Intravenous N-acetylcysteine for the Treatment of Gaucher's Disease and Parkinson's Disease

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT01427517
• Collaborator: Rare Diseases Clinical Research Network (Other), National Center for Advancing Translational Science (NCATS) (NIH), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 9
• Location: 1
• Arms: 3
• Duration (Months): 17.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The investigators are interested in determining if the investigators are able to detect changes in brain chemistry using Magnetic Resonance Spectroscopy (MRS) in individuals with Parkinson's disease (PD), those with Gaucher's disease (GD), and those without neurological disorders (healthy controls) when they are given the antioxidant N-acetylcysteine (NAC). This study will combine information from a medical history, a physical examination and disease rating scales with results obtained using MRS brain scans and pharmacokinetic studies from blood samples. This research will require 1 visit that will require about 4 to 5 hours of time. During this study, participants will provide their medical history, be examined and undergo a rating scale for about one hour; the brain scan and pharmacokinetic studies will require 1.5-2 hours of time; in total the study will take about 4-5 hours.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease; Gaucher's Disease	Drug: N-acetylcysteine	Phase 1

Detailed Description

Oxidative stress is implicated in the pathogenesis of a number of neurodegenerative diseases such as Parkinson's disease (PD). Further, levels of glutathione (GSH), a prevalent endogenous antioxidant, are decreased in the postmortem substantia nigra (SN) of individuals with PD, indicating increased oxidative stress, although this has yet not been confirmed in vivo. Increases in intracellular oxidative stress have also been observed in primary fibroblast cultures obtained from patients with GD, where enzyme replacement therapy resulted in increases in total GSH. The hypothesis that oxidative stress plays a key role in the neurodegeneration associated with PD suggests that antioxidants may be useful in altering disease progression.

N-acetylcysteine (NAC) is a well-known antioxidant that is thought to act both as a free radical scavenger and as a cysteine donor for the synthesis of GSH. NAC may be beneficial in the treatment of PD and GD. Magnetic resonance spectroscopy (MRS) methods may be able to determine if there are effects from NAC on central nervous system GSH levels. In addition, use of red blood cell (RBC) measurements of GSH, if correlated with brain concentrations, could serve as an easily measured biomarker to help characterize and monitor response to therapy. The investigators therefore propose to conduct a study of the effect of a single, intravenous dose of NAC on central (brain) measures of GSH and peripheral (RBC) measures of GSH in people with PD and healthy controls, through the use of simultaneous MRS techniques and pharmacokinetic studies. The investigators hypothesis and specific aims are as follows:

Hypothesis: RBC and brain GSH concentrations will increase following oral NAC administration in individuals with Parkinson's disease (PD), Gaucher's disease (GD), and control participants.

Specific Aims:

1. Quantitate baseline plasma and red blood cell GSH concentrations in those with PD and GD and controls; and characterize NAC and GSH pharmacokinetics after a single intravenous NAC administration.

2. Quantitate brain GSH levels (as ascertained through MRS) in those with PD and GD and controls at baseline and after a single intravenous NAC administration simultaneously with Aim 1.

3. Construct a pharmacokinetic model to evaluate the relationship between peripheral (plasma and RBC) and central (brain) GSH measurements.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intravenous N-acetylcysteine for the Treatment of Gaucher's Disease and Parkinson's Disease
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NAC in PD single intravenous administration of N-acetylcysteine in PD patients	Drug: N-acetylcysteine; Single, intravenous administration of N-acetylcysteine; Other Names: NAC
Experimental: NAC in GD single intravenous administration of N-acetylcysteine in GD patients	Drug: N-acetylcysteine; Single, intravenous administration of N-acetylcysteine; Other Names: NAC
Experimental: NAC in controls single intravenous administration of N-acetylcysteine in control subjects	Drug: N-acetylcysteine; Single, intravenous administration of N-acetylcysteine; Other Names: NAC

Outcome Measures

Primary Outcome Measures

1. Brain GSH [Baseline and up to 110 minutes post-NAC administration]

   change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. All participants must be 18 years or older.

2. All enrollees 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 medically stable Parkinson's disease (in the opinion of the investigator).

4. All participants must not have taken antioxidants coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study.

5. Absence of dementia in all subjects, as determined by pre-scanning cognitive assessment.

6. Control subjects who are able to undergo MRS

Exclusion Criteria:

1. Inability to undergo MRI scanning without sedation

2. Medically unstable conditions in any group as determined by the investigators

3. Pregnant or lactating or those women of child-bearing age that are not using acceptable forms of contraception

4. Diagnosis of asthma that is presently being treated with ANY medication, or past history of asthma/bronchospasm resulting in an emergency room visit, hospitalization or treatment

5. Unable to adhere to study protocol for whatever reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• University of Minnesota
• Rare Diseases Clinical Research Network
• National Center for Advancing Translational Science (NCATS)
• National Institute of Neurological Disorders and Stroke (NINDS)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Paul Tuite, MD, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT01427517
• Other Study ID Numbers: FWA00000312-2; U54NS065768
• First Posted: Sep 1, 2011
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by University of Minnesota: Parkinson's disease; Gaucher's disease; Control
• Additional relevant MeSH terms: Parkinson Disease; Gaucher Disease; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Recruitment Details	Subjects were primarily recruited from the investigators' clinics at the University of Minnesota, and from research volunteers signed up with the University's Center for Magnetic Resonance Research.
Pre-assignment Detail	Groups were not assigned in this study. All subjects received the same intervention.

Arm/Group Title	NAC in PD	NAC in GD	NAC in Controls
Arm/Group Description	single intravenous administration of N-acetylcysteine in PD patients	single intravenous administration of N-acetylcysteine in GD patients	single intravenous administration of N-acetylcysteine in control subjects
Period Title: Overall Study
STARTED	3	3	3
COMPLETED	3	3	3
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	NAC in PD	NAC in GD	NAC in Controls	Total
Arm/Group Description	single intravenous administration of N-acetylcysteine in PD patients	single intravenous administration of N-acetylcysteine in GD patients	single intravenous administration of N-acetylcysteine in control subjects	Total of all reporting groups
Overall Participants	3	3	3	9
Age (Count of Participants)
<=18 years	0 0%	1 33.3%	0 0%	1 11.1%
Between 18 and 65 years	3 100%	2 66.7%	3 100%	8 88.9%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.33 (3.21)	44 (23.58)	58 (0)	52.11 (13.46)
Sex: Female, Male (Count of Participants)
Female	3 100%	0 0%	2 66.7%	5 55.6%
Male	0 0%	3 100%	1 33.3%	4 44.4%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	3 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Brain GSH
Description	change in brain GSH levels from baseline to post-NAC administration (90 - 110 minutes) in all subjects
Time Frame	Baseline and up to 110 minutes post-NAC administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NAC in PD	NAC in GD	NAC in Controls
Arm/Group Description	single intravenous administration of N-acetylcysteine in PD patients	single intravenous administration of N-acetylcysteine in GD patients	single intravenous administration of N-acetylcysteine in control subjects
Measure Participants	3	3	3
Mean (Standard Deviation) [percent increase from baseline]	55 (24.4)	41 (16.3)	34 (19.8)

Adverse Events

Arm/Group Title	NAC in PD		NAC in GD		NAC in Controls
Arm/Group Description	single intravenous administration of N-acetylcysteine in PD patients		single intravenous administration of N-acetylcysteine in GD patients		single intravenous administration of N-acetylcysteine in control subjects
All Cause Mortality
	NAC in PD		NAC in GD		NAC in Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	NAC in PD		NAC in GD		NAC in Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	NAC in PD		NAC in GD		NAC in Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/3 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
allergic reaction	1/3 (33.3%)	1	0/3 (0%)	0	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.