Etanercept + Mifepristone for Gulf War Syndrome

(E/M Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Nancy Klimas, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Nova Southeastern University

No Placebo Group

Trial Summary

What is the purpose of this trial?

Gulf War Illness is a condition that affects multiple major organ systems, resulting in a diverse array of symptoms that include debilitating fatigue, memory and cognition difficulties, headaches, sleep disturbances, gastrointestinal problems, skin rashes, and musculoskeletal/joint pain. This phase I single-site, open-label two-arm study will assess the safety and mechanistic efficacy of a sequential etanercept-mifepristone intervention for Gulf War Illness. The results of this phase I study will be compared to those from an existing short-duration study to identify the optimal duration and dosage for use in a future phase II study.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but certain medications are prohibited. You cannot take immunosuppressants, glucocorticoids, or participate in another clinical trial. If you're on Warfarin or Apixaban, dosage adjustments are required. Herbal medicines with licorice root are also not allowed.

What data supports the idea that Etanercept + Mifepristone for Gulf War Syndrome is an effective drug?

The available research shows that Etanercept has been effective in treating other inflammatory conditions like rheumatoid arthritis and juvenile idiopathic arthritis. However, there is no specific data provided about its effectiveness for Gulf War Syndrome. The studies mention improvements in conditions like rheumatoid arthritis when Etanercept is used, but they do not directly address Gulf War Syndrome or the combination with Mifepristone. Therefore, while Etanercept is effective for some inflammatory diseases, we don't have direct evidence from the provided information about its effectiveness for Gulf War Syndrome. ^{1 2 3 4 5}

What safety data exists for Etanercept and Mifepristone treatment?

Etanercept, a TNF receptor fusion protein, has been shown to be effective and generally safe in treating various inflammatory conditions like rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, and ankylosing spondylitis. Common side effects include injection site reactions and upper respiratory infections, with rare cases of urticaria-like rash. Caution is advised due to potential risks like tuberculosis reactivation and a possible link to lymphoma. There is limited data on the use of Etanercept in HIV/AIDS patients. No specific safety data for the combination of Etanercept and Mifepristone for Gulf War Syndrome is available in the provided research. ^{1 2 3 6 7}

Is the drug Etanercept a promising treatment for Gulf War Syndrome?

Etanercept is a promising drug because it has been effective in treating various chronic inflammatory diseases like rheumatoid arthritis and psoriasis. It works by blocking inflammatory responses, which could be beneficial for conditions like Gulf War Syndrome that may involve inflammation. ^{1 3 6 8 9}

Research Team

Nancy Klimas, MD

Principal Investigator

Miami VA Healthcare System

Eligibility Criteria

This trial is for male individuals aged 45-70 with Gulf War Illness, who were in good health before 1990 and meet specific illness criteria. They must not have severe comorbid conditions or a history of heavy alcohol/tobacco use. Participants should not have certain chronic infections, organ failure, or be on excluded medications like immunosuppressants.

Inclusion Criteria

I am between 45 and 70 years old.

I was in good health before 1990 according to my medical records.

My PTSD, depression, or brain injury is stable and hasn't needed hospital care in the last 5 years.

Exclusion Criteria

I have a diagnosed condition like arthritis, lupus, or another inflammatory disorder.

My fatigue is not explained by any other diagnosed conditions.

I have not used any treatments that are not allowed in this study.

Treatment Details

Interventions

• Etanercept (Monoclonal Antibodies)
• Mifepristone (Glucocorticoid Antagonist)

Trial Overview The study tests the safety and efficacy of Etanercept followed by Mifepristone to treat symptoms of Gulf War Illness. It's an early-phase trial comparing results with a previous study to find the best dosage and duration for future research.

Participant Groups

Group I: Mifepristone 600 mg Experimental Treatment 2 Interventions

All participants will receive etanercept 50 mg weekly for 12 weeks. After completion of the etanercept course, participants will be randomized between two Arms of mifepristone. Participants randomized to Arm 2 will receive one week of mifepristone at 600 mg (2x300 mg) daily.

Group II: Mifepristone 300 mg Experimental Treatment 2 Interventions

All participants will receive etanercept 50 mg weekly for 12 weeks. After completion of the etanercept course, participants will be randomized between two Arms of mifepristone. Participants randomized to Arm 1 will receive one week of mifepristone at 300 mg daily.

Etanercept is already approved in Canada for the following indications:

Approved in Canada as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Nova Southeastern University

Lead Sponsor

Trials

103

Recruited

12,000+

Dr. George L. Hanbury II

Nova Southeastern University

Chief Executive Officer since 2011

PhD in Higher Education Administration from Nova Southeastern University

Dr. Gary S. Margules

Nova Southeastern University

Chief Medical Officer since 2010

MD from University of Miami

RTI International

Collaborator

Trials

201

Recruited

942,000+

Dr. Anuja Purohit

RTI International

Chief Medical Officer

MD from Duke University School of Medicine

Tim J. Gabel

RTI International

Chief Executive Officer since 2022

Adjunct appointments at University of Wyoming and UNC Gillings School of Global Public Health

Miami VA Healthcare System

Collaborator

Trials

18

Recruited

2,400+

Findings from Research

In a randomized, double-blind, placebo-controlled trial involving 234 patients with active rheumatoid arthritis, etanercept demonstrated significant improvements in disease activity over 6 months, with 59% of patients achieving a 20% improvement compared to only 11% in the placebo group.

Etanercept was well tolerated and showed a dose-dependent effect, with no dose-limiting toxic effects, confirming its safety and efficacy as a treatment for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Moreland, LW., Schiff, MH., Baumgartner, SW., et al.[2022]

In a 24-week study involving 89 patients with rheumatoid arthritis who were not responding adequately to methotrexate alone, the addition of etanercept significantly improved clinical outcomes, with 71% of patients achieving a 20% improvement in disease activity compared to only 27% in the placebo group.

The combination therapy was safe and well tolerated, with only mild injection-site reactions reported, indicating that etanercept can be a beneficial addition to methotrexate for patients with persistent disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. Weinblatt, ME., Kremer, JM., Bankhurst, AD., et al.[2022]

T0001, a new recombinant fusion protein, was found to be safe and well-tolerated in a first-in-human trial involving 56 healthy Chinese volunteers, with no serious adverse events reported.

The pharmacokinetics of T0001 showed a slow absorption and elimination rate, with increasing plasma concentrations of TNFα after administration, although the study could not confirm linear pharmacokinetics across the tested doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and immunogenicity of T0001, a newly developed anti-TNFα fusion protein, in healthy volunteers. Wang, Y., Liu, C., Chen, S., et al.[2018]

References

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

Construction and purification of the murine p75-murine IgG1 fusion protein. [2016]

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

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. [2017]

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

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and immunogenicity of T0001, a newly developed anti-TNFα fusion protein, in healthy volunteers. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. [2015]

7. India pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. [2015]

8. Spain pubmed.ncbi.nlm.nih.gov

[Refractory psoriasis treatment with etanercept]. [2019]

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

Pharmacodynamic effects of the murine p75-Fc fusion protein in mice. [2016]