Oral N-acetylcysteine for the Treatment of Parkinson's Disease
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) 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 Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Oral N-acetylcysteine for the Treatment of Parkinson's Disease|
- GSH levels in brain and peripheral circulation in all subjects post-NAC administration [ Time Frame: Visit 1 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
single oral administration of NAC 75 mg/kg to 140 mg/kg
Single, oral administration of N-acetylcysteine 75 mg/kg to 140 mg/kg
Other Name: NAC
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. 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, oral 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) and control participants.
- Quantitate baseline plasma and red blood cell GSH concentrations in those with PD and controls; and characterize NAC and GSH pharmacokinetics after a single oral NAC administration.
- Quantitate brain GSH levels (as ascertained through MRS) in those with PD and controls at baseline and after a single oral NAC administration simultaneously with Aim 1.
- Construct a pharmacokinetic model to evaluate the relationship between peripheral (plasma and RBC) and central (brain) GSH measurements.
|Contact: Sarah Hilbert, MSfirstname.lastname@example.org|
|United States, Minnesota|
|University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Sarah Hilbert, MS 612-624-7745 email@example.com|
|Principal Investigator: Paul Tuite, MD|
|Principal Investigator: James Cloyd, PharmD|