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

October 30, 2019 updated by: University of Minnesota
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain GSH
Time Frame: 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
Baseline and up to 110 minutes post-NAC administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

August 30, 2011

First Submitted That Met QC Criteria

August 31, 2011

First Posted (Estimate)

September 1, 2011

Study Record Updates

Last Update Posted (Actual)

November 1, 2019

Last Update Submitted That Met QC Criteria

October 30, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FWA00000312-2
  • U54NS065768 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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