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

Phase 2RecruitingNCT02583672

University of Minnesota50 enrolled

Overview

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.

The investigators will also examine if there is a change in these blood and brain chemicals in GD1 patients after receiving oral N-acetylcysteine ("NAC"), which is available both as a prescription medication and as a dietary-supplement product, that has antioxidant and anti-inflammatory effects. Any changes the investigators may find in chemical levels may improve our understanding of the disease and could eventually lead to better treatment options. This is a multi-center study of approximately 50 people with Type 1 Gaucher disease (GD1) and healthy volunteers. Healthy volunteers will have 3 study visits over the course of 3 months. Procedures will include review of medical history, blood draws at each visit, and an MRI scan at the third visit. GD1 patients will have 7 study visits over the course of 9 months. Procedures include review of medical history, blood draws at each visit (multiple draws from an IV catheter at Visit 6), neurological exams, pain and fatigue questionnaires, and MRI scans (at Visits 3 and 6). In addition, GD1 patients will be given oral NAC at Visit 3, to begin taking twice a day for 90 days. All MRI scans will be done at the University of Minnesota in Minneapolis.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gaucher Disease Type 1

Interventions

N-acetylcysteineDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. All participants must be 18 years or older. 2. 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. 3. Individuals with GD1 who are medically stable for participation in the study in the opinion of the investigator. 4. 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. 5. 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. 6. Healthy subjects who will be frequency-matched for age. 7. 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. Exclusion Criteria: 1. Medically unstable conditions in any group as determined by the investigators. 2. 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. 3. Women who are pregnant or lactating or of child-bearing age who are not using acceptable forms of contraception. 4. History of asthma that is presently being treated. 5. Patients enrolled in another interventional study. 6. Allergy to N-acetylcysteine. 7. Patients who cannot or are unwilling to have blood drawn. 8. 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. 9. Unable to adhere to study protocol for whatever reason.

Locations (2)

University of Minnesota

Minneapolis, Minnesota, United States

RECRUITING

New York University

New York, New York, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: At 90 days and at 180 days

Secondary Outcomes

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

The investigators will measure the glutathione (GSH) level in the brains of healthy volunteers at 90 days after enrollment. This measure will be obtained using 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.

Time frame: 90 Days After Enrollment

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

Investigators will measure the glutathione concentration in the blood of subjects with Gaucher disease type 1, at baseline (enrollment), 45 days, 90 days, 120 days, 150 days, 180 days, and 270 days. Blood samples will be drawn and analyzed using liquid chromatography-tandem mass spectrometry ("LC-MS").

Time frame: 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)

Investigators will measure the concentration of glutathione in the blood of healthy volunteers at baseline, at 45 days, and at 90 days. Blood samples will be drawn and analyzed using LC-MS.

Central Contacts

Reena V. Kartha, Ph.D.

CONTACT

612-626-2436 rvkartha@umn.edu

Data from ClinicalTrials.gov

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