Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Condition: Parkinson Disease; Cerebrospinal Fluid
MeSH terms: Parkinson Disease
Intervention: N-Acetylcysteine; Lumbar Puncture; Fluoroscopy
Intervention description: Oral; 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).; If needed for lumbar puncture
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: 5-S-Cysteinyldopamine; Cerebrospinal Fluid; PARKINSONS DISEASE; MONOAMINE OXIDASE INHIBITOR

Summary:

      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.
    

Eligibility criteria:

        -  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