Etanercept + Mifepristone for Gulf War Syndrome

(E/M Trial)

Recruiting at 1 trial location

Overseen By Amanpreet Cheema, PhD

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Nova Southeastern University

Must not be taking: Steroids, Immunosuppressants, Rivaroxaban, Licorice

Disqualifiers: Major depression, Schizophrenia, Bipolar, Alcoholism, others

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

Compensation: Varies

Number of Visits: 6

Duration: 13 weeks

20 Participants Needed

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.

Will I have to stop taking my current medications?

The trial requires stopping certain medications that affect immune function, like steroids or immunosuppressants. If you're on blood thinners like Warfarin or Apixaban, the dose will need to be adjusted. It's best to discuss your specific medications with the trial coordinator.

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 data supports the effectiveness of the drug Etanercept for treating Gulf War Syndrome?

Etanercept has been shown to be effective in treating chronic inflammatory diseases like rheumatoid arthritis and juvenile idiopathic arthritis, suggesting it may help with similar inflammatory conditions. ^{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 combination of Etanercept and Mifepristone safe for humans?

Etanercept has been shown to be generally safe in humans for conditions like rheumatoid arthritis, with minor side effects such as injection site reactions and mild infections. However, caution is advised as it may reactivate tuberculosis and there are concerns about a potential link to lymphoma. There is no specific safety data available for the combination of Etanercept and Mifepristone. ^{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}

How is the drug Etanercept + Mifepristone unique for treating Gulf War Syndrome?

Etanercept + Mifepristone is unique for treating Gulf War Syndrome because it combines Etanercept, a drug that blocks inflammation by targeting tumor necrosis factor (a protein involved in inflammation), with Mifepristone, which is known for its use in other conditions but not typically for inflammation. This combination may offer a novel approach to managing symptoms by addressing inflammation in a way that other treatments for Gulf War Syndrome do not. ^{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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etanercept 50 mg weekly for 12 weeks followed by mifepristone for 1 week

13 weeks

6 visits (in-person) at baseline, 6, 12, 13, 16, and 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Etanercept
• Mifepristone

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 United States, European Union, Canada for the following indications:

Approved in United States as Enbrel for:

• Moderate to Severe Rheumatoid Arthritis
• Moderate to Severe Polyarticular Juvenile Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Moderate to Severe Plaque Psoriasis

Approved in European Union as Enbrel for:

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

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+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Miami VA Healthcare System

Collaborator

Trials

18

Recruited

2,400+

Findings from Research

Etanercept is a fusion protein that acts as a soluble receptor for tumor necrosis factor (TNF), effectively used to treat various chronic inflammatory diseases in humans, such as rheumatoid arthritis and psoriasis.

To study its effects in mouse models, researchers developed a murine version of the soluble p75-TNF receptor, allowing for better understanding of its mechanism in conditions that mimic human granulomatous infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. Kim, HY., Renshaw-Gegg, LW., Balciunas, AM., et al.[2016]

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]

Etanercept has shown preliminary effectiveness in treating methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA), suggesting it could be a valuable option for patients who do not respond to standard treatments.

While most side effects of etanercept have been minor, two patients experienced a urticaria-like rash after injections, indicating that while generally safe, some individuals may have specific adverse reactions that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. Skyttä, E., Pohjankoski, H., Savolainen, A.[2017]

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]

Preliminary reports suggest that etanercept does not increase morbidity or mortality in patients with HIV, indicating it may be a safe option for managing symptoms associated with HIV/AIDS.

Etanercept may help alleviate symptoms such as aphthous ulcers, cachexia, and fatigue in HIV/AIDS patients, while also managing related rheumatic diseases, but further research is needed to confirm its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. Ting, PT., Koo, JY.[2015]

Etanercept is an effective and safe treatment for rheumatoid arthritis (RA), significantly reducing disease activity and preventing joint damage, and can be used alone or with methotrexate for enhanced effectiveness.

While generally safe, etanercept requires caution due to potential risks such as re-activating tuberculosis and concerns about lymphoma, and it is recommended for patients who have not responded to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept in arthritis. Scott, DL.[2015]

In a study of 22 patients with severe and refractory psoriasis, 96% showed significant improvement in their disease severity after 12 weeks of treatment with etanercept, and this improvement was maintained until week 24.

Etanercept was well tolerated by patients, with no significant adverse reactions reported, although the average time until relapse was approximately 2.27 months, indicating a need for further long-term safety and efficacy studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Refractory psoriasis treatment with etanercept]. Mahiques Santos, L., Martínez-Menchón, T., Sánchez Carazo, JL., et al.[2019]

Murine p75-Fc, a soluble TNF receptor protein, effectively inhibits TNF-induced IL-6 production in mice, with complete inhibition observed at doses of 5 and 15 mg/kg.

At a lower dose of 1.5 mg/kg, murine p75-Fc still significantly reduced IL-6 production, indicating its potential as a therapeutic agent in managing inflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic effects of the murine p75-Fc fusion protein in mice. Hu, YL., Kim, HY., Kohno, T., et al.[2016]

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]