N-Acetylcysteine for Neuroprotection in Parkinson's Disease (NAC for PD)

• Unified Parkinson's Disease Rating Scale Parts I-V [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• Neuropsychiatric Inventory Questionnaire [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• Hamilton Depression Rating Scale (HAM-D) [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• 9-Hole Peg Board Test [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• 10-Meter Walk Test [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• oxidative stress markers in cerebrospinal fluid [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• Questionnaire for Impulsive Compulsive Disorders in PD [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• Beck Anxiety Inventory [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]
• PD quality of life questionnaire [ Time Frame: at baseline and 4 weeks after intervention start ] [ Designated as safety issue: No ]

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.

• Drug: N-acetylcysteine
  900mg NAC effervescent tablets
  Other Name: NAC
• Drug: Placebo
  effervescent tablets

• Active Comparator: N-acetylcysteine 1800mg
  N-acetylcysteine 1800mg/day for 30 days
  Intervention: Drug: N-acetylcysteine
• Active Comparator: N-acetylcysteine 3600mg
  N-acetylcysteine 3600mg daily for 30 days
  Intervention: Drug: N-acetylcysteine
• Placebo Comparator: Placebo
  Placebo effervescent tablets daily for 30 days
  Intervention: Drug: Placebo

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