NCT03104725

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

Terminated Phase 1 Results posted Last updated 4 November 2021

What this trial tests

Phase 1 trial testing N-Acetylcysteine in Parkinson Disease in 6 participants. Terminated before completion.

Timeline

25 September 2017

Primary endpoint
27 February 2020

27 February 2020

Quick facts

Lead sponsor	National Institute of Neurological Disorders and Stroke (NINDS)
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	6
Start date	25 September 2017
Primary completion	27 February 2020
Estimated completion	27 February 2020
Sites	1 location across United States

Drugs / interventions tested

• N-Acetylcysteine — full drug profile →
• Lumbar Puncture — full drug profile →
• Fluoroscopy

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →
• Cerebrospinal Fluid — all drugs for Cerebrospinal Fluid →

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Who can join

18 and older, any sex, with Parkinson Disease or Cerebrospinal Fluid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Healthy Volunteers (HVs)	45.7	± 28.1
Parkinson's Disease (PD) Patients	20.1	± 14.2

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

Cys-DA/DOPAC LP1

Group	Value	95% CI
Healthy Volunteers (HVs)	0.12	± 0.05
Parkinson's Disease (PD) Patients	0.16	± 0.10

Cys-DA/DOPAC LP2

Group	Value	95% CI
Healthy Volunteers (HVs)	0.05	± 0.01
Parkinson's Disease (PD) Patients	0.13	± 0.08

Mean Percent Change in Cys-DA/DOPAC Between Pre and Post-treatment Lumbar Puncture With and Without N-acetylcysteine (NAC) Secondary · 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 spont

Group	Value	95% CI
Healthy Volunteers (HVs)	50.1	± 16.2
Parkinson's Disease (PD) Patients	27.2	± 5.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Duration of participation in study and up to 8 days following the second LP. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Healthy Volunteers (HVs)

Serious: 0/2 (0%)

Deaths: 0/2

Parkinson's Disease (PD) Patients

Serious: 0/4 (0%)

Deaths: 0/4

Other adverse events (4 terms — click to expand)

Reaction	System	Healthy Volunteers (HVs)	Parkinson's Disease (PD) P…
Puncture site pain	General disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Headache	Nervous system disorders	—	—
Paresthesia	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT03104725 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Overview on the Effects of <i>N</i>-Acetylcysteine in Neurodegenerative Diseases.
   Tardiolo G, Bramanti P, Mazzon E. · · 2018 · cited 197× · PMID 30551603 · DOI 10.3390/molecules23123305
2. Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?
   Leathem A, Ortiz-Cerda T, Dennis JM, Witting PK. · · 2022 · cited 25× · PMID 35805928 · DOI 10.3390/ijms23136923
3. Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.
   Aregawi L, Walitt B, Sullivan P, Norato G, et al · · 2026 · PMID 42205163 · DOI 10.1093/braincomms/fcag173