N-Acetylcysteine for Neuroprotection in Parkinson's Disease

NCT01470027 | Completed Phase 1 Results

• 2 other identifiers: 11090119121R21AG041509
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Keywords

magnetic resonance spectroscopy; N-acetylcysteine; antioxidant; glutathione

Outcome Measures

Primary Outcomes (1)

• Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy

  In vivo brain GSH measured with 1H MRS in the unmedicated patients with idiopathic PD and in sex- and age-matched healthy controls prior to and following 4 weeks supplementation with either placebo, 1800mg/day or 3600 mg/day of NAC. Striatal and occipital cortex glutathione levels as measured in vivo by 1H MRS at baseline and following 4 weeks of treatment with placebo, 1800mg NAC/day and 3600mg NAC/day. The area under the GSH spectral peak was obtained by frequency-domain fitting of the GSH resonance in the edited spectrum to a pseudo-Voigt lineshape function using a robust and highly optimized public-domain Levenberg-Marquardt nonlinear least-squares minimization routine. The resulting peak areas were then expressed as ratios relative to the synchronously acquired and similarly fitted unsuppressed voxel water signal.

  at baseline and 4 weeks after intervention start

Secondary Outcomes (7)

• Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported)

  at baseline and 4 weeks after intervention start

• Mini Mental State Examination (MMSE)

  at baseline and 4 weeks after intervention start

• Hamilton Depression Rating Scale (HAM-D)

  at baseline and 4 weeks after intervention start

• 9-Hole Peg Board Test (9-HPT)

  at baseline and 4 weeks after intervention start

• 10-Meter Walk Test

  at baseline and 4 weeks after intervention start

Study Arms (3)

N-acetylcysteine 1800mg

ACTIVE COMPARATOR

N-acetylcysteine 1800mg/day for 30 days

Drug: N-acetylcysteine

N-acetylcysteine 3600mg

ACTIVE COMPARATOR

N-acetylcysteine 3600mg daily for 30 days

Drug: N-acetylcysteine

Placebo

PLACEBO COMPARATOR

Placebo effervescent tablets daily for 30 days

Drug: Placebo

Interventions

N-acetylcysteine DRUG

900mg NAC effervescent tablets

Also known as: NAC

N-acetylcysteine 1800mg; N-acetylcysteine 3600mg

Placebo DRUG

effervescent tablets

Placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease or ALS

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

This study was limited by recruitment challenges related to identifying sufficient numbers of patients with PD who met all the eligibility criteria, especially with respect to medication status, and were willing to enter into the 4-week trial.

Results Point of Contact

• Title: Dr. Dikoma C. Shungu, Professor of Physics in Radiology
• Organization: Weill Cornell Medicine

dcs7001@med.cornell.edu

2127462481

Study Officials

• Dikoma C. Shungu, Ph.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 10, 2011
• Study Start: January 1, 2012
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 28, 2018
• Results First Posted: April 18, 2018

Record last verified: 2018-07

Locations

US (1)