TNF and Glucocorticoid Antagonist for GWI Associated Multi-symptom Disease Homeostasis Reset

• Status: Recruiting
• Trial end date: 2023-07-30
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nova Southeastern University
• Collaborators: Rochester General Hospital; RTI International
• Treatments: Etanercept; Glucocorticoids; Mifepristone

Criteria

Inclusion Criteria:

• 45-70 years old

• Male sex

• In good health by medical history prior to 1990

• Davidson Trauma scale score of 50 or higher

• Meets modified Kansas and CDC case definition criteria for Gulf War Illness. The modified Kansas definition, which includes the CDC criteria, includes the following:

1. Fatigue after exercise as predominant component (a history of exercise intolerance or exercise-induced worsening of symptoms)

2. Allowance for normal illnesses of aging, such as hypertension and diabetes, if the conditions are treated and are in demonstrable stable and normal ranges at the time of screening and assessment

3. Allowance of stable comorbid conditions such as PTSD (post traumatic stress disorder), MDD (major depressive disorder), and TBI (traumatic brain injury) that have not required hospitalization in the 5 years prior to recruitment. Severe TBI is excluded.

• Able to provide consent to study

• Protective titers for influenza and pneumococcal pneumonia, or updated vaccination for these infections

• Patients of childbearing potential must practice effective contraception during the study, and be willing to continue contraception for at least 6 months after intervention

• Agrees to participate in follow-up visits

Exclusion Criteria:

• Current treated or untreated major depression with psychotic or melancholic features, schizophrenia, bipolar disorder, delusional disorders, dementias of any type, and alcoholism or drug abuse (as determined by self-report, Structured Clinical Interview for DSM disorders (SAGE-SR), and Ham-D)

• Known allergy to mifepristone, misoprostol, or medicines that contain misoprostol, such as Cytotec or Arthrotec

• Current heavy alcohol or tobacco use (self-report). Alcohol consumption not to exceed approximately 15 drinks per week (with a drink defined as 12 oz. beer, 5oz. wine, or 1.5 oz. distilled spirits) and tobacco use not exceed 20 cigarettes (or equivalent) per day.

• Current organ failure (as determined by metabolic panel and self-report)

• Current treated or untreated rheumatologic and inflammatory disorders, as determined by medical diagnosis of one or more of the following: osteoarthritis, rheumatoid arthritis (RA), lupus, spondyloarthropathies -- ankylosing spondylitis (AS) and psoriatic arthritis (PsA), Sjogren's syndrome, gout, scleroderma, infectious arthritis, and polymyalgia rheumatic

• Chronic active infections such as HIV, hepatitis B, and hepatitis C (as determined by antibody tests)

• History of organ transplant (self-report)

• Current primary sleep disorders such as insomnias, sleep related breathing disorders, etc. (self-report)

• History of tuberculosis exposure (determined by QuantiFERON-TB® positivity)

• Any allergic disease (self-report) such as food/drug allergies and allergic asthma

• Use of medications that could affect immune function (e.g., steroids, immunosuppressants) or limit the interpretation of the exercise challenge (e.g., beta blockers) (self-report)

• Renal insufficiency with serum creatinine > 2.0 mg/dL

• Hepatic insufficiency (bilirubin >2.5mg/dL or transaminases >5x the ULN) Patients with Gilberts syndrome are eligible for the study if other liver function tests are normal, regardless of bilirubin level

• Currently have no exclusionary diagnoses that could reasonably explain the symptoms of their fatiguing illness and their severity, using the exclusion criteria best described in the Ambiguities in case definition paper for Chronic Fatigue Syndrome (CFS), as described in detail in Reeves, et all 2003, which clarifies exclusionary conditions.

• Are scheduled for a surgery within 24 weeks of study enrollment.

Prohibited concomitant or prior therapies:

• Immunosuppressant drugs, including glucocorticoid taper, topical/inhaled glucocorticoids

• Currently on dialysis

• Recipient of bone marrow or organ transplant

• Previous or current treatment with angiogenic growth factors, cytokines, gene or stem cell therapy

• Participating in another interventional clinical trial of an investigational therapy within 8 weeks prior to consent to participate in this study, or planning to participate in another interventional clinical trial of an investigational therapy within 26 weeks after consent to participate in this study

• Any herbal medicine

• Blood thinners