N-Acetylcysteine for Neuroprotection in Parkinson's Disease

NCT ID: NCT01470027

Last Updated: 2018-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2016-08-31

Brief 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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

N-acetylcysteine 1800mg

N-acetylcysteine 1800mg/day for 30 days

Group Type: ACTIVE_COMPARATOR

N-acetylcysteine

Intervention Type: DRUG

900mg NAC effervescent tablets

N-acetylcysteine 3600mg

N-acetylcysteine 3600mg daily for 30 days

Group Type: ACTIVE_COMPARATOR

N-acetylcysteine

Intervention Type: DRUG

900mg NAC effervescent tablets

Placebo

Placebo effervescent tablets daily for 30 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

effervescent tablets

Interventions

N-acetylcysteine

900mg NAC effervescent tablets

Intervention Type: DRUG

Placebo

effervescent tablets

Intervention Type: DRUG

Other Intervention Names

NAC

Eligibility 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dikoma C. Shungu, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Other Identifiers

1R21AG041509

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1109011912

Identifier Type: -

Identifier Source: org_study_id