Trial Outcomes & Findings for Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease? (NCT NCT03104725)
NCT ID: NCT03104725
Last Updated: 2021-11-04
Results Overview
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.
TERMINATED
PHASE1
6 participants
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.
2021-11-04
Participant Flow
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.
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.
Participant milestones
| Measure |
Healthy Volunteers (HVs)
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.
|
Parkinson's Disease (PD) Patients
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).
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|---|---|---|
|
Overall Study
STARTED
|
2
|
4
|
|
Overall Study
COMPLETED
|
2
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Does N-Acetylcysteine Decrease Spontaneous Oxidation of Central Neural Dopamine in Parkinson's Disease?
Baseline characteristics by cohort
| Measure |
Healthy Volunteers
n=2 Participants
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.
|
Parkinson's Disease (PD) Patients
n=4 Participants
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
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Age, Continuous
|
47.5 Years
STANDARD_DEVIATION 11.7 • n=93 Participants
|
65.6 Years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
59.5 Years
STANDARD_DEVIATION 11.9 • n=27 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Healthy Volunteers (HVs)
n=2 Participants
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.
|
Parkinson's Disease (PD) Patients
n=4 Participants
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).
|
|---|---|---|
|
The Mean Percent Change in Cerebrospinal Fluid (CSF) Concentration of 5-S-cysteinyl-dopamine (Cys-DA) Pre and Post-N-acetylcysteine (NAC) Treatment
|
45.7 percent change
Standard Error 28.1
|
20.1 percent change
Standard Error 14.2
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SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Healthy Volunteers (HVs)
n=2 Participants
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.
|
Parkinson's Disease (PD) Patients
n=4 Participants
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).
|
|---|---|---|
|
Mean Ratio of Cys-DA/DOPAC Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Cys-DA/DOPAC LP1
|
0.12 ratio
Standard Error 0.05
|
0.16 ratio
Standard Error 0.10
|
|
Mean Ratio of Cys-DA/DOPAC Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
Cys-DA/DOPAC LP2
|
0.05 ratio
Standard Error 0.01
|
0.13 ratio
Standard Error 0.08
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Healthy Volunteers (HVs)
n=2 Participants
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.
|
Parkinson's Disease (PD) Patients
n=4 Participants
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).
|
|---|---|---|
|
Mean Percent Change in Cys-DA/DOPAC Between Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC)
|
50.1 percent change
Standard Error 16.2
|
27.2 percent change
Standard Error 5.0
|
Adverse Events
Healthy Volunteers (HVs)
Parkinson's Disease (PD) Patients
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Volunteers (HVs)
n=2 participants at risk
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.
|
Parkinson's Disease (PD) Patients
n=4 participants at risk
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).
|
|---|---|---|
|
General disorders
Puncture site pain
|
100.0%
2/2 • Number of events 2 • Duration of participation in study and up to 8 days following the second LP
|
0.00%
0/4 • Duration of participation in study and up to 8 days following the second LP
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
50.0%
1/2 • Number of events 1 • Duration of participation in study and up to 8 days following the second LP
|
0.00%
0/4 • Duration of participation in study and up to 8 days following the second LP
|
|
Nervous system disorders
Headache
|
0.00%
0/2 • Duration of participation in study and up to 8 days following the second LP
|
25.0%
1/4 • Number of events 1 • Duration of participation in study and up to 8 days following the second LP
|
|
Nervous system disorders
Paresthesia
|
50.0%
1/2 • Number of events 1 • Duration of participation in study and up to 8 days following the second LP
|
0.00%
0/4 • Duration of participation in study and up to 8 days following the second LP
|
Additional Information
Dr. David Goldstein
National Institutes of Health/NINDS
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place