Testing N-Acetyl Cysteine for Gulf War Veterans with Chronic Symptoms

Mechanisms of Oxidative Stress During N-Acetyl Cysteine (NAC) Supplementation in Veterans With Gulf War Illness (GWI)

This study is testing if N-Acetyl Cysteine can help Gulf War veterans with chronic symptoms like fatigue and pain by improving their body's ability to fight stress and boost energy levels.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 47 Years to 70 Years
• Sex: All
• Sponsor: Nova Southeastern University (Academic / other)
• Locations: 7 sites (Palo Alto, California and 6 other locations)
• Trial ID: NCT04987775 on ClinicalTrials.gov

What this trial studies

This mechanistic study investigates the effects of N-Acetyl Cysteine (NAC) on chronic oxidative stress and antioxidant depletion in Gulf War veterans suffering from Gulf War Illness (GWI). Participants will undergo blood specimen collection and neuroimaging to assess changes in serum glutathione levels and oxidative stress in the central nervous system compared to a placebo group. The study aims to understand whether NAC can improve mitochondrial function and alleviate symptoms associated with GWI, which include fatigue, pain, and cognitive issues. By focusing on the biochemical mechanisms involved, this research seeks to provide insights into potential therapeutic interventions for affected veterans.

Who should consider this trial

Good fit: Ideal candidates are Gulf War veterans aged 47 to 70 who meet specific criteria for Gulf War Illness.

Not a fit: Patients with severe traumatic brain injury or untreated major depression with psychotic features may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new treatment option to alleviate symptoms of Gulf War Illness in veterans.

How similar studies have performed: While there is growing evidence regarding oxidative stress in GWI, this specific approach using NAC is novel and has not been extensively tested in this population.

Eligibility criteria

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 modified Kansas definition includes the following:

  1. Allowance of normal illness 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.
  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 or melancholic features (as determined by self-report and Hamilton Depression Inventory (Ham-D)), schizophrenia, bipolar disorder, delusional disorders, dementias of any type, or a history of central nervous system (CNS) disorders that may affect cognitive 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 other enclosed space (MRS substudy only)
* Presence of ferrous implanted medical devices or metal fragments or objects that are embedded under the skin (MRS substudy only)
* 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.
* Chronic active infections such as HIV, Hepatitis B Virus (HBV), and Hepatitis C Virus (HCV) (self-report or antibody titer)
* Renal disease (self-report or laboratory results: renal insufficiency with serum creatinine \> 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 with HgbA1c \> 7.5 will be reviewed and judged by the PI or delegate; if potential participant 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 to screening
* Currently have exclusionary diagnoses that could reasonably explain the symptoms of their fatiguing illness and their severity
* Are scheduled for a surgery during the period of study participation or had surgery within 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 pegylated interferon, ribavirin, entecavir, tenofovir, or didanosine for more than 7 days within 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, or planning to participate in another interventional clinical trial of an investigational therapy during the course of this study
* Any herbal medicine within 30 days prior to consent and screening blood draw

Where this trial is running

Palo Alto, California and 6 other locations

• VA Palo Alto Health Care System War Related Illness and Injury Study Center — Palo Alto, California, United States (Recruiting)
• Nova Southeastern University — Fort Lauderdale, Florida, United States (Recruiting)
• Boston University Medical School — Boston, Massachusetts, United States (Active_not_recruiting)
• VA New Jersey Health Care System War Related Illness and Injury Study Center — East Orange, New Jersey, United States (Recruiting)
• Weill Cornell Medical College — New York, New York, United States (Active_not_recruiting)
• RTI International — Durham, North Carolina, United States (Active_not_recruiting)
• Michael E. DeBakey VA Medical Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Nancy Klimas, MD — Nova Southeastern Univeristy
• Study coordinator: Nancy Klimas, MD

Conditions Gulf War Syndrome; CNS Recovery; N-Acetyl Cysteine; Gulf War Illness; Placebo