GWICTIC: NAC Mechanistic Study in Gulf War Veterans

Inclusion Criteria:

• 47 to 70 years

• Served in the Gulf War Theater for any period between August 1990 and July 1991.

• Meets modified Kansas case definition criteria for Gulf War Illness. The modifiedKansas definition includes the following:

1. Allowance of normal illness of aging, such as hypertension and diabetes, if theconditions are treated and are in demonstrable stable and normal ranges at thetime of screening and assessment.

2. Allowance of stable comorbid conditions such as Post Traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and mild Traumatic Brain Injury (mTBI)that have not required hospitalization in the 2 years prior to recruitment.Severe TBI is excluded.

• Able to provide written consent to the study

• Agrees to participate in follow-up visits.

Exclusion Criteria:

• Self-report of current treated or untreated major depression with psychotic ormelancholic features (as determined by self-report and Hamilton Depression Inventory (Ham-D)), schizophrenia, bipolar disorder, delusional disorders, dementias of anytype, or a history of central nervous system (CNS) disorders that may affectcognitive function (e.g., epilepsy, stroke, brain tumor, multiple sclerosis,Parkinson's Disease, Alzheimer's disease), or alcoholism or drug abuse

• Severe claustrophobia or serious difficulty being in an MRI scanner or otherenclosed space (MRS substudy only)

• Presence of ferrous implanted medical devices or metal fragments or objects that areembedded under the skin (MRS substudy only)

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

• Chronic active infections such as HIV, Hepatitis B Virus (HBV), and Hepatitis CVirus (HCV) (self-report or antibody titer)

• Renal disease (self-report or laboratory results: renal insufficiency with serumcreatinine > 2.0 mg/dL)

• Liver disease (self-report or laboratory results: hepatic insufficiency (bilirubin >2.5mg/dL or transaminases > 3 times the upper limits of normal)

• Uncontrolled diabetes (HgbA1c > 7.5) without adequate medical care. Individuals withHgbA1c > 7.5 will be reviewed and judged by the PI or delegate; if potentialparticipant has adequate medical care to manage diabetes, enrollment is allowed;otherwise HgbA1c > 7.5 is exclusionary

• Diagnosed vascular disease (including congestive heart failure)

• Diagnosed bleeding disorders or use of blood-thinning medications

• Receipt of stavudine or didanosine for more than 7 days within 30 days prior toscreening

• Currently have exclusionary diagnoses that could reasonably explain the symptoms oftheir fatiguing illness and their severity

• Are scheduled for a surgery during the period of study participation or had surgerywithin 6 weeks prior to screening

• Pregnant (women only)

Prohibited Concomitant or Prior Therapies

• Currently on dialysis

• Previous or current receipt of any antiviral medication, such as pegylatedinterferon, ribavirin, entecavir, tenofovir, or didanosine for more than 7 dayswithin 30 days prior to screening

• Participating in another interventional (including social-behavioral therapy)clinical trial of an investigational therapy within 6 weeks prior to consent, orplanning to participate in another interventional clinical trial of aninvestigational therapy during the course of this study

• Any herbal medicine within 30 days prior to consent and screening blood draw