GWICTIC: NAC Mechanistic Study in Gulf War Veterans

NCT04987775 | Recruiting Early Phase 1 DMC

• 1 other identifier: GWICTIC-NAC
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 7

Brief Summary

This mechanistic study will test if NAC affects chronic oxidative stress and depletion of antioxidants in GWI participants. Blood specimen collection and neuroimaging will be used to determine whether NAC affects serum glutathione (GSH) concentration and oxidative stress in the CNS when compared to placebo.

Conditions

Gulf War Syndrome

Keywords

CNS Recovery; N-Acetyl Cysteine (NAC); Gulf War Illness; Placebo

Outcome Measures

Primary Outcomes (1)

• Assess glutathione levels

  Change in glutathione levels after NAC supplementation compared to placebo in participants with gulf war illness (GWI)

  Baseline to 8 weeks

Secondary Outcomes (2)

• Change in glutathione levels

  Baseline to 8 Weeks

• Change in number of participants with treatment-related adverse events

  Baseline to 16 Weeks

Study Arms (2)

N-Acetyl Cysteine (NAC)

ACTIVE COMPARATOR

Participants who are randomized to the intervention arm will receive N-Acetyl-L-Cysteine (Free-Form/NAC) 900mg two times a day for 8 weeks after the initiation of the first dose of study drug.

Drug: N-Acetyl Cysteine

Placebo

PLACEBO COMPARATOR

Participants who are randomized to the placebo arm will take matching placebo two times a day for 8 weeks after the initiation of the first dose of study drug.

Drug: Placebo

Interventions

N-Acetyl Cysteine DRUG

900mg 2x daily

Also known as: NAC

N-Acetyl Cysteine (NAC)

Placebo DRUG

Matching placebo bid

Also known as: NAC Placebo

Placebo

Eligibility Criteria

• Age: 47 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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)
• 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
• 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

Sponsors & Collaborators

• Nova Southeastern University: lead
• RTI International: collaborator
• Boston University: collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (7)

VA Palo Alto Health Care System War Related Illness and Injury Study Center

Palo Alto, California, 94304, United States

RECRUITING

Nova Southeastern University

Fort Lauderdale, Florida, 33314, United States

RECRUITING

Boston University Medical School

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

VA New Jersey Health Care System War Related Illness and Injury Study Center

East Orange, New Jersey, 07018, United States

RECRUITING

Weill Cornell Medical College

New York, New York, 10021, United States

ACTIVE NOT RECRUITING

RTI International

Durham, North Carolina, 27709, United States

ACTIVE NOT RECRUITING

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Persian Gulf Syndrome

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Occupational Diseases; War-Related Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Nancy Klimas, MD

  Nova Southeastern Univeristy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy Klimas, MD

CONTACT

9542622855; nklimas@nova.edu

Karen Kesler, PhD

CONTACT

kkelser@rti.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants enrolled will be randomized into one of two arms: NAC or Placebo.

Study Record Dates

• First Submitted: June 7, 2021
• First Posted: August 3, 2021
• Study Start: November 30, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)