N-Acetylcysteine for Neuroprotection in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The overall objective of this developmental/exploratory study is to use noninvasive proton
      magnetic resonance spectroscopy (1H MRS) to assess (a) whether brain levels of the
      antioxidant glutathione (GSH) are decreased in vivo, as has been found in postmortem brain,
      in 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.
    

Detailed description: 
      Parkinson's disease (PD) is a neurodegenerative disorder in which deficits of the primary
      intracellular antioxidant, glutathione (GSH), are postulated to mediate increased oxidative
      stress and mitochondrial dysfunction in the pathogenic cascade leading up to the loss of
      nigrostriatal dopaminergic neurons that is the hallmark of the disorder. Therefore, there is
      currently great interest in treatment strategies that can maintain, restore and/or elevate
      intracellular GSH levels. However, GSH does not readily cross the blood-brain barrier or the
      membranes of most cells, including neurons, so that direct dietary supplementation of the
      antioxidant has not proved viable in increasing its intracellular concentration. On the other
      hand, since the bioavailability of cysteine, which does cross both the blood-brain barrier
      and most cell membranes, is rate-limiting in the GSH synthesis pathway, this amino acid and
      its non-toxic derivatives, such as N-acetylcysteine (NAC), are being investigated as
      potential precursors that can be supplied through dietary means to spur in situ synthesis and
      elevation of brain GSH. The overall objective of this Exploratory/Developmental (R21) study
      is to use noninvasive proton magnetic resonance spectroscopy (1H MRS) to determine (a)
      whether levels of GSH are decreased in vivo in the brain of 30 patients with Parkinson's
      disease (PD) compared to matched controls, as has been found in postmortem brain; (b) whether
      GSH levels in PD brain increase significantly following 30 days of daily supplementation with
      1800mg or 3600mg of NAC compared to baseline and placebo, 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. Additionally, 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.
    

Intervention name(s): N-acetylcysteine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 900mg NAC effervescent tablets; effervescent tablets
Other intervention name(s): NAC
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: magnetic resonance spectroscopy; N-acetylcysteine; antioxidant; glutathione