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

November 1, 2021 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

Background:

Parkinsons 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 were diagnosed within the past 5 years. They must be taking a monoamine oxidase inhibitor.

Healthy volunteer participants ages 18 and older.

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, participants will have blood and urine tests. For several hours, they cannot eat or drink anything but water and their medications. Late in the morning they will have a meal.

About 2 hours later they will have a spinal tap (lumbar puncture). 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 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.

Healthy Volunteer (HV) participants will receive a spinal tap on day one, followed by a second spinal tap 48 hours after the first spinal tap. HV participants will not receive NAC.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Parkinsons disease (PD).

Study population:

The study population comprises up to 35 participants with early (less than or equal to 5 years from diagnosis), mild, levodopa-untreated PD and up to 6 healthy volunteer participants. The PD participants will be on an inhibitor of monoamine oxidase (MAO) that is prescribed for their disease.

Design:

The study has a two groups employing a pretest-posttest design. Each participant 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. For PD participants, the second LP is done after the participant 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. For HV participants the second LP takes place approximately 48 hours after the first LP.

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

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy Volunteers
HVs who undergo 2 LPs as inpatients, with 48 hours between LPs and no NAC treatment
Procedure: Lumbar Puncture
Each participant undergoes a baseline lumbar puncture (LP 1) 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 (LP 2) is completed after the PD participant has taken at least 5 doses of NAC (2 grams orally twice per day) and approximately 2 hours after the last NAC dose. For the HV participant, LP 2 occurs approximately 48 hours after LP 1 (no NAC administered).
Radiation: Fluoroscopy
If needed for lumbar puncture
Experimental: PD Patients
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).
Procedure: Lumbar Puncture
Each participant undergoes a baseline lumbar puncture (LP 1) 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 (LP 2) is completed after the PD participant has taken at least 5 doses of NAC (2 grams orally twice per day) and approximately 2 hours after the last NAC dose. For the HV participant, LP 2 occurs approximately 48 hours after LP 1 (no NAC administered).
Radiation: Fluoroscopy
If needed for lumbar puncture
Drug: N-Acetylcysteine
Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Mean Percent Change in Cerebrospinal Fluid (CSF) Concentration of 5-S-cysteinyl-dopamine (Cys-DA) Pre and Post-N-acetylcysteine (NAC) Treatment
Time Frame: All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.
Patients with Parkinson's Disease (PD) who took N-acetylcysteine (NAC), and healthy volunteers who did not take NAC, each had two separate lumbar punctures (LP 1 and LP 2) to obtain spinal fluid. The spinal fluid samples were used to measure the amount of a brain chemical called 5-S-cysteinyl-dopamine (Cys-DA). The primary outcome measure is the mean change in CSF Cys-DA levels between pre and post-NAC treatment, which is calculated as the difference of CSF Cys-DA levels at pre-treatment (LP 1) and post-treatment (LP 2) divided by CSF Cys-DA at pre-treatment (LP 1). A greater percent decrease in Cys-DA levels in the brain would suggest that NAC may contribute to a reduction in the oxidation of brain dopamine, while a smaller percent decrease would suggest that NAC had no effect on the oxidation of brain dopamine.
All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Ratio of Cys-DA/DOPAC Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Time Frame: All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.
Patients with Parkinson's Disease (PD) who took N-acetylcysteine (NAC), and healthy volunteers who did not take NAC, each had two separate lumbar punctures (LPs) to obtain spinal fluid. The spinal fluid samples were used to measure the ratio of the brain chemical called 5-S-cysteinyl-dopamine (Cys-DA) to the brain chemical called 3,4-Dihydroxyphenylacetic acid (Cys-DOPAC). Dopamine has 2 possible metabolic fates or processes of degradation. One fate is the breakdown of Dopamine by an enzyme to form DOPAC. The other fate is spontaneous oxidation to form Cys-DA. The ratio of Cys-DA to DOPAC may reflect these relative fates. If NAC reduced spontaneous oxidation to Cys-DA, then the ratio Cys-DA/DOPAC ratio would decrease between LP 1 and LP 2.
All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.
Mean Percent Change in Cys-DA/DOPAC Between Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Time Frame: All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.
Patients with Parkinson's Disease (PD) who took N-acetylcysteine (NAC), and healthy volunteers who did not take NAC, each had two separate lumbar punctures (LPs) to obtain spinal fluid. The spinal fluid samples were used to measure the ratio of the brain chemical called 5-S-cysteinyl-dopamine (Cys-DA) to the brain chemical called 3,4-Dihydroxyphenylacetic acid (Cys-DOPAC). Dopamine has 2 metabolic fates. One is the breakdown of dopamine by an enzyme to form DOPAC. The other is spontaneous oxidation to form Cys-DA. The ratio of Cys-DA/DOPAC may reflect these relative fates. If NAC reduced spontaneous oxidation to Cys-DA, then the ratio Cys-DA/DOPAC would decrease between LP 1 and LP 2, which would be reflected as a percent decrease.
All participants underwent a baseline LP. For PD participants, the second LP occurred approximately 2 hours after the participant had taken NAC the last NAC dose. For HV participants the second LP takes place approximately 48 hours after the first LP.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2017

Primary Completion (Actual)

February 27, 2020

Study Completion (Actual)

February 27, 2020

Study Registration Dates

First Submitted

April 4, 2017

First Submitted That Met QC Criteria

April 4, 2017

First Posted (Actual)

April 7, 2017

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

November 1, 2021

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 170076
  • 17-N-0076

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Parkinson Disease

Clinical Trials on Lumbar Puncture

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Suriname

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe