Splenic Stimulation for Rheumatoid Arthritis

Recruiting at 11 trial locations

Overseen By Operations Director

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Galvani Bioelectronics

Must be taking: Conventional DMARDs

Disqualifiers: Psychiatric disease, Substance abuse, Tuberculosis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions a 'washout period' for previously used biological DMARDs or JAK inhibitors. This means you might need to stop these specific medications for a certain time before starting the trial.

What data supports the effectiveness of the treatment involving Splenic Stimulation for Rheumatoid Arthritis?

Research shows that targeting the immune system can be effective in treating rheumatoid arthritis, as seen with therapies that inhibit specific immune components like TNF-alpha. Advances in biotechnology and immunomodulatory strategies have shown promise in managing autoimmune diseases, suggesting that novel approaches like splenic nerve stimulation could potentially offer benefits by modulating immune responses. ^{1 2 3 4 5}

Is splenic stimulation therapy safe for humans?

The safety of biologic therapies, which are similar to splenic stimulation, has been studied extensively, showing specific risks like infections and infusion reactions. Before starting such treatments, screening for infections like tuberculosis is standard to ensure safety. ^{4 6 7 8 9}

How is the Galvani System treatment different from other rheumatoid arthritis treatments?

The Galvani System is unique because it uses bioelectronic medicine to stimulate the splenic nerve, targeting the body's inflammatory reflex to reduce inflammation without the use of drugs. This approach is different from traditional treatments that rely on systemic medications, offering a non-drug alternative for managing rheumatoid arthritis. ^{1 10 11 12 13}

Eligibility Criteria

This trial is for adults aged 22-75 with active rheumatoid arthritis (RA) who haven't responded well to at least two biologic DMARDs or JAK inhibitors, including a TNF inhibitor. They must have stopped previous RA treatments for a specific time before joining. People with implanted electrical devices, significant psychiatric issues, substance abuse problems, certain infections like COVID-19 or tuberculosis, HIV, hepatitis B/C, or those who've had vagotomy or splenectomy can't join.

Inclusion Criteria

I am on standard doses of synthetic drugs for my autoimmune disease.

I have not improved after trying at least two types of advanced arthritis medication.

I have stopped my previous biologic or JAK inhibitor treatments for enough time.

Exclusion Criteria

I have tuberculosis, whether active or not.

I have HIV or current/past hepatitis B or C.

You have a medical device implanted in your body that emits electrical signals, like a pacemaker or implantable defibrillator.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Control Trial

Participants receive either active stimulation or sham-stimulation for 12 weeks

12 weeks

Open Label

Participants who responded to stimulation continue on stimulation; others receive a market-approved RA drug for 12 weeks

12 weeks

Treat-to-target

Participants treated with dual therapy (stimulation and RA drug) for up to 24 weeks

24 weeks

Long-term Follow-up

Long-term safety follow-up for all participants for 5 years, with possible stimulation and standard of care therapies

5 years

Treatment Details

Interventions

• Baricitinib
• Galvani System

Trial Overview The study tests the Galvani System's safety and effects on stimulating the splenic neurovascular bundle in RA patients. It includes an initial randomized control phase where some get real stimulation and others sham (fake) treatment; followed by open label and treat-to-target periods; ending with long-term follow-up to assess outcomes.

Participant Groups

Group I: RA drug combined with active stimulation, Period 3 Experimental Treatment 3 Interventions

Participants on baricitinib during Period 2 will have active stimulation added for 24 weeks

Group II: Open label active stimulation, Period 2 Experimental Treatment 2 Interventions

Open label active stimulation for 12 additional weeks

Group III: Open label RA Drug, Period 2 Experimental Treatment 2 Interventions

Open label drug treatment with baricitinib for 12 weeks

Group IV: Long-term Follow-up, Period 4 Experimental Treatment 2 Interventions

Standard of care treatments with or without stimulation

Group V: Active stimulation combined with RA drug, Period 3 Experimental Treatment 3 Interventions

Participants on active stimulation during Period 2 will have baricitinib added for 24 weeks

Group VI: Active Stimulation; Period 1 Experimental Treatment 2 Interventions

Active stimulation for 12 weeks

Group VII: Sham Stimulation; Period 1 Placebo Group 2 Interventions

Sham stimulation for 12 weeks

Who Is Running the Clinical Trial?

Galvani Bioelectronics

Lead Sponsor

Trials

3

Recruited

50+

NAMSA

Collaborator

Trials

55

Recruited

21,500+

Q2 Solutions

Industry Sponsor

Trials

15

Recruited

1,600+

Findings from Research

Nanotechnology has the potential to significantly enhance the treatment of autoimmune diseases by improving the delivery of biological immunomodulatory agents, addressing common issues like inadequate targeting and systemic side effects.

This review highlights various nanomedicine strategies that could induce immunosuppression and promote immunological tolerance, offering new hope for conditions such as psoriasis, rheumatoid arthritis, and multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction. Gharagozloo, M., Majewski, S., Foldvari, M.[2022]

Monoclonal antibodies targeting TNF-alpha have shown significant anti-inflammatory effects in rheumatoid arthritis (RA) patients, but their effectiveness may be limited by the development of antibodies against the treatment itself.

New treatment strategies, such as oral collagen and potential gene therapy, are being explored to regulate autoimmune activity in RA, which could lead to innovative approaches in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapies: a novel approach to the treatment of autoimmune disease. Fox, DA.[2019]

Immunomodulatory nanoparticles have the potential to treat rheumatoid arthritis (RA) by delivering self-antigens and immunomodulators, which may help the immune system learn to tolerate its own tissues instead of attacking them.

Recent advances in these nano-preparations include their ability to simulate apoptotic cells and act as artificial antigen-presenting cells, offering promising new avenues for developing immunotherapies for RA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory nano-preparations for rheumatoid arthritis. Li, C., Han, Y., Luo, X., et al.[2022]

Recent advancements in immunomodulatory therapies for rheumatoid arthritis (RA) have been driven by a better understanding of the disease's immune mechanisms and the development of specific inhibitors, leading to promising new treatment options.

Monoclonal antibodies and other biopharmaceuticals targeting key components of the immune response, such as proinflammatory cytokines like TNF-alpha, have shown significant efficacy in clinical trials, suggesting a bright future for more effective and safer RA treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of immunomodulatory intervention in rheumatoid arthritis. Kavanaugh, A.[2019]

Rheumatoid Arthritis involves a complex immune response where activated T-lymphocytes and macrophages infiltrate joint tissues, leading to the production of inflammatory mediators that contribute to joint damage.

Leukapheresis, a procedure that removes white blood cells, can provide temporary clinical improvement in patients with classic rheumatoid arthritis by disrupting the traffic of T-lymphocytes, although the disease shows significant heterogeneity among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis. Wilder, RL., Malone, DG., Yarboro, CH., et al.[2019]

Biological therapies for autoimmune rheumatic diseases, such as rheumatoid arthritis and spondyloarthritides, have improved treatment outcomes but come with potential safety concerns, including risks of infections, infusion reactions, and other serious side effects.

The Brazilian Society of Rheumatology conducted a comprehensive review of safety data over the last two decades, categorizing risks by drug class and providing guidelines for safe use, including considerations for pregnancy and lactation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides]. Mota, LM., Cruz, BA., Brenol, CV., et al.[2017]

Combination therapy using two or more biologic agents may provide better treatment outcomes for rheumatoid arthritis (RA) compared to single-agent therapies, as suggested by animal model data showing synergistic effects.

While there are potential risks associated with combination biologic therapies, such as increased toxicity and infection risk, careful clinical trials in patients with earlier stages of RA could lead to effective treatments with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future use of biologic therapies in combination for the treatment of rheumatoid arthritis. Strand, V.[2005]

Biologics are effective treatments for rheumatoid arthritis (RA) and spondylarthritis (SpA), targeting specific inflammatory pathways and recommended for patients who do not respond to traditional medications.

While biologics can significantly improve disease outcomes, they carry a risk of infections, necessitating screening for conditions like latent tuberculosis and hepatitis B before treatment initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of rheumatoid arthritis and spondylarthritis with biologics]. Fiehn, C.[2022]

Biological treatments have significantly improved the management of rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis, highlighting their efficacy in these conditions.

For gene therapy to be a viable alternative, it must prove to be safer and more beneficial for patients compared to existing biologicals, while also being economically feasible and accessible to global patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for arthritis--where do we stand? Chernajovsky, Y.[2018]

The review highlights the potential of bioelectronic medicine, specifically the 'inflammatory reflex,' as a nonpharmacological treatment for diseases, focusing on its application in rheumatoid arthritis (RA).

A next-generation implanted pulse generator utilizing integrated electrodes is currently being evaluated in a clinical study for patients with drug-refractory RA, showcasing the innovative approach of targeted neurostimulation in managing chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing the Inflammatory Reflex for the Treatment of Inflammation-Mediated Diseases. Levine, YA., Faltys, M., Chernoff, D.[2022]

Vibrotactile treatment applied to the cymba concha of the ear significantly reduced levels of inflammatory cytokines TNF, IL-1β, and IL-6 in healthy subjects, with effects lasting up to 24 hours.

In patients with rheumatoid arthritis, this treatment led to a significant decrease in disease activity scores (DAS28-CRP) two days post-treatment, with sustained improvements observed even seven days later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. Addorisio, ME., Imperato, GH., de Vos, AF., et al.[2022]

Vagus nerve stimulation (VNS) has shown promise in reducing inflammation and pain in various musculoskeletal diseases, including rheumatoid arthritis, with pilot studies indicating significant decreases in disease activity.

Both invasive and non-invasive VNS methods have been associated with benefits in conditions like Sjogren's syndrome and fibromyalgia, but further randomized controlled trials are needed to confirm these findings and determine optimal treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in musculoskeletal diseases. Courties, A., Berenbaum, F., Sellam, J.[2021]

The study developed a pH-responsive dual pulse multiparticulate system for ketoprofen, which is designed to provide targeted drug release for rheumatoid arthritis relief, particularly during nighttime and early morning when symptoms are often worse.

In vitro tests showed that the pellets successfully released ketoprofen in a controlled manner, with a lag time of 2 and 5 hours, simulating the gastrointestinal pH conditions, indicating potential for effective symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

pH-responsive dual pulse multiparticulate dosage form for treatment of rheumatoid arthritis. Lotlikar, V., Kedar, U., Shidhaye, S., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Biological therapies: a novel approach to the treatment of autoimmune disease. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Immunomodulatory nano-preparations for rheumatoid arthritis. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

An overview of immunomodulatory intervention in rheumatoid arthritis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis. [2019]

6. Brazil pubmed.ncbi.nlm.nih.gov

[Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides]. [2017]

7. Canada pubmed.ncbi.nlm.nih.gov

The future use of biologic therapies in combination for the treatment of rheumatoid arthritis. [2005]

8. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of rheumatoid arthritis and spondylarthritis with biologics]. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Gene therapy for arthritis--where do we stand? [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Harnessing the Inflammatory Reflex for the Treatment of Inflammation-Mediated Diseases. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear. [2022]

12. France pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in musculoskeletal diseases. [2021]

13. England pubmed.ncbi.nlm.nih.gov

pH-responsive dual pulse multiparticulate dosage form for treatment of rheumatoid arthritis. [2013]