N-acetylcysteine for Gaucher Disease

Recruiting at1 trial location

Overseen by Reena V. Kartha, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Minnesota

Must be taking: ERT, SRT

Must not be taking: Antioxidants

Disqualifiers: Asthma, Pregnancy, MRI issues, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if a pill called NAC can help people with Type 1 Gaucher disease by reducing harmful processes in their bodies. The study includes both patients with the disease and healthy volunteers to compare results. Researchers hope this will lead to better treatments for the disease.

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.

How does the drug N-acetylcysteine differ from other treatments for Gaucher Disease?

N-acetylcysteine (NAC) is unique because it acts as an antioxidant, which may help reduce inflammation and oxidative stress, unlike standard treatments for Gaucher Disease that typically focus on enzyme replacement. NAC's potential benefits in other conditions, like lung diseases and pancreatitis, suggest it might offer novel therapeutic effects for Gaucher Disease. ^{1 2 3 4 5}

Research Team

Reena V. Kartha, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

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.

Unable to adhere to study protocol for whatever reason.

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

Trial Timeline

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

Treatment Details

Interventions

• N-acetylcysteine (Mucolytic Agent)

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.

Participant Groups

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).

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Shashank Priya

University of Minnesota

Chief Executive Officer since 2023

PhD in Materials Engineering from Penn State

Charles Semba

University of Minnesota

Chief Medical Officer since 2021

MD from the University of Minnesota Medical School

National Center for Advancing Translational Science (NCATS)

Collaborator

Trials

100

Recruited

32,100+

Joni L. Rutter

National Center for Advancing Translational Science (NCATS)

Chief Executive Officer since 2022

PhD in Pharmacology

Dominique C. Pichard

National Center for Advancing Translational Science (NCATS)

Chief Medical Officer since 2023

MD

Rare Diseases Clinical Research Network

Collaborator

Trials

69

Recruited

19,200+

Dr. Steve Cutler

Rare Diseases Clinical Research Network

Chief Executive Officer since 2017

PhD in Molecular Biology, University of Sydney

Dr. Ute Berger

Rare Diseases Clinical Research Network

Chief Medical Officer since 2023

MD from University of Heidelberg

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Dominique C. Pichard

National Center for Advancing Translational Sciences (NCATS)

Chief Medical Officer since 2023

MD

Joni L. Rutter

National Center for Advancing Translational Sciences (NCATS)

Chief Executive Officer since 2022

PhD in Pharmacology

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Jordan Gladman

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Medical Officer

MD from Harvard Medical School

Walter J. Koroshetz

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Executive Officer since 2007

MD from the University of Chicago

Lysosomal Disease Network

Collaborator

Trials

7

Recruited

370+

Findings from Research

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]

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]

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) 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients. [2018]

3. 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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The chemistry and biological activities of N-acetylcysteine. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats. [2013]