Parkinson Disease
Conditions
Keywords
Parkinson disease, PD, Coenzyme Q10, CoQ
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of high dosages of Coenzyme Q10 in slowing clinical decline in people who have early Parkinson disease.
Detailed description
Parkinson disease (PD) is a progressive neurodegenerative disease that affects more than 1,000,000 Americans. Currently there is no proven therapy to reduce the rate of progression of PD. In a previous phase II clinical trial, investigators demonstrated that Coenzyme Q10 (CoQ) at dosages of 300, 600, and 1200 mg/day was safe and well-tolerated in individuals with early, untreated PD. The findings also suggested that CoQ may slow the progressive impairment of PD as measured by the Unified Parkinson Disease Rating Scale (UPDRS). In this study, researchers will conduct a randomized, placebo-controlled, phase III trial of CoQ to confirm and extend the results of the earlier phase II study. The primary objective of this trial is to compare the effect of two dosages of CoQ (1200 and 2400 mg/day) and placebo on the total UPDRS score in people with early PD. The study also will evaluate independent function, cognition, and quality of life. Plasma CoQ levels will be measured at months 1, 8 and 16 and correlated with changes in UPDRS scores. Participants will be randomly assigned to receive a placebo (an inactive substance), 1200 mg/d CoQ, or 2400 mg/d CoQ. They will be evaluated at screening, baseline, and during visits at months 1, 4, 8, 12, and 16. Information gained from this trial could lead to changes in management of people with early PD.
Interventions
DRUGCoenzyme Q10 with vitamin E
2400 mg dose - eight 300 mg Coenzyme Q10 chewable wafers taken orally four times a day; 1200 mg dose - four 300 mg Coenzyme Q10 and four placebo chewable wafers taken orally four times a day.
DRUGplacebo with vitamin E
placebo or an inactive substance (with vitamin E 1200 IU/day); Placebo - eight chewable wafers taken orally four times a day.
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Rochester
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
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of all 3 of the cardinal features of Parkinson disease (resting tremor, bradykinesia and rigidity). The clinical signs must be asymmetric. * The diagnosis of Parkinson disease within 5 years prior to the Screening Visit. * Age 30 or older. * Female subjects must not be of childbearing potential or must use an approved form of contraception for the duration of the trial.
Exclusion criteria
* Use of any Parkinson disease medication within 60 days prior to the Baseline Visit. * Duration of previous use of symptomatic medication for Parkinson disease cannot exceed 90 days such as levodopa, dopaminergic agonists (including ropinirole, pramipexole, pergolide, cabergoline, and the rotigotine transdermal system), selegiline, rasagiline, amantadine, and anticholinergic agents. * Parkinsonism due to drugs including neuroleptics, alphamethyldopa, reserpine, metoclopramide, valproic acid. * Use of antioxidants (such as selegiline, rasagiline, vitamins E and C), additional supplemental vitamins or minerals, regular use of neuroleptics, chloramphenicol, valproic acid, warfarin. * Other parkinsonian disorders. * Modified Hoehn and Yahr score of 3 or greater at Screening Visit or Baseline Visit. * UPDRS tremor score of 3 or greater at Screening Visit or Baseline Visit. * Mini-Mental State Examination (MMSE) score of 25 or less. * History of stroke. * Disability sufficient to require treatment with dopaminergic medication or anticipated need for dopaminergic medication within next 3 months. * Other serious illness, including psychiatric illness. * Patients with active cardiovascular, peripheral vascular or cerebrovascular disease within the past year. * Clinically serious abnormalities in the Screening Visit laboratory studies or electrocardiogram. * Use of methylphenidate, cinnarizine, reserpine, amphetamine or a MAO-A inhibitor within 6 months prior to the Baseline Visit. * Unstable dose of CNS active therapies. * Use of appetite suppressants within 60 days prior to the Baseline Visit. * History of active epilepsy within the last 5 years. * Revised Hamilton Rating Scale for Depression of 11 or greater. * Participation in other drug studies or use of other investigational drugs within 30 days prior to Screening Visit. * History of electroconvulsive therapy. * History of any brain surgery for Parkinson disease. * History of structural brain disease such as prior trauma causing damage detected on a CT scan or MRI, hydrocephalus, or prior brain neoplasms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176)) | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline visit and month 16 or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first. The UPDRS score has three components, each consisting of questions answered on a 0-4 point scale. Part I assesses mentation, behavior and mood; Part II assesses activities of daily living in the week prior to the designated visit; and Part III assesses motor abilities at the time of the visit. A total of 31 items are included in Parts I, II and III. Each item will receive a score ranging from 0 to 4 where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total score ranges from 0-176. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Modified Rankin Scale From Baseline to 16 Months | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | The Modified Rankin Scale is a global functional health index with a strong accent on physical disability. Subjects are scored on a scale of 0 (no symptoms at all) to 5 (severe disability: bedridden incontinent, and requiring constant nursing care and attention. |
| Change in PD Quality of Life Scale From Baseline to 16 Months | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | The subject will complete a questionnaire that will evaluate how Parkinson disease has affected their health and overall quality of life at each visit. The total quality of life scale measures a total of 33 aspects of quality of life. Each aspect is rated on scale of 0 (best outcome) to 4 (worst outcome). Total score range is 0-132. A higher score or increased score compared to a previous visit indicates a lowered quality of life. |
| Change in Symbol Digit Modalities Test From Baseline to 16 Months | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | The Symbol Digit Modalities Test screens cognitive impairment by using a simple substitution tasks that individuals with normal functioning can easily perform. The test score range is from 0(worst outcome) to 110 (best outcome). |
| Change in Hoehn & Yahr Score From Baseline to 16 Months | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | The Modified Hoehn and Yahr Scale is an 8-level Parkinson disease staging instrument. The investigator will assess disease stage at each level. The disease stages range from the best outcome of 0 (no signs of disease) to the worst outcome of 5 (wheelchair bound or bedridden unless aided). |
| CoQ10 Levels in Plasma | Baseline, 1, 8 and 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | Based on samples analyzed to date |
| Adverse Experiences: Back Pain | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with back pain |
| Adverse Experiences: Constipation | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with constipation |
| Adverse Experiences: Insomnia | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with insomnia |
| Adverse Experiences: Anxiety | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with anxiety |
| Adverse Experiences: Tremor | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with tremor |
| Change in Modified Schwab & England Independence Scale From Baseline to 16 Months | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | This scale measures activities of daily living. This is an investigator and subject assessment of the subject's level of independence at all scheduled visits. The subject is scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to pre-Parkinson disease ability. Scores range in increments of 10%: 100% for normal (subject is completely independent; essentially normal) to 0% (vegetative functions such as swallowing, bladder and bowel functions are not functioning; bedridden). |
| Adverse Experiences: Diarrhoea | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with diarrhoea |
| Adverse Experiences: Headache | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with headache |
| Adverse Experiences: Urinary Tract Infection | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of patients with urinary tract infections |
| Adverse Experiences: Nausea | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with nausea |
| Adverse Experiences: Hypertension | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with hypertension |
| Adverse Experiences: Depression | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with depression |
| Adverse Experiences: Constipation: Moderate/Severe | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with moderate/severe constipation |
| Adverse Experiences: Anxiety: Moderate/Severe | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with moderate/severe anxiety |
| Adverse Experiences: Back Pain: Moderate/Severe | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with moderate/severe back pain |
| Adverse Experiences: Insomnia: Moderate/Severe | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with moderate/severe insomnia |
| Adverse Experiences: Nasopharyngitis | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | Number of participants with nasopharyngitis |
Countries
Canada, United States
Participant flow
Recruitment details
The recruitment period for the required 600 patients was from January 2009 to October 2010. There were 67 sites (60 in the US and 7 in Canada) that participated in the study. Most of these sites were located at or affiliated with large academic medical centers.
Pre-assignment details
Patients were required to undergo a thorough screening visit. If patients were taking CoEnzyme Q10 but otherwise eligible for assignment, they were asked to return after a wash out period of 60 to 120 days based on daily dosage.
Participants by arm
| Arm | Count |
|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day Randomized to active treatment (Coenzyme Q10 2400 mg/day with vitamin E 1200 IU/day) | 196 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day) | 201 |
| C. Placebo With Vitamin E 1200 IU/Day Placebo (with vitamin E 1200 IU/day) | 203 |
| Total | 600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 17 | 19 | 29 |
Baseline characteristics
| Characteristic | A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | C. Placebo With Vitamin E 1200 IU/Day | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 83 Participants | 88 Participants | 70 Participants | 241 Participants |
| Age, Categorical Between 18 and 65 years | 113 Participants | 113 Participants | 133 Participants | 359 Participants |
| Age Continuous | 62.8 years STANDARD_DEVIATION 9.66 | 63.3 years STANDARD_DEVIATION 9.83 | 61.3 years STANDARD_DEVIATION 10.5 | 62.5 years STANDARD_DEVIATION 10.03 |
| Region of Enrollment Canada | 31 participants | 30 participants | 29 participants | 90 participants |
| Region of Enrollment United States | 165 participants | 171 participants | 174 participants | 510 participants |
| Sex: Female, Male Female | 68 Participants | 62 Participants | 73 Participants | 203 Participants |
| Sex: Female, Male Male | 128 Participants | 139 Participants | 130 Participants | 397 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 106 / 196 | 113 / 201 | 108 / 203 |
| serious Total, serious adverse events | 7 / 196 | 13 / 201 | 13 / 203 |
Outcome results
Primary
Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176))
Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline visit and month 16 or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first. The UPDRS score has three components, each consisting of questions answered on a 0-4 point scale. Part I assesses mentation, behavior and mood; Part II assesses activities of daily living in the week prior to the designated visit; and Part III assesses motor abilities at the time of the visit. A total of 31 items are included in Parts I, II and III. Each item will receive a score ranging from 0 to 4 where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total score ranges from 0-176.
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: Eligible research participants were assigned by randomization to one of three treatment groups: CoQ10 2400 mg/day, CoQ10 1200 mg/day or matching placebo. All participants also received 1200 IU of vitamin E daily.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176)) | 8.01 units on a scale | Standard Error 0.63 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176)) | 7.50 units on a scale | Standard Error 0.62 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176)) | 6.92 units on a scale | Standard Error 0.63 |
Comparison: ANCOVA is used with the change in total UPDRS of Coenzyme Q10 1200 mg/day arm compared to placebo group.p-value: >0.02597.5% CI: [-1.33, 2.51]ANCOVA
Comparison: ANCOVA is used with the change in total UPDRS of Coenzyme Q10 2400 mg/day arm compared to placebo group.p-value: >0.02595% CI: [-0.85, 3.03]ANCOVA
Secondary
Adverse Experiences: Anxiety
Number of participants with anxiety
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety | 12 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety | 13 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety | 14 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.46, 1.79]ANCOVA
Secondary
Adverse Experiences: Anxiety: Moderate/Severe
Number of participants with moderate/severe anxiety
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety: Moderate/Severe | 9 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety: Moderate/Severe | 9 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Anxiety: Moderate/Severe | 7 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.55, 3.24]Fisher Exact
Secondary
Adverse Experiences: Back Pain
Number of participants with back pain
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain | 9 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain | 13 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain | 9 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.57, 2.8]Fisher Exact
Secondary
Adverse Experiences: Back Pain: Moderate/Severe
Number of participants with moderate/severe back pain
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain: Moderate/Severe | 7 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain: Moderate/Severe | 9 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Back Pain: Moderate/Severe | 7 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.48, 9999.99]Fisher Exact
Secondary
Adverse Experiences: Constipation
Number of participants with constipation
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation | 7 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation | 13 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation | 7 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subject experiencing a particular adverse experiencep-value: <0.0595% CI: [0.62, 3.57]Fisher Exact
Secondary
Adverse Experiences: Constipation: Moderate/Severe
Number of participants with moderate/severe constipation
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation: Moderate/Severe | 3 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation: Moderate/Severe | 10 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Constipation: Moderate/Severe | 3 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.64, 8.01]Fisher Exact
Secondary
Adverse Experiences: Depression
Number of participants with depression
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Depression | 9 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Depression | 6 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Depression | 14 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.25, 1.12]Fisher Exact
Secondary
Adverse Experiences: Diarrhoea
Number of participants with diarrhoea
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Diarrhoea | 6 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Diarrhoea | 9 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Diarrhoea | 11 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.31, 1.52]Fisher Exact
Secondary
Adverse Experiences: Headache
Number of participants with headache
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Headache | 9 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Headache | 8 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Headache | 11 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.36, 1.7]Fisher Exact
Secondary
Adverse Experiences: Hypertension
Number of participants with hypertension
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Hypertension | 5 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Hypertension | 7 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Hypertension | 0 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [2.77, 9999.99]Fisher Exact
Secondary
Adverse Experiences: Insomnia
Number of participants with insomnia
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia | 6 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia | 13 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia | 6 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.65, 4.2]Fisher Exact
Secondary
Adverse Experiences: Insomnia: Moderate/Severe
Number of participants with moderate/severe insomnia
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia: Moderate/Severe | 2 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia: Moderate/Severe | 9 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Insomnia: Moderate/Severe | 0 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [2.51, 9999.99]Fisher Exact
Secondary
Adverse Experiences: Nasopharyngitis
Number of participants with nasopharyngitis
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Nasopharyngitis | 7 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Nasopharyngitis | 9 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Nasopharyngitis | 3 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.81, 9.72]Fisher Exact
Secondary
Adverse Experiences: Nausea
Number of participants with nausea
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Nausea | 7 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Nausea | 7 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Nausea | 10 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.31, 1.62]Fisher Exact
Secondary
Adverse Experiences: Tremor
Number of participants with tremor
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Tremor | 10 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Tremor | 13 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Tremor | 8 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.66, 3.41]Fisher Exact
Secondary
Adverse Experiences: Urinary Tract Infection
Number of patients with urinary tract infections
Time frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)
Population: All participants were used in primary and secondary outcome analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Urinary Tract Infection | 6 participants |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Adverse Experiences: Urinary Tract Infection | 8 participants |
| C. Placebo With Vitamin E 1200 IU/Day | Adverse Experiences: Urinary Tract Infection | 3 participants |
Comparison: All adverse experiences were tabulated by treatment group, severity and perceived relationship to study medication. Fisher's exact test was used to compare active treatment arms to the placebo arm with regard to the proportion of subjects experiencing a particular adverse experience.p-value: <0.0595% CI: [0.69, 8.58]Fisher Exact
Secondary
Change in Hoehn & Yahr Score From Baseline to 16 Months
The Modified Hoehn and Yahr Scale is an 8-level Parkinson disease staging instrument. The investigator will assess disease stage at each level. The disease stages range from the best outcome of 0 (no signs of disease) to the worst outcome of 5 (wheelchair bound or bedridden unless aided).
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants were used in primary and secondary outcome analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in Hoehn & Yahr Score From Baseline to 16 Months | .21 units on a scale | Standard Error 0.03 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in Hoehn & Yahr Score From Baseline to 16 Months | .20 units on a scale | Standard Error 0.03 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in Hoehn & Yahr Score From Baseline to 16 Months | .16 units on a scale | Standard Error 0.03 |
Comparison: Change from Baseline Visit to 16-month visit on Hoehn \& Yahr Score will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.344597.5% CI: [-0.04, 0.13]ANCOVA
Comparison: Change from Baseline visit to 16-month visit on Hoehn \& Yahr will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.23995% CI: [-0.04, 0.14]ANCOVA
Secondary
Change in Modified Rankin Scale From Baseline to 16 Months
The Modified Rankin Scale is a global functional health index with a strong accent on physical disability. Subjects are scored on a scale of 0 (no symptoms at all) to 5 (severe disability: bedridden incontinent, and requiring constant nursing care and attention.
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants were used in primary and secondary outcome analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in Modified Rankin Scale From Baseline to 16 Months | .38 units on a scale | Standard Error 0.05 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in Modified Rankin Scale From Baseline to 16 Months | .31 units on a scale | Standard Error 0.05 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in Modified Rankin Scale From Baseline to 16 Months | .40 units on a scale | Standard Error 0.05 |
Comparison: Change from Baseline Visit to 16-month visit on Modified Rankin Scale will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: <0.161597.5% CI: [-0.25, 0.06]ANCOVA
Comparison: Change from Baseline Visit to 16-month visit on Modified Rankin will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.762795% CI: [-0.17, 0.13]ANCOVA
Secondary
Change in Modified Schwab & England Independence Scale From Baseline to 16 Months
This scale measures activities of daily living. This is an investigator and subject assessment of the subject's level of independence at all scheduled visits. The subject is scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to pre-Parkinson disease ability. Scores range in increments of 10%: 100% for normal (subject is completely independent; essentially normal) to 0% (vegetative functions such as swallowing, bladder and bowel functions are not functioning; bedridden).
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants were used in primary and secondary outcome analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in Modified Schwab & England Independence Scale From Baseline to 16 Months | -4.94 units on a scale | Standard Error 0.62 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in Modified Schwab & England Independence Scale From Baseline to 16 Months | -4.29 units on a scale | Standard Error 0.62 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in Modified Schwab & England Independence Scale From Baseline to 16 Months | -4.07 units on a scale | Standard Error 0.62 |
Comparison: Change from Baseline Visit to 16-month visit on Modified Schwab \& England will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.794397.5% CI: [-2.12, 1.68]ANCOVA
Comparison: Change from Baseline Visit to 16-month on Modified Schwab \& England will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.30695% CI: [-2.79, 1.04]ANCOVA
Secondary
Change in PD Quality of Life Scale From Baseline to 16 Months
The subject will complete a questionnaire that will evaluate how Parkinson disease has affected their health and overall quality of life at each visit. The total quality of life scale measures a total of 33 aspects of quality of life. Each aspect is rated on scale of 0 (best outcome) to 4 (worst outcome). Total score range is 0-132. A higher score or increased score compared to a previous visit indicates a lowered quality of life.
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants were used in primary and secondary outcome analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in PD Quality of Life Scale From Baseline to 16 Months | 5.06 units on a scale | Standard Error 0.89 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in PD Quality of Life Scale From Baseline to 16 Months | 6.12 units on a scale | Standard Error 0.87 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in PD Quality of Life Scale From Baseline to 16 Months | 5.57 units on a scale | Standard Error 0.89 |
Comparison: Change from Baseline Visit to 16-month visit on PD Quality of Life Scale will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.638397.5% CI: [-2.1, 3.21]ANCOVA
Comparison: Change from Baseline Visit to 16-month visit on PD Quality of Life Scale will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.66795% CI: [-3.2, 2.17]ANCOVA
Secondary
Change in Symbol Digit Modalities Test From Baseline to 16 Months
The Symbol Digit Modalities Test screens cognitive impairment by using a simple substitution tasks that individuals with normal functioning can easily perform. The test score range is from 0(worst outcome) to 110 (best outcome).
Time frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants were used in primary and secondary outcome analyses.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | Change in Symbol Digit Modalities Test From Baseline to 16 Months | -3.36 units on a scale | Standard Error 1.4 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | Change in Symbol Digit Modalities Test From Baseline to 16 Months | -0.49 units on a scale | Standard Error 1.39 |
| C. Placebo With Vitamin E 1200 IU/Day | Change in Symbol Digit Modalities Test From Baseline to 16 Months | -3.02 units on a scale | Standard Error 1.48 |
Comparison: Change from Baseline Visit to 16-month visit on Symbol Digit Modalities Test will be analyzed using ANCOVA in the same way as for the primary outcome variable.p-value: 0.67197.5% CI: [-2.09, 3.06]ANCOVA
Comparison: Change from Baseline Visit to 16-month visit on Symbol Digit Modalities Test will be analyzed using ANCOVA in the same way as for the primary outcome variablep-value: 0.67195% CI: [-3.34, 1.87]ANCOVA
Secondary
CoQ10 Levels in Plasma
Based on samples analyzed to date
Time frame: Baseline, 1, 8 and 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
Population: All participants have been included and data is based on samples analyzed to date.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 8 month visit | 3.32 ug/ml | Standard Deviation 1.93 |
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 1 month visit | 3.55 ug/ml | Standard Deviation 1.83 |
| A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 16 month visit | 2.88 ug/ml | Standard Deviation 2.02 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 8 month visit | 2.67 ug/ml | Standard Deviation 1.33 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 1 month visit | 2.57 ug/ml | Standard Deviation 1.29 |
| B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 16 month visit | 2.17 ug/ml | Standard Deviation 1.18 |
| C. Placebo With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 1 month visit | .75 ug/ml | Standard Deviation 0.36 |
| C. Placebo With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 16 month visit | .63 ug/ml | Standard Deviation 0.27 |
| C. Placebo With Vitamin E 1200 IU/Day | CoQ10 Levels in Plasma | 8 month visit | 1.07 ug/ml | Standard Deviation 0.83 |
Comparison: The analysis will be using the actual change of plasma levels of CoQ10(from final visit to baseline) as predictors of UPDRS worsening. Correlation of UPDRS worsening with plasma levels of CoQ10 will be calculated for all treatment groups.p-value: 0.057795% CI: [-0.018, 1.091]ANOVA
Comparison: The analysis will be using the actual change of plasma levels of CoQ10(from final to baseline) as predictors of UPDRS worsening. Correlation of UPDRS worsening with plasma levels of CoQ10 will be calculated for the treatment group of Coenzyme Q10 2400 mg/day.p-value: 0.588995% CI: [-0.647, 1.136]ANOVA
Comparison: The analysis will be using the actual change of plasma levels of CoQ10(from final to baseline) as predictors of UPDRS worsening. Correlation of UPDRS worsening with plasma levels of CoQ10 will be calculated for the treatment group of Coenzyme Q10 1200 mg/day.p-value: 0.300695% CI: [-0.569, 1.831]ANOVA
Comparison: The analysis will be using the actual change of plasma levels of CoQ10(from final to baseline) as predictors of UPDRS worsening. Correlation of UPDRS worsening with plasma levels of CoQ10 will be calculated for the placebo group.p-value: 0.09695% CI: [-0.382, 4.633]ANOVA