Parkinson Disease
Conditions
Keywords
magnetic resonance spectroscopy, N-acetylcysteine, antioxidant, glutathione
Brief summary
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.
Detailed description
Parkinson's disease (PD) is a neurodegenerative disorder in which deficits of the primary intracellular antioxidant, glutathione (GSH), are postulated to mediate increased oxidative stress and mitochondrial dysfunction in the pathogenic cascade leading up to the loss of nigrostriatal dopaminergic neurons that is the hallmark of the disorder. Therefore, there is currently great interest in treatment strategies that can maintain, restore and/or elevate intracellular GSH levels. However, GSH does not readily cross the blood-brain barrier or the membranes of most cells, including neurons, so that direct dietary supplementation of the antioxidant has not proved viable in increasing its intracellular concentration. On the other hand, since the bioavailability of cysteine, which does cross both the blood-brain barrier and most cell membranes, is rate-limiting in the GSH synthesis pathway, this amino acid and its non-toxic derivatives, such as N-acetylcysteine (NAC), are being investigated as potential precursors that can be supplied through dietary means to spur in situ synthesis and elevation of brain GSH. The overall objective of this Exploratory/Developmental (R21) study is to use noninvasive proton magnetic resonance spectroscopy (1H MRS) to determine (a) whether levels of GSH are decreased in vivo in the brain of 30 patients with Parkinson's disease (PD) compared to matched controls, as has been found in postmortem brain; (b) whether GSH levels in PD brain increase significantly following 30 days of daily supplementation with 1800mg or 3600mg of NAC compared to baseline and placebo, 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. Additionally, 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
DRUGN-acetylcysteine
900mg NAC effervescent tablets
DRUGPlacebo
effervescent tablets
Sponsors
National Institute on Aging (NIA)
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | at baseline and 4 weeks after intervention start | 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
| Measure | Time frame | Description |
|---|---|---|
| Mini Mental State Examination (MMSE) | at baseline and 4 weeks after intervention start | 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. |
| Hamilton Depression Rating Scale (HAM-D) | at baseline and 4 weeks after intervention start | 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. |
| 9-Hole Peg Board Test (9-HPT) | at baseline and 4 weeks after intervention start | 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. |
| Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | at baseline and 4 weeks after intervention start | 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. |
| Beck Anxiety Inventory | at baseline and 4 weeks after intervention start | 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. |
| Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | at baseline and 4 weeks after intervention start | 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. |
| 10-Meter Walk Test | at baseline and 4 weeks after intervention start | 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. |
Countries
United States
Participant flow
Recruitment details
Enrollment for this pilot clinical study started in March 2012, as the end of the study in August 2016, 23 of 30 PD patients and 27 of 30 healthy volunteers (HV) subjects - a total 50- had participated in the study. All subjects enrolled at the Weill Cornell Parkinson's Disease and Movement Disorders Institute, led by the study neurologist.
Pre-assignment details
A total of 50 subjects enrolled into the study (23 PD patients and 27 HV subjects). Only 21 patients with PD and 26 HV subjects underwent the baseline assessments. Two PD patients and 1 HV subject were excluded from the study before assignment to groups. All exclusion were unrelated to the study protocol.
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient Parkinson's patient
N-acetylcysteine 1800mg/day for 30 days
N-acetylcysteine: 900mg NAC effervescent tablets | 7 |
| N-acetylcysteine 3600mg -Parkinson's Patient Parkinson's patient
N-acetylcysteine 3600mg daily for 30 days
N-acetylcysteine: 900mg NAC effervescent tablets | 7 |
| Placebo -Parkinson's Patient Parkinson's patient
Placebo effervescent tablets daily for 30 days
Placebo: effervescent tablets | 7 |
| N-acetylcysteine 1800mg - Healthy Volunteer Healthy Volunteer
N-acetylcysteine 1800mg/day for 30 days
N-acetylcysteine: 900mg NAC effervescent tablets | 9 |
| N-acetylcysteine 3600mg -Healthy Volunteer Healthy Volunteer
N-acetylcysteine 3600mg daily for 30 days
N-acetylcysteine: 900mg NAC effervescent tablets | 8 |
| Placebo -Healthy Volunteer Healthy Volunteer
Placebo effervescent tablets daily for 30 days
Placebo: effervescent tablets | 9 |
| Total | 47 |
Baseline characteristics
| Characteristic | N-acetylcysteine 1800mg - Parkinson's Patient | Total | Placebo -Healthy Volunteer | N-acetylcysteine 3600mg -Healthy Volunteer | N-acetylcysteine 1800mg - Healthy Volunteer | Placebo -Parkinson's Patient | N-acetylcysteine 3600mg -Parkinson's Patient |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.000 Years STANDARD_DEVIATION 5.259 | 60.809 Years STANDARD_DEVIATION 6.173 | 59.778 Years STANDARD_DEVIATION 5.995 | 56.625 Years STANDARD_DEVIATION 5.927 | 64.222 Years STANDARD_DEVIATION 7.807 | 62.429 Years STANDARD_DEVIATION 2.82 | 61.714 Years STANDARD_DEVIATION 6.264 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 7 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 40 Participants | 8 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 11 Participants | 4 Participants | 3 Participants | 4 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 33 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 7 Participants |
| Region of Enrollment United States | 7 participants | 47 participants | 9 participants | 8 participants | 9 participants | 7 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 37 Participants | 8 Participants | 7 Participants | 6 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 9 | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 2 / 7 | 2 / 7 | 2 / 7 | 2 / 9 | 2 / 8 | 2 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 9 | 0 / 8 | 0 / 9 |
Outcome results
Primary
Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The number of participants in the Participant Flow module is different from the Overall Number of Participants for brain GSH levels because of the total sample of 47 subjects enrolled in the study, baseline and post-treatment GSH values were available only for 43 subjects, whose data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 3.422 Ratio | Standard Deviation 0.7371 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 3.404 Ratio | Standard Deviation 0.7684 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 1.743 Ratio | Standard Deviation 0.4867 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 1.962 Ratio | Standard Deviation 0.5012 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 1.938 Ratio | Standard Deviation 0.3415 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 3.473 Ratio | Standard Deviation 1.01 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 3.334 Ratio | Standard Deviation 0.8754 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 2.108 Ratio | Standard Deviation 0.3788 |
| Placebo -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 2.118 Ratio | Standard Deviation 0.422 |
| Placebo -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 1.799 Ratio | Standard Deviation 0.4608 |
| Placebo -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 4.105 Ratio | Standard Deviation 1.292 |
| Placebo -Parkinson's Patient | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 3.745 Ratio | Standard Deviation 1.418 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 4.282 Ratio | Standard Deviation 0.946 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 2.161 Ratio | Standard Deviation 0.4027 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 4.843 Ratio | Standard Deviation 0.9884 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 2.190 Ratio | Standard Deviation 0.5077 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 2.007 Ratio | Standard Deviation 0.395 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 1.990 Ratio | Standard Deviation 0.3344 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 3.900 Ratio | Standard Deviation 0.724 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 4.415 Ratio | Standard Deviation 0.928 |
| Placebo -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Striatum) | 3.831 Ratio | Standard Deviation 0.8106 |
| Placebo -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Occipital) | 2.001 Ratio | Standard Deviation 0.4755 |
| Placebo -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | 4 weeks after intervention start ( In Occipital) | 2.298 Ratio | Standard Deviation 0.7663 |
| Placebo -Healthy Volunteer | Change of Cerebral Glutathione Levels as Measured by Proton Magnetic Resonance Spectroscopy | Baseline ( In Striatum) | 3.901 Ratio | Standard Deviation 0.9698 |
Secondary
10-Meter Walk Test
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The number of participants in the Participant Flow module is different from the Overall Number of Participants for 10-Meter Walk Test because of the total sample of 47 subjects enrolled in the study, baseline and post-treatment 10-Meter Walk Test score were available only for 46 subjects, whose data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | 10-Meter Walk Test | Baseline | 7.816 m/s (meters per second) | Standard Deviation 1.82 |
| N-acetylcysteine 1800mg - Parkinson's Patient | 10-Meter Walk Test | 4 weeks after intervention start | 10.513 m/s (meters per second) | Standard Deviation 7.136 |
| N-acetylcysteine 3600mg -Parkinson's Patient | 10-Meter Walk Test | Baseline | 7.289 m/s (meters per second) | Standard Deviation 1.281 |
| N-acetylcysteine 3600mg -Parkinson's Patient | 10-Meter Walk Test | 4 weeks after intervention start | 7.434 m/s (meters per second) | Standard Deviation 1.389 |
| Placebo -Parkinson's Patient | 10-Meter Walk Test | Baseline | 6.896 m/s (meters per second) | Standard Deviation 0.907 |
| Placebo -Parkinson's Patient | 10-Meter Walk Test | 4 weeks after intervention start | 6.296 m/s (meters per second) | Standard Deviation 0.929 |
| N-acetylcysteine 1800mg - Healthy Volunteer | 10-Meter Walk Test | Baseline | 7.253 m/s (meters per second) | Standard Deviation 0.713 |
| N-acetylcysteine 1800mg - Healthy Volunteer | 10-Meter Walk Test | 4 weeks after intervention start | 7.279 m/s (meters per second) | Standard Deviation 0.643 |
| N-acetylcysteine 3600mg -Healthy Volunteer | 10-Meter Walk Test | Baseline | 10.403 m/s (meters per second) | Standard Deviation 6.38 |
| N-acetylcysteine 3600mg -Healthy Volunteer | 10-Meter Walk Test | 4 weeks after intervention start | 9.740 m/s (meters per second) | Standard Deviation 5.958 |
| Placebo -Healthy Volunteer | 10-Meter Walk Test | Baseline | 7.141 m/s (meters per second) | Standard Deviation 0.929 |
| Placebo -Healthy Volunteer | 10-Meter Walk Test | 4 weeks after intervention start | 6.893 m/s (meters per second) | Standard Deviation 0.937 |
Secondary
9-Hole Peg Board Test (9-HPT)
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The measurement used for the 9-HPT is the average of time needed to complete the task with the dominant and non-dominant hand recorded in seconds. The presence of PD is expected to produce higher test times in seconds.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | Baseline | 37.026 s (in seconds) | Standard Deviation 19.509 |
| N-acetylcysteine 1800mg - Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 32.756 s (in seconds) | Standard Deviation 7.116 |
| N-acetylcysteine 3600mg -Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | Baseline | 27.795 s (in seconds) | Standard Deviation 5.66 |
| N-acetylcysteine 3600mg -Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 25.980 s (in seconds) | Standard Deviation 6.231 |
| Placebo -Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | Baseline | 28.694 s (in seconds) | Standard Deviation 7.886 |
| Placebo -Parkinson's Patient | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 28.084 s (in seconds) | Standard Deviation 9.373 |
| N-acetylcysteine 1800mg - Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | Baseline | 25.088 s (in seconds) | Standard Deviation 4.489 |
| N-acetylcysteine 1800mg - Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 24.940 s (in seconds) | Standard Deviation 2.995 |
| N-acetylcysteine 3600mg -Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | Baseline | 24.593 s (in seconds) | Standard Deviation 6.089 |
| N-acetylcysteine 3600mg -Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 22.511 s (in seconds) | Standard Deviation 6.325 |
| Placebo -Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | Baseline | 25.834 s (in seconds) | Standard Deviation 4.964 |
| Placebo -Healthy Volunteer | 9-Hole Peg Board Test (9-HPT) | 4 weeks after intervention start | 24.704 s (in seconds) | Standard Deviation 4.566 |
Secondary
Beck Anxiety Inventory
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The number of participants in the Participant Flow module is different from the Overall Number of Participants for Beck Anxiety Inventory (BAI) test because of the total sample of 47 subjects enrolled in the study, baseline and post-treatment BAI scores were available only for 45 subjects, whose data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Beck Anxiety Inventory | Baseline | 7.000 units on a scale | Standard Deviation 6.782 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Beck Anxiety Inventory | 4 weeks after intervention start | 3.000 units on a scale | Standard Deviation 2.45 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Beck Anxiety Inventory | Baseline | 9.000 units on a scale | Standard Deviation 5.686 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Beck Anxiety Inventory | 4 weeks after intervention start | 8.286 units on a scale | Standard Deviation 4.386 |
| Placebo -Parkinson's Patient | Beck Anxiety Inventory | Baseline | 6.333 units on a scale | Standard Deviation 5.046 |
| Placebo -Parkinson's Patient | Beck Anxiety Inventory | 4 weeks after intervention start | 5.714 units on a scale | Standard Deviation 5.438 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Beck Anxiety Inventory | Baseline | 3.778 units on a scale | Standard Deviation 4.944 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Beck Anxiety Inventory | 4 weeks after intervention start | 2.429 units on a scale | Standard Deviation 2.371 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Beck Anxiety Inventory | Baseline | 3.750 units on a scale | Standard Deviation 5.365 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Beck Anxiety Inventory | 4 weeks after intervention start | 5.714 units on a scale | Standard Deviation 5.345 |
| Placebo -Healthy Volunteer | Beck Anxiety Inventory | Baseline | 2.625 units on a scale | Standard Deviation 3.067 |
| Placebo -Healthy Volunteer | Beck Anxiety Inventory | 4 weeks after intervention start | 4.333 units on a scale | Standard Deviation 8.789 |
Secondary
Hamilton Depression Rating Scale (HAM-D)
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.
Time frame: at baseline and 4 weeks after intervention start
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | Baseline | 3.714 units on a scale | Standard Deviation 2.43 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 4.167 units on a scale | Standard Deviation 3.869 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | Baseline | 3.571 units on a scale | Standard Deviation 2.43 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 3.857 units on a scale | Standard Deviation 2.854 |
| Placebo -Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | Baseline | 1.857 units on a scale | Standard Deviation 1.951 |
| Placebo -Parkinson's Patient | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 1.714 units on a scale | Standard Deviation 1.976 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | Baseline | 2.222 units on a scale | Standard Deviation 3.032 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 1.286 units on a scale | Standard Deviation 1.89 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | Baseline | 1.875 units on a scale | Standard Deviation 1.807 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 0.714 units on a scale | Standard Deviation 1.113 |
| Placebo -Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | Baseline | 1.889 units on a scale | Standard Deviation 2.2608 |
| Placebo -Healthy Volunteer | Hamilton Depression Rating Scale (HAM-D) | 4 weeks after intervention start | 1.222 units on a scale | Standard Deviation 1.922 |
Secondary
Mini Mental State Examination (MMSE)
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.
Time frame: at baseline and 4 weeks after intervention start
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Mini Mental State Examination (MMSE) | Baseline | 29.571 units on a scale | Standard Deviation 0.5345 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 29.667 units on a scale | Standard Deviation 0.516 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Mini Mental State Examination (MMSE) | Baseline | 29.857 units on a scale | Standard Deviation 0.378 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 29.714 units on a scale | Standard Deviation 0.489 |
| Placebo -Parkinson's Patient | Mini Mental State Examination (MMSE) | Baseline | 29.571 units on a scale | Standard Deviation 0.787 |
| Placebo -Parkinson's Patient | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 30.000 units on a scale | Standard Deviation 0 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 29.857 units on a scale | Standard Deviation 0.378 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Mini Mental State Examination (MMSE) | Baseline | 29.778 units on a scale | Standard Deviation 0.667 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Mini Mental State Examination (MMSE) | Baseline | 29.625 units on a scale | Standard Deviation 0.518 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 30.000 units on a scale | Standard Deviation 0 |
| Placebo -Healthy Volunteer | Mini Mental State Examination (MMSE) | Baseline | 30.000 units on a scale | Standard Deviation 0 |
| Placebo -Healthy Volunteer | Mini Mental State Examination (MMSE) | 4 weeks after intervention start | 29.750 units on a scale | Standard Deviation 0.463 |
Secondary
Parkinson's Disease Quality of Life Questionnaire (PDQLQ)
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The number of participants in the Participant Flow module is different from the Overall Number of Participants for PDQLQ because of the total sample of 47 subjects enrolled in the study, baseline and post-treatment PDQLQ scores were available only for 43 subjects, whose data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 134.333 units on a scale | Standard Deviation 34.488 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 127.100 units on a scale | Standard Deviation 45.081 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 142.285 units on a scale | Standard Deviation 14.739 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 135.571 units on a scale | Standard Deviation 14.01 |
| Placebo -Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 159.833 units on a scale | Standard Deviation 13.586 |
| Placebo -Parkinson's Patient | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 159.429 units on a scale | Standard Deviation 17.634 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 175.667 units on a scale | Standard Deviation 19.526 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 177.833 units on a scale | Standard Deviation 11.565 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 171.625 units on a scale | Standard Deviation 18.647 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 165.142 units on a scale | Standard Deviation 17.601 |
| Placebo -Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | Baseline | 175.250 units on a scale | Standard Deviation 14.008 |
| Placebo -Healthy Volunteer | Parkinson's Disease Quality of Life Questionnaire (PDQLQ) | 4 weeks after intervention start | 181.750 units on a scale | Standard Deviation 2.964 |
Secondary
Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported)
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.
Time frame: at baseline and 4 weeks after intervention start
Population: The number of participants in the Participant Flow module is different from the Overall Number of Participants for Unified Parkinson's Disease Rating Scale (UPDRS) because of the total sample of 47 subjects enrolled in the study, baseline and post-treatment UPDRS were available only for 40 subjects, whose data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine 1800mg - Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 35.286 units on a scale | Standard Deviation 15.152 |
| N-acetylcysteine 1800mg - Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 23.857 units on a scale | Standard Deviation 16.547 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 31.500 units on a scale | Standard Deviation 10.782 |
| N-acetylcysteine 3600mg -Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 24.249 units on a scale | Standard Deviation 16.547 |
| Placebo -Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 16.714 units on a scale | Standard Deviation 4.923 |
| Placebo -Parkinson's Patient | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 13.857 units on a scale | Standard Deviation 6.817 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 1.000 units on a scale | Standard Deviation 2.071 |
| N-acetylcysteine 1800mg - Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 0.600 units on a scale | Standard Deviation 1.342 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 4.500 units on a scale | Standard Deviation 2.082 |
| N-acetylcysteine 3600mg -Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 3.000 units on a scale | Standard Deviation 2.16 |
| Placebo -Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | Baseline | 3.143 units on a scale | Standard Deviation 5.429 |
| Placebo -Healthy Volunteer | Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-V (Total Score Reported) | 4 weeks after intervention start | 1.857 units on a scale | Standard Deviation 3.185 |