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.
During the 1990-91 Gulf War (GW), military personnel were exposed to numerous chemical and environmental agents during deployment including spraying of pesticides, petroleum combustion products, and nerve gas. Exposure to these chemical and environmental agents can damage cell function and more specifically, mitochondrial function, which negatively affects energy production and can lead to oxidative stress and neuroinflammation. Animal models using similar exposures have documented this in the central nervous system (CNS) compartment. This disruption in mitochondrial function and energy production is likely tied to resulting symptoms of Gulf War Illness (GWI) including fatigue, headaches, joint and muscle pain, gastrointestinal and sleep disturbances, neurologic and neuropsychological symptoms, respiratory issues, and cardiovascular problems. The Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC) plans to evaluate N-Acetyl Cysteine (NAC) as a promising approach to help the CNS recover from chronic oxidative stress and depletion of antioxidants. The Congressionally Directed Medical Research Program's (CDMRP's) two Gulf War Illness Consortiums (GWICs) and others have added to the growing evidence of the role of CNS oxidative stress and neuroinflammation in symptoms of GWI, yet there is little definitive work on the delivery of antioxidants to the CNS environment. In this mechanistic study, we aim to determine if NAC has the ability to target mitochondrial dysfunction and reverse oxidative stress in the CNS. Based on our early experiences with antioxidants in GWI and other complex disease states along with the proven record of NAC in reducing glutathione (GSH) deficits, it is possible that this antioxidant will help to restore mitochondrial function and provide a more targeted approach to improve outcomes in Veterans with GWI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
170
900mg 2x daily
Matching placebo bid
VA Palo Alto Health Care System War Related Illness and Injury Study Center
Palo Alto, California, United States
RECRUITINGNova Southeastern University
Fort Lauderdale, Florida, United States
RECRUITINGBoston University Medical School
Assess glutathione levels
Change in glutathione levels after NAC supplementation compared to placebo in participants with gulf war illness (GWI)
Time frame: Baseline to 8 weeks
Change in glutathione levels
Measure the change of brain glutathione levels with magnetic resonance spectroscopy (MRS) in a subset of both arms of study at baseline and 8 weeks.
Time frame: Baseline to 8 Weeks
Change in number of participants with treatment-related adverse events
Change in number of participants with treatment-related adverse events from baseline to 16 weeks during the intervention period as assessed by a safety questionnaire.
Time frame: Baseline to 16 Weeks
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Boston, Massachusetts, United States
VA New Jersey Health Care System War Related Illness and Injury Study Center
East Orange, New Jersey, United States
RECRUITINGWeill Cornell Medical College
New York, New York, United States
ACTIVE_NOT_RECRUITINGRTI International
Durham, North Carolina, United States
ACTIVE_NOT_RECRUITINGMichael E. DeBakey VA Medical Center
Houston, Texas, United States
RECRUITING