N-Acetyl Cysteine for Gulf War Syndrome

(NAC Trial)

Recruiting at 6 trial locations

Overseen By Karen Kesler, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nova Southeastern University

Must not be taking: Antivirals, Blood thinners, Herbal medicine

Disqualifiers: Severe TBI, Schizophrenia, Alcoholism, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether N-Acetyl Cysteine (NAC) can manage Gulf War Syndrome by reducing oxidative stress and boosting antioxidants in the body. Researchers will compare NAC to a placebo to determine its effect on specific blood and brain chemicals linked to this condition. The trial is suitable for those who served in the Gulf War between August 1990 and July 1991 and meet specific health criteria related to Gulf War Illness. Participants will take either NAC or a placebo for eight weeks. As an Early Phase 1 trial, this research aims to understand how NAC works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain antiviral medications or herbal medicines within 30 days before joining. If you're on blood-thinning medications or have uncontrolled diabetes, you might not be eligible.

Is there any evidence suggesting that N-Acetyl Cysteine is likely to be safe for humans?

Research has shown that N-Acetyl Cysteine (NAC) is generally safe for people. The FDA has approved it to treat acetaminophen overdose, indicating it is usually well-tolerated at certain doses. In studies where NAC was used for other conditions, most patients tolerated it well. Some experienced mild side effects, such as nausea, rash, or a slight upset stomach. These side effects were uncommon and typically easy to manage. Overall, evidence indicates that NAC is safe, but like any treatment, monitoring for unexpected reactions is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Gulf War Syndrome?

N-Acetyl Cysteine (NAC) is unique because it targets oxidative stress, which is thought to play a role in Gulf War Syndrome. Unlike other treatments that mainly focus on managing symptoms, NAC works by replenishing glutathione, a powerful antioxidant, potentially addressing the root cause. Researchers are excited about NAC because it offers a new approach with the possibility of improving overall cellular health, which could lead to more comprehensive relief for those affected by the syndrome.

What evidence suggests that N-Acetyl Cysteine might be an effective treatment for Gulf War Syndrome?

This trial will compare N-Acetyl Cysteine (NAC) with a placebo to evaluate its effectiveness for Gulf War Syndrome. Research suggests that NAC might help by reducing oxidative stress, which occurs when harmful molecules overwhelm the body. NAC may help balance these molecules. Studies have shown that NAC can increase levels of glutathione (GSH), an antioxidant that combats these harmful molecules. This is important because people with Gulf War Syndrome often have low GSH levels. Although the data remains preliminary, NAC shows promise in improving symptoms related to this condition. ^{1 5 6 7 8}

Who Is on the Research Team?

Nancy Klimas, MD

Principal Investigator

Nova Southeastern Univeristy

Are You a Good Fit for This Trial?

This trial is for Gulf War veterans aged 47-70 who served between August 1990 and July 1991, meet the criteria for Gulf War Illness, and can consent to the study. They must not have severe mental health issues or substance abuse problems, no recent participation in other trials, and should not be on dialysis or have certain chronic infections.

Inclusion Criteria

I have conditions like high blood pressure or diabetes, but they are well-managed.

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

I am currently receiving dialysis.

Exclusion Criteria

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)

I do not have chronic infections like HIV, HBV, or HCV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either N-Acetyl-L-Cysteine (NAC) or placebo two times a day for 8 weeks

8 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Follow-up assessments to monitor adverse events and glutathione levels

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetyl Cysteine
• Placebo

Trial Overview

The GWICTIC study is testing whether N-Acetyl Cysteine (NAC) can improve oxidative stress and antioxidant levels in those with Gulf War Syndrome compared to a placebo. It involves blood tests and neuroimaging to measure changes in serum glutathione concentration and brain oxidative stress.

How Is the Trial Designed?

Group I: N-Acetyl Cysteine (NAC) Active Control 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

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.

N-Acetyl Cysteine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Acetylcysteine for:

• Mucolytic therapy
• Acetaminophen overdose

Approved in United States as Acetylcysteine for:

• Mucolytic therapy
• Acetaminophen overdose

Approved in Canada as Acetylcysteine for:

• Mucolytic therapy
• Acetaminophen overdose

Approved in Japan as Acetylcysteine for:

• Mucolytic therapy
• Acetaminophen overdose

Who Is Running the Clinical Trial?

Nova Southeastern University

Lead Sponsor

Trials

103

Recruited

12,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

RTI International

Collaborator

Trials

201

Recruited

942,000+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

Miami VA Healthcare System

Collaborator

Trials

18

Recruited

2,400+

Published Research Related to This Trial

N-Acetylcysteine is effective as a mucolytic agent for chronic bronchitis and as an antidote for paracetamol poisoning, with peak plasma concentrations achieved within 1 to 2 hours after oral doses of 200 to 400 mg.

While it has significant therapeutic benefits, common side effects include nausea, vomiting, and diarrhea, and it may interact with other drugs, particularly paracetamol and certain anticancer agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. Holdiness, MR.[2022]

N-acetylcysteine (NAC) is not only a mucolytic but also has multiple therapeutic roles, including managing acetaminophen poisoning and acting as an antioxidant to protect lungs from damage due to smoking and pollution.

Its ability to break disulfide bridges and scavenge free radicals suggests potential benefits in treating connective tissue diseases and enhancing overall health in life extension diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetylcysteine: a drug with an interesting past and a fascinating future. Ziment, I.[2018]

N-acetylcysteine (NAC) is effective in promoting the synthesis of glutathione (GSH), which helps detoxify the body and combat oxidative stress, making it beneficial for conditions like HIV, cancer, and heart disease.

NAC is the primary treatment for acetaminophen-induced liver damage and also serves as a chelating agent for acute heavy metal poisoning, protecting organs and aiding in metal elimination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of N-acetylcysteine. Kelly, GS.[2013]

In a study involving six healthy volunteers, N-acetylcysteine (NAC) at a daily dose of 600 mg for two weeks did not show any detectable levels in bronchoalveolar lavage fluid, suggesting it does not directly act as a mucolytic by breaking disulfide bonds in the lungs.

While NAC did not alter cysteine or glutathione levels in the lavage fluid, it did lead to a significant increase in plasma glutathione, indicating that its effects may be mediated through different mechanisms rather than direct mucolytic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid. Cotgreave, IA., Eklund, A., Larsson, K., et al.[2013]

Oral administration of N-acetylcysteine (NAC) for 5 days increased cysteine levels in human plasma and rat bronchoalveolar lavage, but did not significantly change glutathione levels or the stimulated release of reactive oxygen species from phagocytic cells.

NAC did lead to a small but significant increase in spontaneous generation of superoxide anion from rat alveolar macrophages and hydrogen peroxide from human neutrophils, suggesting a potential role in modulating oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. Drost, E., Lannan, S., Bridgeman, MM., et al.[2013]

N-acetylcysteine (NAC) is a versatile compound that serves as a precursor to important antioxidants and has been used historically for treating respiratory issues and acetaminophen overdose.

Recent studies suggest that NAC may have therapeutic potential in a variety of conditions, including cancer, heart disease, and HIV, due to its strong antioxidant properties that combat free radical damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine. [2013]

N-acetylcysteine (NAC) has shown promising results as a treatment for the toxicity caused by the chemical warfare agent sulphur mustard, particularly in cases of inhalation, due to its ability to replenish the antioxidant glutathione in the body.

While NAC has a strong safety profile and protective properties against various toxicants, further controlled clinical trials are necessary to establish its optimal dosage and efficacy specifically for treating inhaled sulphur mustard exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetylcysteine as a treatment for sulphur mustard poisoning. Sawyer, TW.[2023]

N-acetylcysteine is primarily known as the antidote for acetaminophen overdose, but it also has several other scientifically supported uses, including preventing exacerbations in chronic obstructive pulmonary disease and protecting against kidney damage during imaging procedures.

Emerging evidence suggests that N-acetylcysteine may help in treating conditions like pulmonary fibrosis, infertility in certain patients, and potentially even in cancer prevention and protecting against hearing loss in patients undergoing dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine: multiple clinical applications. Millea, PJ.[2022]

N-Acetyl-l-cysteine (NAC) serves as a precursor to glutathione, helping to detoxify reactive oxygen species, which is particularly beneficial in managing oxidative stress in chronic obstructive pulmonary disease (COPD).

The study found that low doses of NAC administered chronically provide sustained antioxidant and anti-inflammatory effects, while high doses given acutely produce a stronger immediate response, highlighting the importance of dosage in NAC's therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of dose and exposition time in the effectiveness of N-Acetyl-l-cysteine treatment in A549 human epithelial cells. Montero, P., Roger, I., Estornut, C., et al.[2023]

In a study involving 70 cystic fibrosis (CF) patients over 24 weeks, those taking oral N-acetylcysteine (NAC) maintained or slightly improved their lung function, while those on placebo experienced a decline, indicating NAC's potential to stabilize lung health in CF.

Despite the positive effects on lung function, NAC did not significantly reduce levels of human neutrophil elastase (HNE), a marker of inflammation, suggesting that while NAC may help with lung function, its mechanism of action regarding inflammation needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. Conrad, C., Lymp, J., Thompson, V., et al.[2015]

In a randomized clinical trial involving mechanically ventilated patients with acute respiratory distress syndrome, N-acetylcysteine (NAC) showed a positive effect on improving consciousness and respiratory function after 3 to 4 days of treatment.

However, NAC did not significantly impact overall vital signs, duration of ICU stay, mechanical ventilation time, or mortality rates compared to the control group, suggesting its benefits may be limited to specific aspects of recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of N-Acetylcysteine on the treatment of acute respiratory distress syndrome in mechanically ventilated patients admitted to the intensive care unit. Ghorbi, M., Rashidi, M., Olapour, A., et al.[2023]

Citations

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GWICTIC: NAC Mechanistic Study in Gulf War Veterans

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 ...

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nova.edu

nova.edu/inim/research-studies/gulf-war-illness.html

Gulf War Illness Research

... Gulf War Illness: N-Acetyl Cysteine. This open-label dose-comparison study utilizes a combination therapy to assess efficacy in homeostasis reset. Principal ...

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Environmental Health with Lindsay Kastner (SPH'25)

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3279571/

The relationship between Gulf war illness, brain N-acetyl ...

A previous study (1) suggested that individuals with Gulf War Illness (GWI) had reduced quantities of the neuronal marker N-acetyl aspartate (NAA) in the basal ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10405325/

Adverse effect propensity: A new feature of Gulf War illness ...

Total AE Propensity (TAEP) was greater in veterans with Gulf War illness (VGWI). Pesticides and radiation predicted greater TAEP, while copper appeared ...

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ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK537183/

N-Acetylcysteine - StatPearls - NCBI Bookshelf - NIH

N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity. NAC has FDA approval for treating potentially hepatotoxic doses of acetaminophen ...

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accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf

Acetadote (acetylcysteine) Injection Package Insert

Safety Study. A randomized, open-label, multi-center clinical study was conducted in Australia to compare the rates of anaphylactoid reactions ...

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go.drugbank.com

go.drugbank.com/drugs/DB06151

Acetylcysteine: Uses, Interactions, Mechanism of Action

Acetylcysteine is a medication that can be used as a mucolytic in patients with certain lung conditions and as an antidote for acetaminophen overdose.