Back to resultsRole of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1)
Primary Purpose
Gaucher Disease Type 1
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
N-acetylcysteine
Sponsored by
About this trial
This is an interventional treatment trial for Gaucher Disease Type 1 focused on measuring Gaucher Disease, GD1, N-acetylcysteine, glutathione, GSH
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- University of MinnesotaRecruiting
- New York UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
N-acetylcysteine
Arm Description
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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").
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.
Change in subjects with Gaucher disease type 1, in concentration of myo-inositol in brain (μmol/g)
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)
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)
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)
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)
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.
Full Information
NCT ID
NCT02583672
First Posted
August 21, 2015
Last Updated
December 15, 2022
Sponsor
University of Minnesota
Collaborators
Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke (NINDS), Lysosomal Disease Network
1. Study Identification
Unique Protocol Identification Number
NCT02583672
Brief Title
Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1)
Official Title
Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1): Potential Use of Antioxidant/Anti-inflammatory Medications
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 2015 (Actual)
Primary Completion Date
July 31, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke (NINDS), Lysosomal Disease Network
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher Disease Type 1
Keywords
Gaucher Disease, GD1, N-acetylcysteine, glutathione, GSH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
N-acetylcysteine
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
N-acetylcysteine
Other Intervention Name(s)
PharmaNAC
Intervention Description
1800mg NAC twice daily (3600mg/day) orally for approximately 90 days.
Primary Outcome Measure Information:
Title
Change in subjects with Gaucher disease type 1, in concentration of glutathione in brain (μmol/g)
Description
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 Outcome Measure Information:
Title
In healthy volunteers, determination of level of glutathione in brain (μmol/g)
Description
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
Title
Change in subjects with Gaucher disease type 1, in concentration of glutathione in blood (μmol/g)
Description
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
Title
Change in healthy volunteers, in concentration of glutathione in blood (μmol/g)
Description
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.
Time Frame
Baseline, 45 days, and 90 days
Title
Change in subjects with Gaucher disease type 1, in concentration of myo-inositol in brain (μmol/g)
Description
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.
Time Frame
At 90 days and at 180 days
Title
In healthy volunteers, determine the concentration of myo-inositol in brain (μmol/g)
Description
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.
Time Frame
90 Days After Enrollment
Title
Change in subjects with Gaucher disease type 1, in concentration of TNF-alpha in plasma (pg/mL)
Description
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.
Time Frame
Baseline, 45 days, 90 days, 120 days, 150 days, 180 days, and 270 days
Title
Change in healthy volunteers, in concentration of TNF-alpha in plasma (pg/mL)
Description
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.
Time Frame
Baseline, 45 days, and 90 days
Title
Change in subjects with Gaucher disease type 1, in concentration of N-acetylcysteine (NAC) in blood (µg/ml)
Description
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.
Time Frame
120 days, 150 days, and 180 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reena V. Kartha, Ph.D.
Phone
612-626-2436
Email
rvkartha@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reena V. Kartha, PharmD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reena V. Kartha, PhD
Phone
612-626-2436
Email
rvkartha@umn.edu
First Name & Middle Initial & Last Name & Degree
Reena V. Kartha, PhD
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Lau, MD
Phone
212-263-8344
Email
Heather.Lau@nyumc.org
First Name & Middle Initial & Last Name & Degree
Marissa Ferraris
Email
marissa.ferraris@nyumc.org
First Name & Middle Initial & Last Name & Degree
Heather Lau, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Citations:
PubMed Identifier
26052837
Citation
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.
Results Reference
background
PubMed Identifier
23018672
Citation
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.
Results Reference
background
PubMed Identifier
28940353
Citation
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.
Results Reference
background
PubMed Identifier
23860343
Citation
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.
Results Reference
result
Links:
URL
http://www.lysosomaldiseasenetwork.org/
Description
Lysosomal Disease Network, which funds this study
URL
https://twin-cities.umn.edu/
Description
University of Minnesota - Twin Cities, one of the two locations of this study
URL
https://www.rarediseasesnetwork.org/
Description
The National Institutes of Health's Rare Diseases Clinical Research Network, which funds the Lysosomal Disease Network
URL
https://www.rarediseasesnetwork.org/LDN/
Description
Lysosomal Disease Network's page at Rare Diseases Clinical Research Network's site
Learn more about this trial
Role of Oxidative Stress and Inflammation in Type 1 Gaucher Disease (GD1)
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