Gulf War SyndromeEarly Phase 1NACNCT04987775
GWICTIC: NAC Mechanistic Study in Gulf War Veterans
A Early Phase 1 study testing N-Acetyl Cysteine in people with Gulf War Syndrome, run by Nova Southeastern University at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 47 to 70 years
- Conditions the study is for
- Gulf War Syndrome
- What is being tested?
- N-Acetyl Cysteine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 170 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Nov 2023to Apr 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 47 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Karen Kesler, PhD contact
7 sites in 1 country
United States7 sites, 4 recruiting
- Active, not recruiting
Boston University Medical School
Boston, Massachusetts, 02215
- Active, not recruiting
RTI International
Durham, North Carolina, 27709
- Recruiting
VA New Jersey Health Care System War Related Illness and Injury Study Center
East Orange, New Jersey, 07018
Helena Chandler, PhD, 973-676-3580, Helena.Chandler@va.gov
Helena Chandler, PhD
- Recruiting
Nova Southeastern University
Fort Lauderdale, Florida, 33314
Nancy Klimas, MD, nklimas@nova.edu
Amaanpreet Cheema, PhD, acheema@nova.edu
- Recruiting
Michael E. DeBakey VA Medical Center
Houston, Texas, 77030
Drew Helmer, MD, 713-440-4452, Drew.Helmer@va.gov
Drew Helmer, MD
- Active, not recruiting
Weill Cornell Medical College
New York, New York, 10021
- Recruiting
VA Palo Alto Health Care System War Related Illness and Injury Study Center
Palo Alto, California, 94304
Wes Ashford, MD, 650-852-3316, wes.ashford@va.gov
Wes Ashford, MD
About this study
Official title: Mechanisms of Oxidative Stress During N-Acetyl Cysteine (NAC) Supplementation in Veterans With Gulf War Illness (GWI)
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.
Read the detailed description
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.
- Conditions
- Gulf War Syndrome
- Being tested
- N-Acetyl Cysteine, Placebo
- Keywords
- CNS Recovery, N-Acetyl Cysteine (NAC), Gulf War Illness, Placebo
- Medical subject headings
- Persian Gulf Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Acetyl CysteineDrug
Also called NAC
900mg 2x daily
PlaceboDrug
Also called NAC Placebo
Matching placebo bid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess glutathione levels
Change in glutathione levels after NAC supplementation compared to placebo in participants with gulf war illness (GWI)
Measured: Baseline to 8 weeks
Secondary outcomes (2)
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.
Measured: 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.
Measured: Baseline to 16 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start30 Nov 2023
- Primary completionApr 2026 (estimated)
- Study completionApr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gulf War SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants enrolled will be randomized into one of two arms: NAC or Placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nova Southeastern University
- Sponsor type
- University, hospital or other
- Collaborators
- RTI International, Boston University, Weill Medical College of Cornell University
- Responsible party
- Sponsor
- Investigators
- Nancy Klimas, MD, Principal investigator, Nova Southeastern Univeristy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04987775
- Sponsor's protocol ID
- GWICTIC-NAC
- Acronym
- NAC
- Status last verified
- Jul 2025
- First submitted
- 7 Jun 2021
- Last updated
- 8 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The plan is to release primary results from the study. Data are the property of Nova Southeastern University, but data and publication thereof will not be unduly withheld.
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Oxidative Stress During N-Acetyl Cysteine (NAC) Supplementation in Veterans With Gulf War Illness (GWI)
- ClinicalTrials.gov ID
- NCT04987775
- Acronym / sponsor ID
- NAC / GWICTIC-NAC
- Conditions
- Gulf War Syndrome
- Keywords
- CNS Recovery, N-Acetyl Cysteine (NAC), Gulf War Illness, Placebo
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Nova Southeastern UniversityUniversity, hospital or other
- Collaborators
- RTI International, Boston University, Weill Medical College of Cornell University
- Study start
- 30 Nov 2023 (actual)
- Primary completion
- Apr 2026 (estimated)
- Study completion
- Apr 2026 (estimated)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants enrolled will be randomized into one of two arms: NAC or Placebo.
| Arm | Type | Receives |
|---|---|---|
| N-Acetyl Cysteine (NAC) | Active comparator | Drug: N-Acetyl CysteineParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 47 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- Able to provide written consent to the study
- Agrees to participate in follow-up visits.
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-Acetyl CysteineAlso: NAC900mg 2x daily | Drug | N-Acetyl Cysteine (NAC) |
| PlaceboAlso: NAC PlaceboMatching placebo bid | Drug | Placebo |
Primary outcome
Assess glutathione levels
Time frame: Baseline to 8 weeks
Change in glutathione levels after NAC supplementation compared to placebo in participants with gulf war illness (GWI)
2 secondary outcomes
Change in glutathione levels
Time frame: Baseline to 8 Weeks
Change in number of participants with treatment-related adverse events
Time frame: Baseline to 16 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2025.
- Individual participant dataSharing planned: No. The plan is to release primary results from the study. Data are the property of Nova Southeastern University, but data and publication thereof will not be unduly withheld.
Related trials for Gulf War Syndrome
Not yet recruiting
Pycnogenol (French Maritime Pine Bark) for the Treatment of Gulf War Illness
Gulf War Syndrome
RecruitingPhase 1
Clinical Evaluation of Montelukast in Veterans With Gulf War Illness
Gulf War Syndrome
Recruiting
Mechanisms of Gulf War Illness
Gulf War Illness, Irritable Bowel Syndrome
RecruitingPhase 2
Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)
Gulf War Syndrome, Adult Growth Hormone Deficiency
RecruitingPhase 2
Resistant Potato Starch to Alleviate GWI
Gulf War Illness
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karen Kesler, PhD contact
Nancy Klimas, MD principal investigator
Nova Southeastern Univeristy
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing N-Acetyl Cysteine in people with Gulf War Syndrome, run by Nova Southeastern University at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nancy Klimas, MD (9542622855, nklimas@nova.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess glutathione levels (time frame: Baseline to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2025.