N-acetyl Cysteine for Multiple Sclerosis

(NACPMS Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests if N-acetyl cysteine (NAC) can help people with progressive multiple sclerosis by protecting brain cells and reducing inflammation. Participants will be divided into two groups, with one group taking NAC. N-acetyl cysteine (NAC) has been studied for its potential benefits in various conditions, including multiple sclerosis, cannabis use disorder, and chronic obstructive pulmonary disease.

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.

What data supports the effectiveness of the drug N-acetyl cysteine for treating multiple sclerosis?

Research shows that N-acetyl cysteine (NAC) has antioxidative and anti-inflammatory effects, which have been beneficial in treating chronic respiratory diseases like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). These properties might suggest potential benefits for other inflammatory conditions, such as multiple sclerosis. ^{1 2 3 4 5}

Is N-acetylcysteine generally safe for human use?

N-acetylcysteine (NAC) is generally considered safe for human use, with common side effects being mild and including nausea, vomiting, and diarrhea. It is widely used in respiratory medicine and as an antidote for acetaminophen poisoning, with studies showing a similar safety profile at both standard and higher doses. ^{1 3 6 7 8}

How is the drug N-acetyl cysteine unique for treating multiple sclerosis?

N-acetyl cysteine (NAC) is unique for treating multiple sclerosis because it acts as an antioxidant, reducing oxidative stress that contributes to nerve damage in the disease. Unlike other treatments that mainly focus on modulating the immune system, NAC directly scavenges free radicals and helps restore glutathione levels, potentially offering neuroprotective benefits. ^{1 9 10 11 12}

Research Team

Eligibility Criteria

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.

I've been on a stable treatment for my condition for over 3 months.

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.

Trial Timeline

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

Treatment Details

Interventions

• N-acetyl cysteine (Antioxidant)
• Placebo (Other)

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.

Participant Groups

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 Canada for the following indications:

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+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Findings from Research

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-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]

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 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 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in the Use of N-Acetylcysteine in Chronic Respiratory Diseases. [2023]

2. Italy pubmed.ncbi.nlm.nih.gov

N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. [2016]

3. England 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. [2020]

4. 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]

5. England 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. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases: A Review. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of N-acetylcysteine. [2022]

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

N-acetylcysteine in handgrip exercise: plasma thiols and adverse reactions. [2021]

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

Tolerability and Safety of Combined Glatiramer Acetate and N-Acetylcysteine in Relapsing-Remitting Multiple Sclerosis. [2019]

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

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis. [2023]

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

A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine. [2022]

12. United States 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. [2023]