Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1)

NCT02583672 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 160003U54NS065768
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to measure levels of blood and brain chemicals related to oxidative stress and inflammation in healthy volunteers and individuals with Type 1 Gaucher disease (GD1) to see if these levels are altered by GD1.

Conditions

Gaucher Disease Type 1

Keywords

Gaucher Disease; GD1; N-acetylcysteine; glutathione; GSH

Outcome Measures

Primary Outcomes (1)

• Change in subjects with Gaucher disease type 1, in concentration of glutathione in brain (μmol/g)

  The investigators will measure the concentration of glutathione (GSH) in the brains of subjects with Gaucher disease type 1 at 90 days after enrollment, which is the baseline measure. It will again be measured at 180 days after enrollment. These measures will be obtained using NMR spectroscopy (often referred to by the acronym "MRS"). The MRS study will take place over approximately 1.0 hour and will generate measurements of GSH levels from 2-3 brain regions. Scanning may be done in multiple sessions if needed, but will not exceed 1.5 total scanning hours.

  At 90 days and at 180 days

Secondary Outcomes (8)

• In healthy volunteers, determination of level of glutathione in brain (μmol/g)

  90 Days After Enrollment

• Change in subjects with Gaucher disease type 1, in concentration of glutathione in blood (μmol/g)

  Baseline, 45 days, 90 days, 120 days, 150 days, 180 days, and 270 days

• Change in healthy volunteers, in concentration of glutathione in blood (μmol/g)

  Baseline, 45 days, and 90 days

• Change in subjects with Gaucher disease type 1, in concentration of myo-inositol in brain (μmol/g)

  At 90 days and at 180 days

• In healthy volunteers, determine the concentration of myo-inositol in brain (μmol/g)

  90 Days After Enrollment

Study Arms (1)

N-acetylcysteine

EXPERIMENTAL

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).

Drug: N-acetylcysteine

Interventions

N-acetylcysteine DRUG

1800mg NAC twice daily (3600mg/day) orally for approximately 90 days.

Also known as: PharmaNAC

N-acetylcysteine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must be 18 years or older.
• All participants must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent.
• Individuals with GD1 who are medically stable for participation in the study in the opinion of the investigator.
• GD1 patients must be on a stable, specific ERT and/or SRT therapy at a specific dose (e.g. on a units/kg basis) for at least 2 years.
• GD1 patients who have had a change in therapy, i.e. a change in dose or switch from one drug to another, can be enrolled after at least 6 months have elapsed since the change and is considered stable in the opinion of the clinician providing care to the patient.
• Healthy subjects who will be frequency-matched for age.
• All participants must not have taken antioxidants coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study and during the course of the study.

You may not qualify if:

• Medically unstable conditions in any group as determined by the investigators.
• Concurrent disease; medical condition; or an extenuating circumstance that, in the opinion of the investigator, might compromise subject safety, study compliance, completion of the study, or the integrity of the data collected for the study.
• Women who are pregnant or lactating or of child-bearing age who are not using acceptable forms of contraception.
• History of asthma that is presently being treated.
• Patients enrolled in another interventional study.
• Allergy to N-acetylcysteine.
• Patients who cannot or are unwilling to have blood drawn.
• Inability to undergo MRI scanning, including but not limited to: unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs.
• Unable to adhere to study protocol for whatever reason.

Sponsors & Collaborators

• University of Minnesota: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Lysosomal Disease Network: collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

New York University

New York, New York, 10016, United States

Location

Related Publications (4)

• Zhou J, Coles LD, Kartha RV, Nash N, Mishra U, Lund TC, Cloyd JC. Intravenous Administration of Stable-Labeled N-Acetylcysteine Demonstrates an Indirect Mechanism for Boosting Glutathione and Improving Redox Status. J Pharm Sci. 2015 Aug;104(8):2619-26. doi: 10.1002/jps.24482. Epub 2015 Jun 5.

  PMID: 26052837 BACKGROUND

• Radtke KK, Coles LD, Mishra U, Orchard PJ, Holmay M, Cloyd JC. Interaction of N-acetylcysteine and cysteine in human plasma. J Pharm Sci. 2012 Dec;101(12):4653-9. doi: 10.1002/jps.23325. Epub 2012 Sep 27.

  PMID: 23018672 BACKGROUND

• Coles LD, Tuite PJ, Oz G, Mishra UR, Kartha RV, Sullivan KM, Cloyd JC, Terpstra M. Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress. J Clin Pharmacol. 2018 Feb;58(2):158-167. doi: 10.1002/jcph.1008. Epub 2017 Sep 22.

  PMID: 28940353 BACKGROUND

• Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Oz G, Cloyd JC, Tuite PJ. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Clin Neuropharmacol. 2013 Jul-Aug;36(4):103-6. doi: 10.1097/WNF.0b013e31829ae713.

  PMID: 23860343 RESULT

Related Links

• University of Minnesota - Twin Cities, one of the two locations of this study
• The National Institutes of Health's Rare Diseases Clinical Research Network, which funds the Lysosomal Disease Network
• Lysosomal Disease Network's page at Rare Diseases Clinical Research Network's site

MeSH Terms

Conditions

Gaucher Disease

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Reena V. Kartha, PharmD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: October 22, 2015
• Study Start: September 1, 2015
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2)