N-acetylcysteine for Gaucher Disease

Recruiting at 1 trial location

Overseen By Reena V. Kartha, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must be taking: ERT, SRT

Must not be taking: Antioxidants

Disqualifiers: Asthma, Pregnancy, MRI issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 9 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a treatment called N-acetylcysteine (NAC) affects blood and brain chemicals related to stress and inflammation in people with Type 1 Gaucher disease. Researchers aim to determine if the disease alters these chemical levels. The trial suits individuals who have maintained stable therapy for Gaucher disease for at least two years and have not recently used certain antioxidants. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that Gaucher disease patients stay on their current enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) at a stable dose. However, you must stop taking antioxidants like coenzyme Q-10, vitamin C, or vitamin E for 3 weeks before and during the study.

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

Studies have shown that N-acetylcysteine (NAC) is very safe. Most people tolerate it well, and serious side effects rarely occur, especially when taken orally, as in this trial. Some research highlights its excellent safety record, noting that unwanted effects are uncommon.

NAC is used in different doses for various conditions, but it remains safe even at higher doses. In this trial, doses will start at 3600 mg per day and may increase to 7200 mg per day. Past research indicates that NAC is not expected to cause significant side effects at these levels.

Overall, the safety of NAC in many studies makes it a reliable choice for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Gaucher disease?

N-acetylcysteine is unique because it targets oxidative stress, which isn't a primary focus of current Gaucher disease treatments. While most standard therapies for Gaucher disease, like enzyme replacement therapy, aim to replace deficient enzymes or reduce glucocerebroside accumulation, N-acetylcysteine works by potentially increasing brain glutathione levels to improve overall cellular health. This novel approach could address neurological symptoms that aren't effectively managed by existing treatments. Researchers are excited about this treatment because it offers a new avenue to enhance the quality of life for patients with Gaucher disease, especially those who experience neurological complications.

What evidence suggests that N-acetylcysteine might be an effective treatment for Gaucher Disease?

Research has shown that N-acetylcysteine (NAC), which participants in this trial will receive, can increase levels of glutathione, an important antioxidant, in both the brain and blood. This is crucial for conditions like Gaucher disease, where free radical damage is a concern. Studies have also demonstrated that NAC can reduce inflammation by addressing issues in the cell's energy centers, a problem in many rare diseases. In individuals with Gaucher and Parkinson's diseases, NAC boosted brain and blood glutathione levels. These findings suggest that NAC could potentially help manage symptoms of Gaucher disease by reducing harmful processes in the body. ^{1 2 6 7 8}

Who Is on the Research Team?

Reena V. Kartha, PhD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This study is for adults over 18 with stable Type 1 Gaucher disease (GD1) who have been on consistent enzyme replacement or substrate reduction therapy for at least two years. Healthy volunteers matched by age can also join. Participants must not be pregnant, lactating, using certain antioxidants, or have conditions like asthma being treated currently.

Inclusion Criteria

I have been on the same enzyme or substrate replacement therapy for at least 2 years.

I changed my treatment 6 months ago and my condition is stable.

I am healthy and my age matches the study's requirements.

Exclusion Criteria

You are allergic to N-acetylcysteine.

I am not pregnant, breastfeeding, and if of child-bearing age, I am using effective birth control.

Unable to adhere to study protocol for whatever reason.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

GD1 patients receive oral N-acetylcysteine (NAC) for approximately 90 days, with multiple study visits for assessments and MRI scans.

9 months

7 visits (in-person) for GD1 patients

Follow-up

Participants are monitored for changes in blood and brain chemical levels, including glutathione and myo-inositol, after treatment.

3 months

3 visits (in-person) for healthy volunteers

Extension

Potential continuation of monitoring for long-term changes in chemical levels in GD1 patients.

3 months

What Are the Treatments Tested in This Trial?

Interventions

• N-acetylcysteine

Trial Overview

The trial is investigating the effect of N-acetylcysteine on oxidative stress and inflammation in individuals with GD1 compared to healthy volunteers. It measures blood and brain chemicals to see if levels are different due to GD1.

How Is the Trial Designed?

Group I: N-acetylcysteine Experimental Treatment 1 Intervention

The first 10 GD1 subjects will take 1800mg NAC twice daily (3600mg/day) orally for approximately 90 days. An interim analysis will be performed to determine if this dose produces changes in systemic redox status and brain glutathione (GSH) levels. If no signal of a significant change is observed, the remaining 20 subjects will receive up to 3600 mg NAC orally twice a day (7200 mg/day).

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

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Center for Advancing Translational Science (NCATS)

Collaborator

Trials

100

Recruited

32,100+

Rare Diseases Clinical Research Network

Collaborator

Trials

69

Recruited

19,200+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Lysosomal Disease Network

Collaborator

Trials

7

Recruited

370+

Published Research Related to This Trial

N-acetylcysteine (NAC) has a wide range of clinical applications, including treatment for paracetamol overdose and various disorders, due to its antioxidative properties and ability to restore impaired cellular components.

NAC's unique effectiveness is likely due to its ability to reduce disulfide bonds in proteins, which alters their structure and function, although more research is needed to fully understand its mechanisms and how it interacts with cell signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. Samuni, Y., Goldstein, S., Dean, OM., et al.[2022]

In a study involving 12 hemodialysis patients, intravenous administration of 2 g of N-acetylcysteine (NAC) over 3 hours was found to be safe, with no observed side effects during the six dialysis sessions.

NAC reached a steady state concentration after the fourth infusion, indicating effective pharmacokinetics in dialysis patients, with a significant dialytic clearance of 5.52 l/h.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. Soldini, D., Zwahlen, H., Gabutti, L., et al.[2018]

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) 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 mortality and pancreatic damage in rats with acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid, suggesting its potential as a treatment option.

NAC improved various health markers, including urine output, blood oxygen levels, and reduced harmful substances in the pancreas and lungs, indicating its protective effects during ANP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats. Mumcu, S., Alhan, E., Türkyilmaz, S., et al.[2013]

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