Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (QE3)

This study has been terminated.
(The investigational drug is unlikely to demonstrate efficacy over placebo for this indication. However, no safety issues were discovered.)
Sponsor:
Collaborators:
University of Rochester
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00740714
First received: August 22, 2008
Last updated: December 24, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Drug: Coenzyme Q10 with vitamin E
Drug: placebo with vitamin E
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Coenzyme Q10 in Parkinson Disease - Phase III

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176)) [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change in Modified Schwab & England Independence Scale From Baseline to 16 Months [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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).

  • Change in Modified Rankin Scale From Baseline to 16 Months [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1, 8 and 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first ] [ Designated as safety issue: Yes ]
    Based on samples analyzed to date

  • Adverse Experiences: Back Pain [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with back pain

  • Adverse Experiences: Constipation [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with constipation

  • Adverse Experiences: Insomnia [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with insomnia

  • Adverse Experiences: Anxiety [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with anxiety

  • Adverse Experiences: Tremor [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with tremor

  • Adverse Experiences: Nasopharyngitis [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with nasopharyngitis

  • Adverse Experiences: Diarrhoea [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with diarrhoea

  • Adverse Experiences: Headache [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with headache

  • Adverse Experiences: Urinary Tract Infection [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of patients with urinary tract infections

  • Adverse Experiences: Nausea [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with nausea

  • Adverse Experiences: Hypertension [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with hypertension

  • Adverse Experiences: Depression [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with depression

  • Adverse Experiences: Constipation: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with moderate/severe constipation

  • Adverse Experiences: Anxiety: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with moderate/severe anxiety

  • Adverse Experiences: Back Pain: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with moderate/severe back pain

  • Adverse Experiences: Insomnia: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ] [ Designated as safety issue: Yes ]
    Number of participants with moderate/severe insomnia


Enrollment: 600
Study Start Date: December 2008
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Randomized to active treatment (Coenzyme Q10 2400 mg/day with vitamin E 1200 IU/day)
Drug: Coenzyme 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.
Other Name: Coenzyme Q10, ubiquinone, ubidecarenone
Experimental: B
Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)
Drug: Coenzyme 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.
Other Name: Coenzyme Q10, ubiquinone, ubidecarenone
Placebo Comparator: C
Placebo (with vitamin E 1200 IU/day)
Drug: placebo with vitamin E
placebo or an inactive substance (with vitamin E 1200 IU/day); Placebo - eight chewable wafers taken orally four times a day.

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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00740714

  Show 68 Study Locations
Sponsors and Collaborators
Weill Medical College of Cornell University
University of Rochester
Investigators
Principal Investigator: M. Flint Beal, MD Weill Medical College of Cornell University, New York Hospital Department of Neurology
Principal Investigator: David Oakes, PhD University of Rochester, Department of Biostatistics
Principal Investigator: Ira Shoulson, MD University of Rochester, Clinical Trials Coordination Center
  More Information

Publications:
Shoulson, I, et al. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson disease: A randomized, placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Annals of Neurology, 2002; 51:124-35.
Shults CW. CoQ in neurodegenerative diseases. Curr Med Chem 2003; 10(19):1917-21.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Parkinson Study Group QE3 Investigators, Beal MF, Oakes D, Shoulson I, Henchcliffe C, Galpern WR, Haas R, Juncos JL, Nutt JG, Voss TS, Ravina B, Shults CM, Helles K, Snively V, Lew MF, Griebner B, Watts A, Gao S, Pourcher E, Bond L, Kompoliti K, Agarwal P, Sia C, Jog M, Cole L, Sultana M, Kurlan R, Richard I, Deeley C, Waters CH, Figueroa A, Arkun A, Brodsky M, Ondo WG, Hunter CB, Jimenez-Shahed J, Palao A, Miyasaki JM, So J, Tetrud J, Reys L, Smith K, Singer C, Blenke A, Russell DS, Cotto C, Friedman JH, Lannon M, Zhang L, Drasby E, Kumar R, Subramanian T, Ford DS, Grimes DA, Cote D, Conway J, Siderowf AD, Evatt ML, Sommerfeld B, Lieberman AN, Okun MS, Rodriguez RL, Merritt S, Swartz CL, Martin WR, King P, Stover N, Guthrie S, Watts RL, Ahmed A, Fernandez HH, Winters A, Mari Z, Dawson TM, Dunlop B, Feigin AS, Shannon B, Nirenberg MJ, Ogg M, Ellias SA, Thomas CA, Frei K, Bodis-Wollner I, Glazman S, Mayer T, Hauser RA, Pahwa R, Langhammer A, Ranawaya R, Derwent L, Sethi KD, Farrow B, Prakash R, Litvan I, Robinson A, Sahay A, Gartner M, Hinson VK, Markind S, Pelikan M, Perlmutter JS, Hartlein J, Molho E, Evans S, Adler CH, Duffy A, Lind M, Elmer L, Davis K, Spears J, Wilson S, Leehey MA, Hermanowicz N, Niswonger S, Shill HA, Obradov S, Rajput A, Cowper M, Lessig S, Song D, Fontaine D, Zadikoff C, Williams K, Blindauer KA, Bergholte J, Propsom CS, Stacy MA, Field J, Mihaila D, Chilton M, Uc EY, Sieren J, Simon DK, Kraics L, Silver A, Boyd JT, Hamill RW, Ingvoldstad C, Young J, Thomas K, Kostyk SK, Wojcieszek J, Pfeiffer RF, Panisset M, Beland M, Reich SG, Cines M, Zappala N, Rivest J, Zweig R, Lumina LP, Hilliard CL, Grill S, Kellermann M, Tuite P, Rolandelli S, Kang UJ, Young J, Rao J, Cook MM, Severt L, Boyar K. A randomized clinical trial of high-dosage coenzyme q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol. 2014 May;71(5):543-52. doi: 10.1001/jamaneurol.2014.131.

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00740714     History of Changes
Other Study ID Numbers: U01NS050324, U01NS050573
Study First Received: August 22, 2008
Results First Received: July 24, 2012
Last Updated: December 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Parkinson disease
PD
Coenzyme Q10
CoQ

Additional relevant MeSH terms:
Coenzyme Q10
Ubiquinone
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on August 01, 2014