Effects of Coenzyme Q10 (CoQ) in Parkinson Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Coenzyme Q10 in Parkinson Disease - Phase III

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Coenzyme Q10 with vitamin E
* Drug: placebo with vitamin E


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Randomized to active treatment (Coenzyme Q10 2400 mg/day with vitamin E 1200 IU/day) | Drug: Coenzyme Q10 with vitamin E<br>* 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.<br>* Other names: Coenzyme Q10, ubiquinone, ubidecarenone;|
| Experimental: B<br>Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day) | Drug: Coenzyme Q10 with vitamin E<br>* 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.<br>* Other names: Coenzyme Q10, ubiquinone, ubidecarenone;|
| Placebo Comparator: C<br>Placebo (with vitamin E 1200 IU/day) | Drug: placebo with vitamin E<br>* placebo or an inactive substance (with vitamin E 1200 IU/day); Placebo - eight chewable wafers taken orally four times a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| 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. | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| 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. | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| 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). | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| 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). | Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| CoQ10 Levels in Plasma | Based on samples analyzed to date | Baseline, 1, 8 and 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first | 
| Adverse Experiences: Back Pain | Number of participants with back pain | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Constipation | Number of participants with constipation | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Insomnia | Number of participants with insomnia | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Anxiety | Number of participants with anxiety | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Tremor | Number of participants with tremor | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Nasopharyngitis | Number of participants with nasopharyngitis | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Diarrhoea | Number of participants with diarrhoea | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Headache | Number of participants with headache | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Urinary Tract Infection | Number of patients with urinary tract infections | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Nausea | Number of participants with nausea | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Hypertension | Number of participants with hypertension | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Depression | Number of participants with depression | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Constipation: Moderate/Severe | Number of participants with moderate/severe constipation | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Anxiety: Moderate/Severe | Number of participants with moderate/severe anxiety | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Back Pain: Moderate/Severe | Number of participants with moderate/severe back pain | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 
| Adverse Experiences: Insomnia: Moderate/Severe | Number of participants with moderate/severe insomnia | Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson disease, PD, Coenzyme Q10, CoQ