N-acetyl Cysteine for Multiple Sclerosis

(NACPMS Trial)

Overseen By Uk Sok Shin, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emmanuelle Waubant

Must be taking: Disease-modifying treatments, Dalfampridine

Must not be taking: Oral glucocorticosteroids, Antioxidants

Disqualifiers: MS relapses, Pregnancy, Bleeding disorders, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 15 months

98 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 help treat progressive multiple sclerosis, a condition where the immune system attacks the protective covering of nerves, worsening symptoms over time. Participants will receive either NAC or a placebo (a pill with no active ingredients) to determine if NAC can slow symptom progression. The trial seeks individuals who have had progressive multiple sclerosis for at least two years and have noticed worsening symptoms, such as needing more support to walk or experiencing cognitive changes. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but you can stay on a stable disease-modifying treatment if it was started more than 3 months before screening. You cannot use medications or supplements with antioxidant properties, including over-the-counter NAC.

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

Previous studies have shown that N-acetyl cysteine (NAC) is well tolerated by people with progressive multiple sclerosis. Research indicates that NAC does not cause significant side effects. One study found that NAC was well tolerated and even suggested improvements in fatigue and antioxidant markers, which help protect cells from damage.

Additionally, the FDA has already approved NAC as a prescription drug for other uses, meaning its safety has been reviewed for those conditions. Overall, NAC appears to have a good safety profile, making it a promising option for further research in treating multiple sclerosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Unlike the standard treatments for multiple sclerosis, such as interferons and monoclonal antibodies, N-acetyl cysteine (NAC) offers a unique approach by acting as a powerful antioxidant. This treatment aims to reduce oxidative stress, which is believed to play a role in the progression of multiple sclerosis. Researchers are excited about NAC because it could complement existing therapies by protecting nerve cells from damage, potentially slowing disease progression and improving patients' quality of life. Additionally, NAC is administered orally, which could make it more convenient for patients compared to some current options that require injections or infusions.

What evidence suggests that N-acetyl cysteine might be an effective treatment for multiple sclerosis?

Research has shown that N-acetyl cysteine (NAC), which participants in this trial may receive, might improve brain function in people with multiple sclerosis (MS). One study found that NAC positively affected how the brain uses glucose, linking it to better patient outcomes. Another study demonstrated that NAC reduced damage from harmful molecules and improved anxiety symptoms in MS patients. Additionally, evidence suggests that NAC may help reduce fatigue and protect cells from damage in progressive MS. These findings indicate that NAC could effectively treat symptoms of progressive MS. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-70 with primary or secondary progressive multiple sclerosis, as per the McDonald criteria. Participants must have experienced progression in the last 2 years and not had MS relapses in the past 6 months. They should not be pregnant, planning surgery, moving soon, or have certain medical conditions like liver issues or bleeding disorders.

Inclusion Criteria

My disability level is moderate to severe but I can still walk.

My symptoms have been getting worse for at least 2 years.

My mobility or cognitive function has worsened in the last 2 years not due to relapses.

Exclusion Criteria

I currently have active stomach or intestinal ulcers.

I have a history of bleeding disorders.

I am currently being treated for cancer or was treated for spreading cancer in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-acetyl cysteine (NAC) or placebo for progressive multiple sclerosis

15 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-acetyl cysteine
• Placebo

Trial Overview The study is testing N-acetyl cysteine (NAC) to see if it can protect nerve cells in patients with progressive multiple sclerosis. Half of the participants will receive NAC while the other half will get a placebo to compare effects.

How Is the Trial Designed?

Group I: N-acetyl cysteine Active Control 1 Intervention

N-acetyl cysteine (NAC) 1200mg t.i.d.

Group II: Placebo Placebo Group 1 Intervention

Placebo 1200mg t.i.d.

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

Approved in United States as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Approved in European Union as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Approved in Canada as Acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Cystic fibrosis

Who Is Running the Clinical Trial?

Emmanuelle Waubant

Lead Sponsor

Trials

1

Recruited

100+

Emmanuelle Waubant, MD PhD

Lead Sponsor

Trials

1

Recruited

100+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a clinical trial involving 42 patients with multiple sclerosis, 8 weeks of oral N-acetylcysteine (NAC) supplementation significantly reduced oxidative stress, as indicated by lower serum malondialdehyde (MDA) levels.

NAC also led to a notable improvement in anxiety symptoms, with a significant decrease in Hospital Anxiety and Depression Scale (HADS-A) scores, suggesting it could be an effective adjunctive therapy for managing anxiety in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis. Khalatbari Mohseni, G., Hosseini, SA., Majdinasab, N., et al.[2023]

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]

A study involving 7 patients with relapsing-remitting multiple sclerosis found that the combination of glatiramer acetate (GA) and N-acetylcysteine (NAC) was safe and well tolerated over a 36-week treatment period.

Given the favorable safety profile observed, further studies to evaluate the efficacy of this combination treatment in MS patients are warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of Combined Glatiramer Acetate and N-Acetylcysteine in Relapsing-Remitting Multiple Sclerosis. Schipper, HM., Arnold, D., GrandʼMaison, F., et al.[2019]

A review of 41 studies found that N-Acetylcysteine (NAC) can be safely used at doses higher than the standard 600 mg/day, with some studies administering up to 3000 mg/day for chronic respiratory diseases.

The safety profile of NAC at higher doses was comparable to standard doses, with gastrointestinal symptoms occurring at similar rates as in control groups, suggesting that increasing the dose may not significantly raise the risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases: A Review. Calverley, P., Rogliani, P., Papi, A.[2023]

N-acetylcysteine (NAC) effectively increases plasma cysteine and glutathione levels, particularly at a dose of 70 mg/kg, which also correlates with improved handgrip exercise performance.

Higher doses of NAC (140 mg/kg) can lead to significant gastrointestinal adverse reactions, suggesting that lower doses may be safer and still effective for enhancing thiol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. Ferreira, LF., Campbell, KS., Reid, MB.[2021]

N-acetylcysteine (NAC) can significantly reduce the production of inflammatory markers like TNF-alpha and TGF-beta1 in alveolar macrophages from patients with idiopathic pulmonary fibrosis (IPF), suggesting its potential as an anti-inflammatory treatment.

In a study involving 16 IPF patients, NAC demonstrated a dose-dependent effect, with the highest concentration (10 mM) leading to substantial suppression of both spontaneous and LPS-stimulated inflammatory responses, indicating its possible role in slowing disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. Cu, A., Ye, Q., Sarria, R., et al.[2016]

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]

The NACPMS trial is a phase 2 study involving 98 patients with progressive multiple sclerosis, aiming to evaluate the safety and efficacy of high-dose N-acetyl cysteine (NAC) in reducing oxidative stress and its impact on brain atrophy over a 15-month period.

Preliminary results from a pilot trial indicated that high-dose NAC was well-tolerated, suggesting it could be a promising add-on therapy to standard care for patients with progressive multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-Acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis (NACPMS) trial: Study protocol for a randomized, double-blind, placebo-controlled add-on phase 2 trial. Schoeps, VA., Graves, JS., Stern, WA., et al.[2023]

N-acetylcysteine (NAC) is effective as a mucolytic agent in cystic fibrosis and serves as a safe antidote for acetaminophen overdose, demonstrating its versatility in treating respiratory conditions.

Due to its antioxidative and anti-inflammatory properties, NAC may benefit patients with chronic respiratory diseases like COPD and asthma, with low toxicity and rare side effects, making it a cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases. Mokra, D., Mokry, J., Barosova, R., et al.[2023]

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 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 double-blind, placebo-controlled trial involving 41 cystic fibrosis (CF) patients and 13 primary ciliary dyskinesia (PCD) patients, N-acetylcysteine (NAC) showed improved lung function in CF patients during periods of lower airway infections.

No beneficial effects of NAC were observed in PCD patients, indicating that the treatment may be more effective for those with cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical effect and the effect on the ciliary motility of oral N-acetylcysteine in patients with cystic fibrosis and primary ciliary dyskinesia. Stafanger, G., Garne, S., Howitz, P., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7033492/

N-acetyl Cysteine Administration Is Associated With Increased ... The results of this study suggest that NAC positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1551714422002671

Study protocol for a randomized, double-blind, placebo ... We aim now to assess the safety, tolerability, and effect of NAC on progression of several MRI, clinical and biological markers in PMS patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10496087/

Effects of N‐acetylcysteine on oxidative stress biomarkers ... N‐acetylcysteine (NAC) supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in multiple sclerosis (MS) patients.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05122559?term=AREA%5BConditionSearch%5D(Multiple%20Sclerosis)%20AND%20AREA%5BBasicSearch%5D(Primary%20progressive)%20AND%20SEARCH%5BLocation%5D(AREA%5BLocationCountry%5DUnited%20States)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING%20OR%20ENROLLING_BY_INVITATION)&rank=3

Neuroprotection With N-acetyl Cysteine for Patients ... This study evaluates the effectiveness of N-acetyl cysteine (NAC) in the treatment of progressive multiple sclerosis. Half of the patients will receive NAC ...

5. neurology.org neurology.org/doi/10.1212/WNL.92.15_supplement.P5.2-093

N-acetyl cysteine for fatigue in progressive multiple sclerosis NAC was well tolerated in progressive MS, with suggestion for sustained fatigue improvement and a positive antioxidant biomarker effect.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36182028/

N-Acetyl Cysteine as a Neuroprotective Agent in ... Our group has recently evaluated the safety of high dose NAC in a pilot trial in PMS with no tolerability concerns. We aim now to assess the ...

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

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

8. 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.