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

Inclusion Criteria:

1. 45-70 years old,
2. Male sex,
3. In good health by medical history prior to 1990
4. Meets modified Kansas and CDC case definition criteria for Gulf War Illness. Original Kansas criteria and CDC case definitions, including their exclusionary conditions. 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, MDD, and TBI that have not required hospitalization in the 5 years prior to recruitment. Severe TBI is excluded.
5. Able to provide consent to study,
6. Subjects of childbearing potential must practice effective contraception during the study, and be willing to continue contraception for at least 6 months after intervention.
7. Agrees to participate in follow-up visits.

Exclusion Criteria:

1. 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, SAGE-SR, and Ham-D)
2. Known allergy to mifepristone, misoprostol, or medicines that contain misoprostol, such as Cytotec or Arthrotec.
3. 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, 5 oz wine, or 1.5 oz distilled spirits) and tobacco use not to exceed 20 cigarettes (or equivalent) per day.
4. Current organ failure (as determined by metabolic panel and self-report)
5. 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
6. Chronic active infections such as HIV, hepatitis B, and hepatitis C (as determined by antibody tests
7. History of organ transplant (self-report)
8. Current untreated primary sleep disorders such as insomnias, sleep related breathing disorders, etc. (self-report)
9. History of tuberculosis exposure (determined by QuantiFERON-TB® positivity)
10. Use of medications that could affect immune function (e.g., steroids, immunosuppressants) or limit the interpretation of the exercise challenge (self- report)
11. Renal disease (self-report; laboratory results: renal insufficiency with serum creatinine \> 2.0 mg/dL or eGFR \< 44; or currently on renal dialysis).
12. Hepatic insufficiency (bilirubin \>2.5mg/dL or transaminases \>5x the ULN) Subjects with Gilberts syndrome are eligible for the study if other liver function tests are normal, regardless of bilirubin level.
13. 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) which clarifies exclusionary conditions.
14. Are scheduled for surgery within 24 weeks of study enrollment.
15. Cushing's disease or salivary cortisol level greater than 0.812 ug/dL.
16. QT prolongation, as evidenced by medical history (self-report) or ECG at screening.
17. Uncontrolled diabetes (A1c\>7.5).

Prohibited concomitant or prior therapies:

1. Immunosuppressant drugs, including glucocorticoid taper, topical/inhaled glucocorticoids
2. Currently on dialysis
3. Recipient of bone marrow or organ transplant
4. Previous or current treatment with angiogenic growth factors, cytokines, gene or stem cell therapy
5. 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
6. Any herbal medicine that contains licorice root.
7. Selective Blood thinners:

   * Only Apixaban and Warfarin will be included. Rivaroxaban cannot be included as there are higher drug to drug interactions as well as Apixaban 2.5 mg BID.
   * If a participant is on Warfarin, a baseline INR will be obtained, the Warfarin dose will be reduced and an INR will be rechecked 48-72 hours after starting Mifepristone.
   * If a participant is on Apixaban, the dose must be reduced by 50%.
   * Please note that if participants are taking anticoagulants, there is a potential interaction that could lead to possible increased on risk of bleeding and will require more frequent monitoring by the Coordinator.