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

Trial Summary

What is the purpose of this trial?

This trial will test if NAC can help veterans with Gulf War Illness by increasing antioxidants in their bodies. The goal is to reduce brain inflammation and improve symptoms like fatigue and pain. N-acetylcysteine (NAC) has been shown to reduce oxidative stress and inflammation in both human and animal models.

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.

What evidence supports the effectiveness of the drug N-Acetyl Cysteine for treating Gulf War Syndrome?

N-Acetyl Cysteine (NAC) has shown positive effects in treating respiratory conditions and reducing oxidative stress, which may be relevant for Gulf War Syndrome. It has been effective in improving lung function in cystic fibrosis and treating respiratory distress syndrome, suggesting potential benefits for similar symptoms in Gulf War Syndrome. ^{1 2 3 4 5}

Is N-Acetyl Cysteine generally safe for humans?

N-Acetyl Cysteine (NAC) is generally considered safe for humans, with common side effects including nausea, vomiting, and diarrhea. It is used for various conditions, such as treating acetaminophen poisoning and reducing mucus in lung diseases, and has antioxidant properties. While some biochemical effects are observed, they are not clinically significant. ^{1 6 7 8 9}

How does the drug N-Acetyl Cysteine differ from other treatments for Gulf War Syndrome?

N-Acetyl Cysteine (NAC) is unique because it acts as a powerful antioxidant by boosting glutathione levels, which helps protect cells from damage caused by oxidative stress. This mechanism is particularly relevant for Gulf War Syndrome, where oxidative stress is a suspected factor, and NAC's ability to detoxify and reduce inflammation makes it a novel option compared to other treatments. ^{2 4 5 10 11}

Research Team

Nancy Klimas, MD

Principal Investigator

Nova Southeastern Univeristy

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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 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 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]

References

1. Netherlands 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. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. Iran 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical applications of N-acetylcysteine. [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. [2022]

7. Denmark pubmed.ncbi.nlm.nih.gov

No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid. [2013]

8. England 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. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine: multiple clinical applications. [2022]