Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT02212678
• Recruitment Status: Completed
• First Posted: August 8, 2014
• Results First Posted: May 16, 2019
• Last Update Posted: May 16, 2019
• Sponsor: University of Minnesota
• Collaborator: Parkinson's Disease Society of the United Kingdom
• Information provided by (Responsible Party): University of Minnesota

Tracking Information

• First Submitted Date: August 4, 2014
• First Posted Date: August 8, 2014
• Results First Submitted Date: April 23, 2019
• Results First Posted Date: May 16, 2019
• Last Update Posted Date: May 16, 2019
• Study Start Date: September 2014
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 23, 2019)

Glutathione (GSH) Brain Levels [ Time Frame: pre-dose and after approximately 28 days of treatment ]

GSH levels in brain of all subjects at baseline and post-NAC (n-acetylcysteine) dosing as measured by magnetic resonance spectroscopy (MRS)

Original Primary Outcome Measures (submitted: August 7, 2014)

GSH brain levels [ Time Frame: pre-dose and after approximately 28 days of treatment ]

GSH levels in brain of all subjects at baseline and post-NAC dosing as measured by MRS

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: August 7, 2014)

• NAC clearance [ Time Frame: 8 hours after NAC dosing ]
  NAC concentrations will be measured prior to and after dosing to estimate NAC clearance
• GSH and GSH redox blood levels [ Time Frame: predose and after approximately 28 days of dosing ]
  GSH and GSH redox measurements will be made prior to dosing and after approximately 28 days of dosing
• NAC volume of distribution [ Time Frame: over 8 hrs after dosing ]
  NAC concentrations will be measured prior to and after dosing to estimate NAC volume of distribution

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease
• Official Title: Repeated-Dose Oral N-acetylcysteine for the Treatment of Parkinson's Disease
• Brief Summary: The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry.
• Detailed Description: The investigators are interested in evaluating the use of oral N-acetylcysteine (NAC) as therapy for Parkinson's Disease (PD) and measuring changes in brain and blood chemistry. The investigators' hypothesis is that repeated oral dosing of NAC will result in increased brain and red blood cell GSH concentrations in individuals with Parkinson's disease (PD) and healthy controls. The specific aims are to 1.) measure plasma and blood (red blood cell) glutathione (GSH) and ratio of reduced GSH to oxidized glutathione (GSSG) in individuals with PD and healthy controls at baseline and after four weeks of repeated high doses of oral NAC (6000 mg/day) and 2) measure cortical GSH levels (as ascertained through MRS) in those with PD and healthy controls at baseline and four weeks during repeated high doses of oral NAC (6000 mg/day) simultaneously with Aim 1. This study will combine information from a medical history, a physical examination, and disease rating scales with results obtained using Magnetic Resonance Spectroscopy (MRS) brain scans and pharmacokinetic studies from blood samples. This research will require 2 visits, one at baseline and one after approximately 28 days of therapy. Participants will provide their medical history during the first visit, and undergo a physical examination and rating scale each visit (duration: 1 hour). The first visit including the brain scans and blood collection will require approximately 3 hours of time. The brain scan and pharmacokinetic studies for the second visit will require approximately 8 hours of time. In total the second visit will take roughly 9 hours.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson Disease

Intervention

Drug: N-acetylcysteine capsule

N-acetylcysteine capsule

Other Name: NAC

Study Arms

Experimental: N-acetylcysteine

Subjects will be provided 6000 mg/day of N-acetylcysteine (capsule) to be divided into 2 equal daily doses and taken orally for approximately 28 days

Intervention: Drug: N-acetylcysteine capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 23, 2019): 8
• Original Estimated Enrollment (submitted: August 7, 2014): 9
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. All participants must be 18 years or older
2. All enrollees must understand and cooperate with requirements of the study in the opinion of the investigators and must be able to provide written informed consent
3. Individuals with medically stable Parkinson's disease (in the opinion of the investigator)
4. All participants must not have taken antioxidants NAC, glutathione, coenzyme Q-10, vitamin C, or vitamin E for 3 weeks prior to the study
5. Absence of dementia in all subjects

Exclusion Criteria:

1. Inability to undergo MRI scanning without sedation and other MRI counterindications, such as metal in the body (see section 7.3)
2. Medically unstable conditions as determined by the investigators
3. Pregnant or lactating or those women of child-bearing age that are not using acceptable forms of contraception
4. Diagnosis of asthma that is presently being treated with any medication, or past history of asthma/bronchospasm resulting in an emergency room visit, hospitalization or treatment
5. Unable to adhere to study protocol for whatever reason

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02212678
• Other Study ID Numbers: 1406M51207; 123269 ( Other Identifier: FDA )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Minnesota
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Minnesota
• Original Study Sponsor: Same as current
• Collaborators: Parkinson's Disease Society of the United Kingdom

Investigators

• Principal Investigator: Paul Tuite, MD; University of Minnesota
• Principal Investigator: Lisa Coles, PhD; University of Minnesota

• PRS Account: University of Minnesota
• Verification Date: April 2019