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

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT03104725
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 29.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease; Cerebrospinal Fluid	Drug: N-Acetylcysteine; Procedure: Lumbar Puncture; Radiation: Fluoroscopy	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
• Actual Study Start Date: Sep 25, 2017
• Actual Primary Completion Date: Feb 27, 2020
• Actual Study Completion Date: Feb 27, 2020

Arms and Interventions

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).	Drug: N-Acetylcysteine; Oral; 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

Outcome Measures

Primary Outcome Measures

1. The Mean Percent Change in Cerebrospinal Fluid (CSF) Concentration of 5-S-cysteinyl-dopamine (Cys-DA) Pre and Post-N-acetylcysteine (NAC) Treatment [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.

Secondary Outcome Measures

1. Mean Ratio of Cys-DA/DOPAC Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC) [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.

2. Mean Percent Change in Cys-DA/DOPAC Between Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: David S Goldstein, M.D., National Institute of Neurological Disorders and Stroke (NINDS)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 11, 2019

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Goldstein DS, Holmes C, Sullivan P, Jinsmaa Y, Kopin IJ, Sharabi Y. Elevated cerebrospinal fluid ratios of cysteinyl-dopamine/3,4-dihydroxyphenylacetic acid in parkinsonian synucleinopathies. Parkinsonism Relat Disord. 2016 Oct;31:79-86. doi: 10.1016/j.parkreldis.2016.07.009. Epub 2016 Jul 20.
• Goldstein DS, Jinsmaa Y, Sullivan P, Holmes C, Kopin IJ, Sharabi Y. Comparison of Monoamine Oxidase Inhibitors in Decreasing Production of the Autotoxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde in PC12 Cells. J Pharmacol Exp Ther. 2016 Feb;356(2):483-92. doi: 10.1124/jpet.115.230201. Epub 2015 Nov 16.
• Goldstein DS, Kopin IJ, Sharabi Y. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson disease and related disorders. Pharmacol Ther. 2014 Dec;144(3):268-82. doi: 10.1016/j.pharmthera.2014.06.006. Epub 2014 Jun 16. Review.

• Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
• ClinicalTrials.gov Identifier: NCT03104725
• Other Study ID Numbers: 170076; 17-N-0076
• First Posted: Apr 7, 2017
• Last Update Posted: Nov 4, 2021
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS): 5-S-Cysteinyldopamine; Cerebrospinal Fluid; PARKINSONS DISEASE; MONOAMINE OXIDASE INHIBITOR
• Additional relevant MeSH terms: Parkinson Disease; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Recruitment Details	Participants with Parkinson's disease were recruited from the NINDS Parkinsons Clinic and the Patient Recruitment and Public Liaison Office (PRPL). Healthy participants were recruited from the PRPL.
Pre-assignment Detail	All participants were screened for eligibility. Eligible participants with PD underwent a baseline LP (LP 1), followed by administration of NAC, followed by post-treatment LP (LP 2). Healthy Volunteer participants underwent a baseline LP (LP 1) and follow-up LP (LP 2) 48 hours after the baseline LP.

Arm/Group Title	Healthy Volunteers (HVs)	Parkinson's Disease (PD) Patients
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.	PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).
Period Title: Overall Study
STARTED	2	4
COMPLETED	2	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Healthy Volunteers	Parkinson's Disease (PD) Patients	Total
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.	PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).	Total of all reporting groups
Overall Participants	2	4	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	2 50%	4 66.7%
>=65 years	0 0%	2 50%	2 33.3%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.5 (11.7)	65.6 (9.7)	59.5 (11.9)
Sex: Female, Male (Count of Participants)
Female	1 50%	2 50%	3 50%
Male	1 50%	2 50%	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	3 75%	5 83.3%
Unknown or Not Reported	0 0%	1 25%	1 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	3 75%	5 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 25%	1 16.7%

Outcome Measures

1. Primary Outcome

Title	The Mean Percent Change in Cerebrospinal Fluid (CSF) Concentration of 5-S-cysteinyl-dopamine (Cys-DA) Pre and Post-N-acetylcysteine (NAC) Treatment
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Volunteers (HVs)	Parkinson's Disease (PD) Patients
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.	PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).
Measure Participants	2	4
Mean (Standard Error) [percent change]	45.7 (28.1)	20.1 (14.2)

2. Secondary Outcome

Title	Mean Ratio of Cys-DA/DOPAC Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Volunteers (HVs)	Parkinson's Disease (PD) Patients
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.	PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).
Measure Participants	2	4
Cys-DA/DOPAC LP1	0.12 (0.05)	0.16 (0.10)
Cys-DA/DOPAC LP2	0.05 (0.01)	0.13 (0.08)

3. Secondary Outcome

Title	Mean Percent Change in Cys-DA/DOPAC Between Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Description	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.
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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Healthy Volunteers (HVs)	Parkinson's Disease (PD) Patients
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.	PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).
Measure Participants	2	4
Mean (Standard Error) [percent change]	50.1 (16.2)	27.2 (5.0)

Adverse Events

Time Frame	Duration of participation in study and up to 8 days following the second LP
Arm/Group Title	Healthy Volunteers (HVs)		Parkinson's Disease (PD) Patients
Arm/Group Description	HV participants undergo 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 within 48 hours of LP 1. No NAC treatment is administered.		PD participants undergo 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 patient has taken at least 5 doses of N-Acetylcysteine (NAC) (2 grams orally twice per day).
All Cause Mortality
	Healthy Volunteers (HVs)		Parkinson's Disease (PD) Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Serious Adverse Events
	Healthy Volunteers (HVs)		Parkinson's Disease (PD) Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Volunteers (HVs)		Parkinson's Disease (PD) Patients
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		1/4 (25%)
General disorders
Puncture site pain	2/2 (100%)	2	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/2 (50%)	1	0/4 (0%)	0
Nervous system disorders
Headache	0/2 (0%)	0	1/4 (25%)	1
Paresthesia	1/2 (50%)	1	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.