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Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?

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ClinicalTrials.gov Identifier: NCT03104725
Recruitment Status : Recruiting
First Posted : April 7, 2017
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
First Submitted Date  ICMJE April 4, 2017
First Posted Date  ICMJE April 7, 2017
Last Update Posted Date March 25, 2019
Actual Study Start Date  ICMJE September 25, 2017
Estimated Primary Completion Date January 4, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
More than or less than 10% decrease in cerebrospinal fluid level of 5-S-cysteinyldopamine [ Time Frame: CSF Cys-DA at pre-treatment CSF Cys-DA at posttreatment ]
The primary outcome measure is the relative change in CSF Cys-DA levels between pre and post-NAC treatment, which is calculated as: the difference of (CSF Cys-DA at pre-treatment CSF Cys-DA at post-treatment) divided by CSF Cys-DA at pre-treatment. The change will be dichotomized as decrease vs. no decrease with a threshold decrease to be determined based on the pilot study ofHVs.
Original Primary Outcome Measures  ICMJE
 (submitted: April 4, 2017)
More than or less than 10% decrease in cerebrospinal fluid level of 5-S-cysteinyldopamine [ Time Frame: 2 days ]
Change History Complete list of historical versions of study NCT03104725 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
  • Cerebrospinal fluid concentration of 5-S-cysteinyldopamine [ Time Frame: Pre- and post-treatment ]
    Neurochemistry
  • Cerebrospinal fluid concentrations of neurchemicals [ Time Frame: Pre- and post-treatment ]
    Neurochemistry
Original Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2017)
  • Cerebrospinal fluid concentration of 5-S-cysteinyldopamine [ Time Frame: 2 days ]
  • Cerebrospinal fluid concentrations of neurchemicals [ Time Frame: 2 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Official Title  ICMJE Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Brief Summary

Background:

Parkinson s disease (PD) causes slow movement, stiffness, and poor balance. Many symptoms are due to the loss of brain cells that make the brain chemical dopamine. The cells may be damaged by the breakdown of dopamine by a process called oxidation. The drug N-acetylcysteine (NAC) can act as an antioxidant. Researchers want to test if NAC can decrease the oxidation of brain dopamine in people with PD.

Objective:

To look at the effect of NAC on brain chemistry in people with PD.

Eligibility:

People ages 18 and older with PD that was diagnosed within the past 5 years. They must be taking a monoamine oxidase inhibitor.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Participants will be hospitalized for 4 to 8 days.

On day 1, they will have blood and urine tests. They cannot eat or drink anything but water and their medications for several hours. Late in the morning they will have a meal.

About 2 hours later they will have a spinal tap. For this, a numbing medicine is injected into the back. A needle is inserted between the bones in the back to remove a small amount of fluid. The spinal tap may be use x-rays to see inside the body.

After the spinal tap, they will start taking NAC by mouth.

They will take NAC twice a day for 2 more days.

On the next day, they will not eat until a meal in the late morning. They will take a final NAC dose.

About 2 hours later they will have a second spinal tap.

Detailed Description

Objective:

This study is to test whether N-acetylcysteine (NAC) inhibits the spontaneous oxidation of central neural dopamine as indicated by the cerebrospinal fluid (CSF) concentration of 5-S-cysteinyl-dopamine (Cys-DA) in patients with Parkinson s disease (PD).

Study population:

The study population comprises up to 35 patients with early (less than or equal to 5 years from diagnosis), mild, levodopa-untreated PD. The patients will be on an inhibitor of monoamine oxidase (MAO) that is prescribed for their disease.

Design:

The study has a one group, pretest-posttest design. Each patient undergoes a lumbar puncture (LP) as an inpatient at the NIH Clinical Center to obtain cerebrospinal fluid (CSF) for assays of Cys-DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and related biochemicals. The second LP is done after the patient has taken at least 5 doses of NAC (2 grams orally twice per day). The LP takes place about 2 hours after the last NAC dose.

Outcome measures:

The main outcome measure is the CSF concentration of Cys-DA. Other outcome measures are levels of other catecholamine-related neurochemicals or of indices of oxidative stress. Depending on the results, an exploratory study may be done involving NAC at 1 gram orally twice per day.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Parkinson Disease
Intervention  ICMJE
  • Drug: N-Acetylcysteine
    Oral
  • Procedure: Lumbar Puncture
    Each patient undergoes a lumbar puncture (LP) as an inpatient at the NIH Clinical Center to obtain cerebrospinal fluid (CSF) for assays of Cys-DA, 3,4- dihydroxyphenylacetic acid (DOPAC), and related biochemicals. The second LP is done after the patient has taken at least 5 doses of NAC (2 grams orally twice per day). The LP takes place about 2 hours after the last NAC dose.
  • Radiation: Fluoroscopy
    If needed for lumbar puncture
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 23, 2018)
41
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2017)
35
Estimated Study Completion Date  ICMJE January 4, 2021
Estimated Primary Completion Date January 4, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • PD diagnosed within the past 5 years
  • Taking a monoamine oxidase (MAO) inhibitor
  • Able to provide consent
  • At least18 years old

EXCLUSION CRITERIA:

  • Taking levodopa in any form
  • Known allergy to NAC
  • Already taking an anti-oxidant dietary supplement (e.g., Olive Leaf Extract, MitoQ)
  • A condition that would increase risk from a lumbar puncture (e.g., symptomatic spinal stenosis or myoclonus)
  • History of a post-spinal headache that required treatment with a blood patch
  • On a prescribed anti-coagulant (e.g., Coumadin, Plavix)
  • Pregnant or breast-feeding
  • History of alcohol or drug abuse
  • Any medical condition thatcould put subjects at increased risk. Potential participants are excluded who have evidence of bone marrow, liver, or kidney failure based on abnormal screening lab results.
  • On a medication that could interfere with the scientific results. An example of an exclusionary drug is the catechol-O-methyltransferase inhibitor entacapone. Tricyclic anti-depressants are another type of exclusionary drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Janna Gelsomino, R.N. (301) 435-5166 janna.gelsomino@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03104725
Other Study ID Numbers  ICMJE 170076
17-N-0076
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Study Sponsor  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David S Goldstein, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 14, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP