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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1): Potential Use of Antioxidant/Anti-inflammatory Medications

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.

Detailed Summary: 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.
Sponsor: University of Minnesota - Clinical and Translational Science Institute

Current Primary Outcome: Change in subjects with Gaucher disease type 1, in concentration of glutathione in brain (μmol/g) [ Time Frame: At 90 days and at 180 days ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • In healthy volunteers, determination of level of glutathione in brain (μmol/g) [ Time Frame: 90 Days After Enrollment ]
    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.
  • Change in subjects with Gaucher disease type 1, in concentration of glutathione in blood (μmol/g) [ Time Frame: Baseline, 45 days, 90 days, 120 days, 150 days, 180 days, and 270 days ]
    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").
  • Change in healthy volunteers, in concentration of glutathione in blood (μmol/g) [ Time Frame: Baseline, 45 days, and 90 days ]
    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.
  • Change in subjects with Gaucher disease type 1, in concentration of myo-inositol in brain (μmol/g) [ Time Frame: At 90 days and at 180 days ]
    The investigators will measure the concentration of myo-inositol in 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 MRS. The MRS study will take place over approximately 1.0 hour and will generate measurements of myo-inositol levels from 2-3 brain regions. Scanning may be done in multiple sessions if needed, but will not exceed 1.5 total scanning hours. These measures will be performed concurrently during the MRS scans being performed to measure GSH levels.
  • In healthy volunteers, determine the concentration of myo-inositol in brain (μmol/g) [ Time Frame: 90 Days After Enrollment ]
    The investigators will measure the concentration of myo-inositol in 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 myo-inositol levels from 2-3 brain regions. Scanning may be done in multiple sessions if needed, but will not exceed 1.5 total scanning hours. This measure will be performed concurrently during the MRS scan being performed to measure GSH level.
  • Change in subjects with Gaucher disease type 1, in concentration of TNF-alpha in plasma (pg/mL) [ Time Frame: Baseline, 45 days, 90 days, 120 days, 150 days, 180 days, and 270 days ]
    The investigators will measure the concentration of TNF-alpha in 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 immunoassay for TNF-alpha.
  • Change in healthy volunteers, in concentration of TNF-alpha in plasma (pg/mL) [ Time Frame: Baseline, 45 days, and 90 days ]
    The investigators will measure the concentration of TNF-alpha in blood of healthy volunteers at baseline (enrollment), at 45 days, and at 90 days. Blood samples will be drawn and analyzed using immunoassay for TNF-alpha.
  • Change in subjects with Gaucher disease type 1, in concentration of N-acetylcysteine (NAC) in blood (µg/ml) [ Time Frame: 120 days, 150 days, and 180 days ]
    Investigators will measure NAC levels in the blood of subjects with Gaucher disease type 1, at 120 days after enrollment, 150 days, and 180 days. Blood samples will be drawn and analyzed using LC-MS.


Original Secondary Outcome: Same as current

Information By: University of Minnesota - Clinical and Translational Science Institute

Dates:
Date Received: August 21, 2015
Date Started: September 2015
Date Completion: July 31, 2020
Last Updated: May 11, 2017
Last Verified: May 2017