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

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ClinicalTrials.gov Identifier: NCT02583672
Recruitment Status : Recruiting
First Posted : October 22, 2015
Last Update Posted : May 3, 2019
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
National Center for Advancing Translational Science (NCATS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Neurological Disorders and Stroke (NINDS)
Lysosomal Disease Network
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Tracking Information
First Submitted Date  ICMJE August 21, 2015
First Posted Date  ICMJE October 22, 2015
Last Update Posted Date May 3, 2019
Actual Study Start Date  ICMJE September 2015
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
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 Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02583672 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
  • 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 Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1)
Official Title  ICMJE 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 Description 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gaucher Disease Type 1
Intervention  ICMJE Drug: N-acetylcysteine
1800mg NAC twice daily (3600mg/day) orally for approximately 90 days.
Other Name: PharmaNAC
Study Arms  ICMJE Experimental: N-acetylcysteine
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).
Intervention: Drug: N-acetylcysteine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 20, 2015)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 31, 2021
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Reena V. Kartha, Ph.D. 612-626-2436 rvkartha@umn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02583672
Other Study ID Numbers  ICMJE LDN6722
U54NS065768 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management & Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.
Responsible Party University of Minnesota - Clinical and Translational Science Institute
Study Sponsor  ICMJE University of Minnesota - Clinical and Translational Science Institute
Collaborators  ICMJE
  • Rare Diseases Clinical Research Network
  • National Center for Advancing Translational Science (NCATS)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Lysosomal Disease Network
Investigators  ICMJE
Principal Investigator: Reena V. Kartha, PharmD University of Minnesota - Clinical and Translational Science Institute
PRS Account University of Minnesota - Clinical and Translational Science Institute
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP