (Period 1)

Title

Change in SF-36 physical component score

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in SF-36 physical component score

Time Frame

Baseline to 36 weeks (Period 3)

Title

Change in SF-36 physical component score

Time Frame

Baseline to 48 weeks (Period 3)

Title

Change in SF-36 mental component score

Time Frame

Baseline to 12 weeks (Period 1)

Title

Change in SF-36 mental component score

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in SF-36 mental component score

Time Frame

Baseline to 36 weeks (Period 3)

Title

Change in SF-36 mental component score

Time Frame

Baseline to 48 weeks (Period 3)

Title

Change in SF-36 domain score

Time Frame

Baseline to 12 weeks (Period 1)

Title

Change in SF-36 domain score

Time Frame

Baseline to 24 weeks (Period 2)

Title

Change in SF-36 domain score

Time Frame

Baseline to 36 weeks (Period 3)

Title

Change in SF-36 domain score

Time Frame

Baseline to 48 weeks (Period 3)

Title

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

Description

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

Time Frame

Through 48 weeks

Title

To evaluate the participants' perception of therapy and sensation

Description

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

Time Frame

Through 48 weeks

Title

Evaluate device performance as assessed by tabulation of device deficiencies

Time Frame

Through 48 weeks

Title

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

Time Frame

week 12 to week 24

Title

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

Title

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

Time Frame

week 12 to week 24

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Operations Director

Phone

+1 877 613 9001

clinical@galvani.bio

Facility Information:

Facility Name

Pinnacle Research Group, LLC

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207

Country

United States

Individual Site Status

Withdrawn

Facility Name

Medvin Research - Covina

City

Covina

State/Province

California

ZIP/Postal Code

91722

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

626-869-5730

Info@medvinresearch.com

First Name & Middle Initial & Last Name & Degree

Samy Metyas, MD

Facility Name

Medvin Research - Whittier

City

Whittier

State/Province

California

ZIP/Postal Code

90602

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

562-758-6600

Info@medvinresearch.com

First Name & Middle Initial & Last Name & Degree

Tien-I Karleen Su, MD

Facility Name

The Osteoporosis & Clinical Trials Center

City

Hagerstown

State/Province

Maryland

ZIP/Postal Code

21740

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

301-791-6680

arthritis@rheumdocs.com

First Name & Middle Initial & Last Name & Degree

Mary Howell, MD

Facility Name

NYU Langone

City

Brooklyn

State/Province

New York

ZIP/Postal Code

11201

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Galvani Operations Director

Phone

877-613-9001

clinical@galvani.bio

First Name & Middle Initial & Last Name & Degree

David Goddard, MD

Facility Name

Altoona Center for Clinical Research

City

Altoona

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

800-924-7790

First Name & Middle Initial & Last Name & Degree

Alan Kivitz, MD

Facility Name

Arthritis & Rheumatology Institute

City

Allen

State/Province

Texas

ZIP/Postal Code

75013

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

972-798-8553

First Name & Middle Initial & Last Name & Degree

Megha Patel-Banker, MD

Facility Name

St. David's Healthcare

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

SDH Office of Research; Research Dept

Phone

512-544-8070

Krishna.Saini@stdavids.com

First Name & Middle Initial & Last Name & Degree

Robert J. Koval, MD

Facility Name

Tekton Research

City

Austin

State/Province

Texas

ZIP/Postal Code

78745

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

Phone

512-388-5717

trials@tektonresearch.com

First Name & Middle Initial & Last Name & Degree

Paul Pickrell, MD

Facility Name

Metroplex Clinical Research Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Recruitment Specialist

Phone

214-424-0405

info@mcrcdallas.com

First Name & Middle Initial & Last Name & Degree

Roy Fleischmann, MD

Facility Name

Southwest Rheumatology Research

City

Mesquite

State/Province

Texas

ZIP/Postal Code

75150

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordiinator

Phone

972-288-2600

jointpain@swrr.net

First Name & Middle Initial & Last Name & Degree

Atul Singhal, MD

Facility Name

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

City

Amsterdam

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Study Coordinator

First Name & Middle Initial & Last Name & Degree

Sander Tas, MD

12. IPD Sharing Statement

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Splenic Stimulation for RA

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