N-Acetylcysteine for Chronic Fatigue Syndrome

(NAC ME/CFS Trial)

Overseen By Dikoma C. Shungu, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Mood disorders, Anxiety, Neurological illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential treatment for chronic fatigue syndrome (CFS), a condition characterized by extreme tiredness with no known cure. Researchers are testing N-Acetylcysteine (NAC), a supplement, to determine if it can protect the brain from stress by restoring important chemicals. Participants will receive varying doses of NAC or a placebo to compare results. The trial seeks individuals diagnosed with CFS who can provide informed consent and meet certain baseline levels. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that N-Acetylcysteine (NAC) is generally safe for most adults when taken as a pill. The FDA has approved NAC for other uses, indicating it has undergone safety testing in people.

Some individuals might experience mild side effects like nausea or diarrhea. Serious side effects are rare and mostly occur with very high doses or when administered in other forms, such as through an IV. In this trial, NAC is given as a pill, a common and safe method.

For any concerns, discuss possible side effects with the research team. They are available to help and ensure safety during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic fatigue syndrome?

Unlike the standard treatments for Chronic Fatigue Syndrome, which often focus on managing symptoms with medications like antidepressants, sleep aids, or pain relievers, N-Acetylcysteine (NAC) is unique because it targets oxidative stress and inflammation. Researchers are excited about NAC because it's an antioxidant that can potentially address the underlying biological processes contributing to fatigue. With its different mechanism of action, NAC offers a promising new approach that could lead to more effective relief for those with this challenging condition.

What evidence suggests that N-Acetylcysteine might be an effective treatment for chronic fatigue syndrome?

Research suggests that N-Acetylcysteine (NAC) might aid individuals with chronic fatigue syndrome (CFS) by reducing brain stress. NAC increases levels of glutathione (GSH), a potent antioxidant that protects cells. Previous studies have shown that NAC is safe and effective for issues like paracetamol overdose and thinning mucus. Although direct evidence for NAC's effects on CFS is limited, its ability to boost GSH suggests potential benefits. This trial will evaluate different dosages of NAC, including 900mg/day and 3600mg/day, as potential new treatments for CFS, a condition currently lacking effective treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Dikoma C. Shungu, Ph.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults aged 21-60 with a primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and low baseline GSH levels. Participants must be able to consent. Excluded are those with significant mental disorders, neurological illnesses, unstable medical conditions, history of alcohol abuse, positive drug or pregnancy tests, or contraindications for MRI.

Inclusion Criteria

I am willing and able to give my consent for treatment.

I am between 21 and 60 years old.

I am between 21 and 60 years old.

Exclusion Criteria

You have a history of alcohol abuse.

You have drugs or other substances in your urine when you are tested.

I have significant mental health issues, including mood or anxiety disorders.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive different doses of NAC (0 mg/day, 900 mg/day, 3600 mg/day) or placebo for 4 weeks

4 weeks

1 baseline visit (in-person), self-administration

Follow-up

Participants are monitored for changes in GSH levels and oxidative stress markers after treatment

4 weeks

1 follow-up visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetylcysteine

Trial Overview The trial is testing the effects of N-Acetylcysteine (NAC) at different doses (900mg/day and 3600mg/day) versus a placebo on brain GSH and plasma markers in ME/CFS patients. The goal is to see if NAC can protect against oxidative stress by restoring cortical GSH reserves.

How Is the Trial Designed?

Group I: NAC 3600mg/day Active Control 1 Intervention

Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 3600mg/day caplets for a four week period

Group II: NAC 900mg/day Active Control 1 Intervention

Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 900mg/day caplets for a four week period

Group III: NAC 0mg/day (Placebo) Placebo Group 1 Intervention

Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 0mg/day (placebo) caplets for a four week period

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

Approved in United States as Mucomyst for:

• Mucolytic agent
• Acetaminophen overdose

Approved in European Union as Fluimucil for:

• Mucolytic agent
• Respiratory tract disorders

Approved in Canada as N-Acetylcysteine for:

• Mucolytic agent
• Acetaminophen overdose

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

A study involving 46 healthy participants demonstrated that a new 2% oral N-acetylcysteine formulation is bioequivalent to an existing reference product, meaning they have similar pharmacokinetic profiles.

The new formulation was found to be safe and well tolerated, with most side effects being mild or moderate and not linked to the study drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, open-label, crossover study evaluating bioequivalence of two N-acetylcysteine 2% oral solution formulations in healthy subjects . Donath, F., Armogida, M., Shneyer, L.[2019]

N-acetylcysteine (NAC) significantly reduced the rate of healthcare resource utilization (HCU) events related to COPD exacerbations by 20% compared to placebo, with an even greater reduction of 23% in current and ex-smokers.

In patients using long-acting bronchodilators without inhaled corticosteroids (ICS), NAC led to a remarkable 60% reduction in exacerbation rates compared to those receiving placebo, suggesting NAC could be a beneficial alternative to ICS in certain COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. Papi, A., Zheng, J., Criner, GJ., et al.[2020]

In a study involving 262 participants, long-term treatment with N-acetylcysteine (NAC) significantly reduced the frequency, severity, and duration of influenza-like episodes, particularly in elderly individuals.

While NAC did not prevent influenza virus infection, it notably decreased the number of symptomatic cases, with only 25% of NAC-treated individuals developing symptoms compared to 79% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. De Flora, S., Grassi, C., Carati, L.[2019]

N-acetyl cysteine (NAC) was found to be well-tolerated in individuals with progressive multiple sclerosis (MS), with a high adherence rate of 94%, and a similar incidence of adverse events compared to placebo (60% vs. 80%).

While NAC did not significantly reduce fatigue compared to placebo (mean improvement of 11 points on NAC vs. 18 points on placebo), it did not show a meaningful impact on oxidative biomarkers, suggesting that the dosing or administration method may need to be reconsidered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine. Krysko, KM., Bischof, A., Nourbakhsh, B., et al.[2022]

A clinical trial called NINCFB is investigating the long-term effects of N-acetylcysteine (NAC) on quality of life and exacerbation rates in 119 patients with non-cystic fibrosis bronchiectasis over 52 weeks.

The study aims to provide evidence on NAC's impact on airway bacterial colonization, chronic inflammation, and oxidative stress, which could inform future treatment guidelines for NCFB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial. Liao, Y., Wu, Y., Zi, K., et al.[2022]

In a 12-month study involving 161 bronchiectasis patients, those treated with N-acetylcysteine experienced significantly fewer exacerbations (1.31 vs. 1.98 per patient-year) compared to the control group, indicating its efficacy in reducing flare-ups.

The N-acetylcysteine group also showed a notable improvement in quality of life and a significant reduction in sputum volume, with no severe adverse events reported, suggesting it is a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Qi, Q., Ailiyaer, Y., Liu, R., et al.[2020]

A systematic review of 3 randomized controlled trials and 5 observational studies involving a total of 21,141 patients evaluated the effects of N-acetylcysteine (NAC) on COVID-19 pneumonia, but the evidence for its efficacy was very low due to serious imprecision and indirectness.

While NAC showed no significant impact on in-hospital mortality or the need for ICU admission in RCTs, some observational studies suggested potential benefits, indicating that further research is needed to confirm its safety and effectiveness in treating COVID-19 pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis. Paraskevas, T., Kantanis, A., Karalis, I., 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]

N-acetylcysteine (NAC) has shown potential benefits in various conditions linked to oxidative stress, but clinical trials have produced inconsistent results, particularly in diseases like HIV and chronic obstructive pulmonary disease (COPD).

While NAC is routinely used for treating paracetamol overdose, its efficacy in other areas, such as cancer recurrence and preventing kidney damage from radiocontrast, remains uncertain, with recent studies yielding mixed outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine -- passe-partout or much ado about nothing? Aitio, ML.[2018]

In a 3-month study involving patients with chronic bronchitis, oral N-acetylcysteine (Fabrol) significantly improved symptoms like difficulty in expectoration and cough severity compared to a placebo.

The treatment was well tolerated, with fewer side effects reported in the N-acetylcysteine group than in the placebo group, suggesting it is a safe option for managing chronic bronchitis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. Jackson, IM., Barnes, J., Cooksey, P.[2017]

Oral N-acetylcysteine (NAC) significantly reduces the risk of exacerbations in chronic bronchitis patients, with a relative benefit of 1.56 and a number-needed-to-treat of 5.8 based on a systematic review of 11 trials involving 2,011 patients.

NAC also improves symptoms in 61.4% of patients compared to 34.6% in the placebo group, with a relative benefit of 1.78 and a number-needed-to-treat of 3.7, while showing no increase in gastrointestinal adverse effects compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Stey, C., Steurer, J., Bachmann, S., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04542161

NCT04542161 | Assessment of N-Acetylcysteine as ... This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1043661819308011

Myalgic encephalomyelitis/chronic fatigue syndrome Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04542161?term=AREA%5BConditionSearch%5D(Encephalomyelitis)%20AND%20AREA%5BOverallStatus%5D(RECRUITING)&rank=1

Study Details | Assessment of N-Acetylcysteine as Therapy ... Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8211525/

N-Acetylcysteine: A Review of Clinical Usefulness (an Old ... N-acetylcysteine may be useful as an adjuvant in treating various medical conditions, especially chronic diseases.

6. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac/

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More When taken by mouth: N-acetyl cysteine is likely safe for most adults. N-acetyl cysteine is an FDA-approved prescription drug. It can cause side effects such as ...