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Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

N-Acetylcysteine for Neuroprotection in Parkinson's Disease

Short name NAC for PD

NCTNCT01470027 (opens ClinicalTrials.gov in a new tab)Other id1109011912Other id1R21AG041509

This trial does not test a peptide that PepBank tracks.

  • Measures Glutathione, does not give it. It appears in an outcome measure.

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
50 participants (actual)
Sponsor
Weill Medical College of Cornell University · Other
Design
Randomized · Quadruple masking
Countries
1 country

United States

Start
Jan 2012
Primary completion
Aug 2016
Completion
Aug 2016
First posted
10 Nov 2011 (estimated)
Last update posted
28 Aug 2018
Conditions
Parkinson Disease

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201220132014201520162017
  1. Ph 1/2

    NAC for PD

    NCT01470027

    Jan 2012 to Aug 2016

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The overall objective of this developmental/exploratory study is to use noninvasive proton magnetic resonance spectroscopy (1H MRS) to assess (a) whether brain levels of the antioxidant glutathione (GSH) are decreased in vivo, as has been found in postmortem brain, in 30 patients with Parkinson's disease (PD) compared to matched controls; (b) whether GSH levels in PD brain increase significantly following 30 days of daily supplementation with 1800mg or 3600mg of N-acetylcysteine (NAC) compared to placebo and to baseline, and (c) whether any such increases in brain GSH would be dose-dependent and be associated with a change in the participants' oxidative stress profiles. In addition, a clinical assessment battery, including quantitative tests of motor function, will be performed to investigate potential associations between the NAC intervention, brain GSH levels, oxidative stress markers, and clinical presentation. If successful, this study will represent the first objective documentation of whether there is a GSH deficit in living PD brain that dietary NAC supplementation can mitigate, thereby providing a compelling justification for investigating such neuroprotective strategies in larger controlled clinical trials.

Interventions

  • N-acetylcysteineDrug
  • PlaceboDrug

Arms3

  • Active comparator

    N-acetylcysteine 1800mg

    N-acetylcysteine 1800mg/day for 30 days

  • Active comparator

    N-acetylcysteine 3600mg

    N-acetylcysteine 3600mg daily for 30 days

  • Placebo comparator

    Placebo

    Placebo effervescent tablets daily for 30 days

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    In vivo brain GSH measured with 1H MRS in the unmedicated patients with idiopathic PD and in sex- and age-matched healthy controls prior to and following 4 weeks supplementation with either placebo, 1800mg/day or 3600 mg/day of NAC. Striatal and occipital cortex glutathione levels as measured in vivo by 1H MRS at baseline and following 4 weeks of treatment with placebo, 1800mg NAC/day and 3600mg NAC/day. The area under the GSH spectral peak was obtained by frequency-domain fitting of the GSH resonance in the edited spectrum to a pseudo-Voigt lineshape function using a robust and highly optimized public-domain Levenberg-Marquardt nonlinear least-squares minimization routine. The resulting peak areas were then expressed as ratios relative to the synchronously acquired and similarly fitted unsuppressed voxel water signal.

Secondary outcomes(7)
  1. Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported)

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The UPDRS is considered the gold standard for determining disease severity and progression in patients with Parkinson's disease. It consists of the following five elements: 1. Evaluation of mentation, behavior and mood. 2. Self evaluation of the activities of daily living (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, etc. 3. Motor evaluation by a clinician. 4. Hoehn and Yahr scale (Hoehn 1967) for the description of the overall disease severity in PD with 8 stages. 5. Schwab and England activities of daily living scale (Schwab and England 1969) for the estimation of the general abilities in PD patients. The Schwab and England ADL scale is graduated in 10% steps with 100% indicating complete independence and 0% indicating an individual in whom the vegetative functions are completely impaired. A total of 199 points are possible for UPDRS, with 199 representing the worst disability and 0 no disability.

  2. Mini Mental State Examination (MMSE)

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The MMSE is a brief questionnaire-based test that is used to screen for cognitive impairment. Domains tested are orientation to time and place, registration, attention and calculation, recall, language, repetition and complex commands. Scores lower than 25/30 points indicate mild (21-24 points), moderate (10-20 points) or severe (\<10 points) cognitive impairment, but scores may need to be corrected for educational attainment, age and interfering impairments such as motor deficits that affect drawing skills.

  3. Hamilton Depression Rating Scale (HAM-D)

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The Hamilton Depression Rating Scale (HAM-D) is a 21-item instrument designed to measure the severity of illness in adults already diagnosed as having depression. The Hamilton Depression Rating Scale (HAM-D) has proven useful for many years as a way of determining a patient's level of depression before, during, and after treatment. It is clinician-administered and requires 15 to 20 minutes complete the interview and score the results. Although the HAM-D form lists 21 items, the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. The minimum score is 0 and maximum score is 50. The scale has been widely used in clinical practice and become a standard in pharmaceutical trials. HAM-D Scoring Instructions are following: 0-7 = Normal; 8-13 = Mild Depression; 14-18 = Moderate Depression; 19-22 = Severe Depression; ≥ 23 = Very Severe Depression.

  4. 9-Hole Peg Board Test (9-HPT)

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The 9-HPT is a standardized, quantitative timed test of upper extremity motor function. Individuals are asked to place and remove nine pegs, one at a time, from nine holes in a board as quickly as possible. The task is performed twice with the dominant and twice with the non-dominant hand, and the average time to complete the task once is calculated for each hand. The 9-HPT has a high inter- and intra-rater reliability, is validated and is sensitive to detect minor impairments of hand function.

  5. 10-Meter Walk Test

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The 10-meter walk test is a standardized, quantitative timed test of lower body motor function. The maximal gait speed is measured during a 10-meter walk. The task will be performed three times and the average time to complete the task once will be recorded. The 10-meter walk test is a reliable and sensitive measure of gait function in elderly individuals and PD patients. Cut-off values: \< 0.4 m/s more likely to be household ambulators; 0.4 - 0.8 m/s limited community ambulators; \> 0.8 m/s community ambulators.

  6. Beck Anxiety Inventory

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The Beck Anxiety Inventory (BAI) is a clinician-administered and validated instrument to discriminate anxiety from depression. The standardized BAI cutoffs are: 0-9: minimal anxiety; 10-16: mild anxiety; 17-29: moderate anxiety; 30-63: severe anxiety.

  7. Parkinson's Disease Quality of Life Questionnaire (PDQLQ)

    Time frame · at baseline and 4 weeks after intervention start

    Registry description

    The Parkinson's Disease Quality of Life Questionnaire is a self completion PRO designed to address aspects of functioning and well-being for those affected by Parkinson's disease. The Parkinson's Disease Quality of Life Questionnaire is coded on a scale of 0 to 185, with 185 indicating perfect health and 0 indicating very poor health.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· at baseline and 4 weeks after intervention start

Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy

GroupValue (Ratio)Spread
N-acetylcysteine 1800mg - Parkinson's Patient3.4220.7371
N-acetylcysteine 3600mg -Parkinson's Patient3.3340.8754
Placebo -Parkinson's Patient3.7451.418
N-acetylcysteine 1800mg - Healthy Volunteer4.2820.946
N-acetylcysteine 3600mg -Healthy Volunteer4.4150.928
Placebo -Healthy Volunteer3.9010.9698
Secondary and other outcome results(7)
Secondary outcomeMean· at baseline and 4 weeks after intervention start

Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported)

GroupValue (units on a scale)Spread
N-acetylcysteine 1800mg - Parkinson's Patient35.28615.152
N-acetylcysteine 3600mg -Parkinson's Patient31.50010.782
Placebo -Parkinson's Patient16.7144.923
N-acetylcysteine 1800mg - Healthy Volunteer1.0002.071
N-acetylcysteine 3600mg -Healthy Volunteer4.5002.082
Placebo -Healthy Volunteer3.1435.429
Secondary outcomeMean· at baseline and 4 weeks after intervention start

Mini Mental State Examination (MMSE)

GroupValue (units on a scale)Spread
N-acetylcysteine 1800mg - Parkinson's Patient29.5710.5345
N-acetylcysteine 3600mg -Parkinson's Patient29.8570.3780
Placebo -Parkinson's Patient29.5710.787
N-acetylcysteine 1800mg - Healthy Volunteer29.7780.667
N-acetylcysteine 3600mg -Healthy Volunteer29.6250.518
Placebo -Healthy Volunteer30.0000.000
Secondary outcomeMean· at baseline and 4 weeks after intervention start

Hamilton Depression Rating Scale (HAM-D)

GroupValue (units on a scale)Spread
N-acetylcysteine 1800mg - Parkinson's Patient3.7142.430
N-acetylcysteine 3600mg -Parkinson's Patient3.5712.430
Placebo -Parkinson's Patient1.8571.951
N-acetylcysteine 1800mg - Healthy Volunteer2.2223.032
N-acetylcysteine 3600mg -Healthy Volunteer1.8751.807
Placebo -Healthy Volunteer1.8892.2608
Secondary outcomeMean· at baseline and 4 weeks after intervention start

9-Hole Peg Board Test (9-HPT)

GroupValue (s (in seconds))Spread
N-acetylcysteine 1800mg - Parkinson's Patient37.02619.509
N-acetylcysteine 3600mg -Parkinson's Patient27.7955.660
Placebo -Parkinson's Patient28.6947.886
N-acetylcysteine 1800mg - Healthy Volunteer25.0884.489
N-acetylcysteine 3600mg -Healthy Volunteer24.5936.089
Placebo -Healthy Volunteer25.8344.964
Secondary outcomeMean· at baseline and 4 weeks after intervention start

10-Meter Walk Test

GroupValue (m/s (meters per second))Spread
N-acetylcysteine 1800mg - Parkinson's Patient7.8161.820
N-acetylcysteine 3600mg -Parkinson's Patient7.2891.281
Placebo -Parkinson's Patient6.8960.907
N-acetylcysteine 1800mg - Healthy Volunteer7.2530.713
N-acetylcysteine 3600mg -Healthy Volunteer10.4036.380
Placebo -Healthy Volunteer7.1410.929
Secondary outcomeMean· at baseline and 4 weeks after intervention start

Beck Anxiety Inventory

GroupValue (units on a scale)Spread
N-acetylcysteine 1800mg - Parkinson's Patient7.0006.782
N-acetylcysteine 3600mg -Parkinson's Patient9.0005.686
Placebo -Parkinson's Patient6.3335.046
N-acetylcysteine 1800mg - Healthy Volunteer3.7784.944
N-acetylcysteine 3600mg -Healthy Volunteer3.7505.365
Placebo -Healthy Volunteer2.6253.067
Secondary outcomeMean· at baseline and 4 weeks after intervention start

Parkinson's Disease Quality of Life Questionnaire (PDQLQ)

GroupValue (units on a scale)Spread
N-acetylcysteine 1800mg - Parkinson's Patient134.33334.488
N-acetylcysteine 3600mg -Parkinson's Patient142.28514.739
Placebo -Parkinson's Patient159.83313.586
N-acetylcysteine 1800mg - Healthy Volunteer175.66719.526
N-acetylcysteine 3600mg -Healthy Volunteer171.62518.647
Placebo -Healthy Volunteer175.25014.008

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
N-acetylcysteine 1800mg - Parkinson's PatientParkinson's patient N-acetylcysteine 1800mg/day for 30 days N-acetylcysteine: 900mg NAC effervescent tablets0 / 70 / 72 / 7
N-acetylcysteine 3600mg -Parkinson's PatientParkinson's patient N-acetylcysteine 3600mg daily for 30 days N-acetylcysteine: 900mg NAC effervescent tablets0 / 70 / 72 / 7
Placebo -Parkinson's PatientParkinson's patient Placebo effervescent tablets daily for 30 days Placebo: effervescent tablets0 / 70 / 72 / 7
N-acetylcysteine 1800mg - Healthy VolunteerHealthy Volunteer N-acetylcysteine 1800mg/day for 30 days N-acetylcysteine: 900mg NAC effervescent tablets0 / 90 / 92 / 9
N-acetylcysteine 3600mg -Healthy VolunteerHealthy Volunteer N-acetylcysteine 3600mg daily for 30 days N-acetylcysteine: 900mg NAC effervescent tablets0 / 80 / 82 / 8
Placebo -Healthy VolunteerHealthy Volunteer Placebo effervescent tablets daily for 30 days Placebo: effervescent tablets0 / 90 / 92 / 9

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 50 Years up to 75 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Diagnosis of idiopathic PD according to the United Kingdom Parkinson's Disease Society Brain Bank criteria (UKPDSBB) criteria (only for PD group * Age 50 to 75 years * Able to give informed consent for study participation * Not on any medication for PD (anticholinergic agents allowed) Exclusion Criteria: * Unable to give informed consent * Unable to undergo a brain MRI * PD duration ≥15 years * Receiving dopamine receptor blocking agents, including typical neuroleptics, prochlorperazine, and metoclopramide * Diagnosis of major depression or other axis I psychopathology * Modified Mini-Mental Status Exam (MMSE) ≤ 24/30 * Diagnosis of chronic or persistent illnesses that could affect oxidative stress status, such as diabetes or congestive heart failure * Significant concomitant medical disease limiting life expectancy to less than 12 months from study inclusion * Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease or ALS

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