N-Acetyl Cysteine for Gulf War Syndrome
(NAC Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Nova Southeastern University
Must not be taking: Antivirals, Blood thinners, Herbal medicine
Disqualifiers: Severe TBI, Schizophrenia, Alcoholism, others
Approved in 5 Jurisdictions
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.12345
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.16789
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.2451011
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.
See 11 more
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.
See 10 more
Trial 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 (Antioxidant)
- Placebo (Other)
Trial OverviewThe 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
2Treatment groups
Active Control
Placebo Group
Group I: N-Acetyl Cysteine (NAC)Active Control1 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: PlaceboPlacebo Group1 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, Australia 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
🇦🇺 Approved in Australia as Acetylcysteine for:
- Mucolytic therapy
- Acetaminophen overdose
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nova Southeastern UniversityFort Lauderdale, FL
VA Palo Alto Health Care System War Related Illness and Injury Study CenterPalo Alto, CA
RTI InternationalDurham, NC
Michael E. DeBakey VA Medical CenterHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Nova Southeastern UniversityLead Sponsor
Weill Medical College of Cornell UniversityCollaborator
RTI InternationalCollaborator
Boston UniversityCollaborator
Miami VA Healthcare SystemCollaborator
References
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]To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways.
N-Acetylcysteine as a treatment for sulphur mustard poisoning. [2023]In the long and intensive search for effective treatments to counteract the toxicity of the chemical warfare (CW) agent sulphur mustard (H; bis(2-chloroethyl) sulphide), the most auspicious and consistent results have been obtained with the drug N-acetylcysteine (NAC), particularly with respect to its therapeutic use against the effects of inhaled H. It is a synthetic cysteine derivative that has been used in a wide variety of clinical applications for decades and a wealth of information exists on its safety and protective properties against a broad range of toxicants and disease states. Its primary mechanism of action is as a pro-drug for the synthesis of the antioxidant glutathione (GSH), particularly in those circumstances where oxidative stress has exhausted intracellular GSH stores. It impacts a number of pathways either directly or through its GSH-related antioxidant and anti-inflammatory properties, which make it a prime candidate as a potential treatment for the wide range of deleterious cellular effects that H is acknowledged to cause in exposed individuals. This report reviews the available literature on the protection afforded by NAC against the toxicity of H in a variety of model systems, including its efficacy in treating the long-term chronic lung effects of H that have been demonstrated in Iranian veterans exposed during the Iran-Iraq War (1980-1988). Although there is overwhelming evidence supporting this drug as a potential medical countermeasure against this CW agent, there is a requirement for carefully controlled clinical trials to determine the safety, efficacy and optimal NAC dosage regimens for the treatment of inhaled H.
Effect of N-Acetylcysteine on the treatment of acute respiratory distress syndrome in mechanically ventilated patients admitted to the intensive care unit. [2023]Background: N-acetylcysteine (NAC) is an antioxidant derived from the amino acid cysteine and is one of the drugs used in the treatment of respiratory diseases. The aim of this study was to investigate the effect of NAC on the treatment of acute respiratory distress syndrome in mechanically ventilated patients admitted to the intensive care unit. Methods: This study was a randomized clinical trial. Patients under mechanical ventilation admitted to the intensive care unit were examined. Patients in the intervention group received daily 150 mg/kg of NAC on the first day of admission and then 50 mg/kg up to the fourth day of admission. Patients in the control group received routine care. The vital signs, level of consciousness, and other important variables were recorded. Data were analyzed using statistical tests and SPSS software version 24. Results: There was no significant difference between MAP, heart rate, respiratory rate, O2Sat, APACHE II score, and pulmonary capacity of the patients in the two groups on the first, second, third and fourth days after the intervention (p>0.05 ). There was no significant difference between the level of consciousness (according to GCS criteria), respiratory index (PAO2/FIO2) and PEEP of patients in the two study groups within 1 to 2 days after the intervention (p>0.05). There was a significant difference between the level of consciousness (based on GCS criteria), respiratory index (PAO2/FIO2) and PEEP of patients in the two study groups within 3 to 4 days after the intervention (p<0.05). There was no significant difference between the duration of hospitalization in the ICU, the time required for mechanical ventilation and the mortality rate of the patients in the two groups (p>0.05). Conclusion: It seems that N-acetylcysteine has a positive effect on the treatment of acute respiratory distress syndrome in mechanically ventilated patients admitted to the intensive care unit.
Lack of effect of N-acetylcysteine on the release of oxygen radicals from neutrophils and alveolar macrophages. [2013]N-acetylcysteine (NAC) is rapidly de-acetylated in vivo to cysteine (CYSH), a precursor of glutathione (GSH) which is an antioxidant in cells and body fluids. We investigated the effect of oral administration of N-acetyl cysteine for 5 days on the spontaneous and stimulated generation of hydrogen peroxide (H2O2) and superoxide anion (O2-) from human and rat phagocytic leucocytes. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) in control rats and rats given NAC in their drinking water. Neutrophils (PMNL) were harvested from whole blood in normal nonsmoking volunteers before and after NAC was given by mouth. The stimulated release of H2O2 and O2 from both rat AM and human PMN was not changed by administration of NAC. However, a small but significant increase was observed in both the spontaneous generation of O2- from rat AM and the spontaneous generation of H2O2 from human PMNL. Administration of NAC significantly increased cysteine levels in human plasma and rat BAL, but the levels in human PMNL and rat AM after NAC did not differ from control levels. GSH levels were not altered significantly by NAC.
Clinical applications of N-acetylcysteine. [2013]N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is converted in the body into metabolites capable of stimulating glutathione (GSH) synthesis, promoting detoxification, and acting directly as free radical scavengers. Administration of NAC has historically been as a mucolytic agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased GSH or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is currently the mainstay of treatment for acetaminophen-induced hepatotoxicity. N-acetylcysteine also appears to have some clinical usefulness as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals.
Clinical pharmacokinetics of N-acetylcysteine. [2022]N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of cardiotoxicity by doxorubicin and haemorrhagic cystitis from oxazaphosphorines. After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reported as 0.190 to 0.211 L/h/kg and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced N-acetylcysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate. Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and haematological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.
No penetration of orally administered N-acetylcysteine into bronchoalveolar lavage fluid. [2013]Six healthy volunteers underwent bronchoalveolar lavage (BAL) before and after receiving N-acetylcysteine (NAC) 600 mg daily for 2 weeks. Free and total NAC, cysteine and glutathione were determined in the lavage fluid, lavage cells and plasma. No NAC was demonstrated, free or bound in disulfides, in either of the lavage components; furthermore, the cysteine and glutathione content of these components and their respective redox states were unaltered during therapy. Plasma free and total cysteine content was unaltered by administration of the drug, but both free and total plasma glutathione increased significantly. Free NAC could not be detected in plasma following dosing. However, a mean of 0.3 nmol/100 microliters plasma was released from disulfides in plasma following reduction with dithiothreitol. N-acetylcysteine has been proposed to act as a mucolytic by cleavage of disulfide bonds. Our findings do not support this direct mode of action and alternative mechanisms of action must be sought.
Influence of dose and exposition time in the effectiveness of N-Acetyl-l-cysteine treatment in A549 human epithelial cells. [2023]N-Acetyl-l-cysteine (NAC) acts as a precursor of the tripeptide glutathione (GSH), one of the principal cell mechanisms for reactive oxygen species (ROS) detoxification. Chronic obstructive pulmonary disease (COPD) is associated with enhanced inflammatory response and oxidative stress and NAC has been used to suppress various pathogenic processes in this disease. Studies show that the effects of NAC are dose-dependent, and it appears that the efficient doses in vitro are usually higher than the achieved in vivo plasma concentrations. However, to date, the inconsistencies between the in vitro NAC antioxidant and anti-inflammatory in vitro effects, by reproducing the in vivo NAC plasma concentrations as well as high NAC concentrations. To do so, A549 were transfected with polyinosinic-polycytidylic acid (Poly (I:C)) and treated with NAC at different treatment periods. Oxidative stress, release of proinflammatory mediators and NFkB activation were analyzed. Results suggest that NAC at low doses in chronic administration has sustained antioxidant and anti-inflammatory effects, while acute treatment with high dose NAC exerts a strong antioxidant and anti-inflammatory response.
Acetylcysteine: a drug with an interesting past and a fascinating future. [2018]N-acetylcysteine (NAC) possesses a free sulfhydryl group that can rupture disulfide bridges. Although it is considered to be a mucolytic, its mucokinetic actions include expectorant, bronchorrheic and mucoregulatory contributions. New uses include the management of acetaminophen poisoning and the scavenging of free radicals liberated by cancer chemotherapy drugs. The antioxidant effects may be of prophylactic value in lungs at risk from smoking, pollution and infection. Other uses proposed for NAC include the therapy of connective tissue diseases and its use as a component in life extension diets.
N-acetylcysteine. [2013]N-acetylcysteine (NAC) is the acetylated precursor of both the amino acid L-cysteine and reduced glutathione (GSH). Historically it has been used as a mucolytic agent in chronic respiratory illnesses as well as an antidote for hepatotoxicity due to acetaminophen overdose. More recently, animal and human studies of NAC have shown it to be a powerful antioxidant and a potential therapeutic agent in the treatment of cancer, heart disease, HIV infection, heavy metal toxicity, and other diseases characterized by free radical oxidant damage. NAC has also been shown to be of some value in treating Sjogren's syndrome, smoking cessation, influenza, hepatitis C, and myoclonus epilepsy.
N-acetylcysteine: multiple clinical applications. [2022]N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for N-acetylcysteine supplementation supported by scientific evidence include prevention of chronic obstructive pulmonary disease exacerbation, prevention of contrast-induced kidney damage during imaging procedures, attenuation of illness from the influenza virus when started before infection, treatment of pulmonary fibrosis, and treatment of infertility in patients with clomiphene-resistant polycystic ovary syndrome. Preliminary studies suggest that N-acetylcysteine may also have a role as a cancer chemopreventive, an adjunct in the eradication of Helicobacter pylori, and prophylaxis of gentamicin-induced hearing loss in patients on renal dialysis.