N-Acetylcysteine for Neuroprotection in Parkinson's Disease

Condition(s) targeted: Parkinson Disease

Intervention: N-acetylcysteine (Drug); Placebo (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Weill Medical College of Cornell University

Official(s) and/or principal investigator(s):
Dikoma C. Shungu, Ph.D., Principal Investigator, Affiliation: Weill Medical College of Cornell University

Overall contact:
Claire Henchcliffe, MD DPhil, Phone: 212-746, Ext: 2584, Email: clh2007@med.cornell.edu

The overall objective of this developmental/exploratory study is to use noninvasive proton magnetic resonance spectroscopy (1H MRS) to determine (a) whether levels of the antioxidant glutathione (GSH) are decreased in vivo, as has been found in postmortem brain, in the brain of 30 patients with Parkinson's disease (PD) compared to matched controls; (b) whether GSH levels in PD brain increase significantly following 30 days of daily supplementation with 1800mg or 3600mg of N-acetylcysteine (NAC) compared to placebo and to baseline, and (c) whether any such increases in brain GSH would be dose-dependent and be associated with a change in the participants' oxidative stress profiles. In addition, a clinical assessment battery, including quantitative tests of motor function, will be performed to investigate potential associations between the NAC intervention, brain GSH levels, oxidative stress markers, and clinical presentation. If successful, this study will represent the first objective documentation of whether there is a GSH deficit in living PD brain that dietary NAC supplementation can mitigate, thereby providing a compelling justification for investigating such neuroprotective strategies in larger controlled clinical trials.

Official title: N-Acetylcysteine for Neuroprotection in Parkinson's Disease

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: change of cerebral glutathione levels as measured by proton magnetic resonance spectroscopy

Secondary outcome:

Unified Parkinson's Disease Rating Scale Parts I-V

Neuropsychiatric Inventory Questionnaire

Hamilton Depression Rating Scale (HAM-D)

9-Hole Peg Board Test

10-Meter Walk Test

oxidative stress markers in cerebrospinal fluid

Questionnaire for Impulsive Compulsive Disorders in PD

Beck Anxiety Inventory

PD quality of life questionnaire

Minimum age: 50 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of idiopathic PD according to the United Kingdom Parkinson's Disease

Society Brain Bank criteria (UKPDSBB) criteria (only for PD group

- Age 50 to 75 years

- Able to give informed consent for study participation

- Not on any medication for PD (anticholinergic agents allowed)

Exclusion Criteria:

- Unable to give informed consent

- Unable to undergo a brain MRI

- PD duration ≥15 years

- Receiving dopamine receptor blocking agents, including typical neuroleptics,

prochlorperazine, and metoclopramide

- Diagnosis of major depression or other axis I psychopathology

- Modified Mini-Mental Status Exam (MMSE) ≤ 24/30

- Diagnosis of chronic or persistent illnesses that could affect oxidative stress

status, such as diabetes or congestive heart failure

- Significant concomitant medical disease limiting life expectancy to less than 12

months from study inclusion

- Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or

other neurodegenerative diseases such as Alzheimer's disease or ALS

Claire Henchcliffe, MD DPhil, Phone: 212-746, Ext: 2584, Email: clh2007@med.cornell.edu

Weill Cornell Medical College, New York, New York 10021, United States; Recruiting
Dikoma C. Shungu, Ph.D., Principal Investigator
Claire Henchcliffe, MD DPhil, Sub-Investigator
Xiangling Mao, MS, Sub-Investigator
Nora Weiduschat, MD MPH, Principal Investigator
Halinder Mangat, MD, Sub-Investigator

Starting date: January 2012
Last updated: January 20, 2012