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:

National Institute of Neurological Disorders and Stroke (NINDS)

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

History of Changes

Results First Received: July 24, 2012

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
Condition:	Parkinson Disease
Interventions:	Drug: Coenzyme Q10 with vitamin E Drug: placebo with vitamin E

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

	Description
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)
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)
C. Placebo With Vitamin E 1200 IU/Day	Placebo (with vitamin E 1200 IU/day)

Participant Flow: Overall Study

	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
STARTED	196 ^[1]	201 ^[1]	203 ^[1]
Reaching Endpoint Before May 6, 2011	86	87	94
Active Patients at Study Termination	24	12	33
COMPLETED	179	182	174
NOT COMPLETED	17	19	29
Withdrawal by Subject	17	19	29

[1]	Randomized throughout the recruitment period

Baseline Characteristics

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Reporting Groups

	Description
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)
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)
C. Placebo With Vitamin E 1200 IU/Day	Placebo (with vitamin E 1200 IU/day)
Total	Total of all reporting groups

Baseline Measures

	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
Number of Participants [units: participants]	196	201	203	600
Age [units: participants]
<=18 years	0	0	0	0
Between 18 and 65 years	113	113	133	359
>=65 years	83	88	70	241
Age [units: years] Mean ± Standard Deviation	62.8 ± 9.66	63.3 ± 9.83	61.3 ± 10.5	62.5 ± 10.03
Gender [units: participants]
Female	68	62	73	203
Male	128	139	130	397
Region of Enrollment [units: participants]
United States	165	171	174	510
Canada	31	30	29	90

Outcome Measures

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1. Primary:

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 ]

Show Outcome Measure 1

2. Secondary:

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 ]

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3. Secondary:

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 ]

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4. Secondary:

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 ]

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5. Secondary:

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 ]

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6. Secondary:

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 ]

Show Outcome Measure 6

7. Secondary:

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 ]

Show Outcome Measure 7

8. Secondary:

Adverse Experiences: Back Pain [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 8

9. Secondary:

Adverse Experiences: Constipation [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 9

10. Secondary:

Adverse Experiences: Insomnia [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

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11. Secondary:

Adverse Experiences: Anxiety [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

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12. Secondary:

Adverse Experiences: Tremor [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 12

13. Secondary:

Adverse Experiences: Nasopharyngitis [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 13

14. Secondary:

Adverse Experiences: Diarrhoea [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 14

15. Secondary:

Adverse Experiences: Headache [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 15

16. Secondary:

Adverse Experiences: Urinary Tract Infection [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 16

17. Secondary:

Adverse Experiences: Nausea [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

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18. Secondary:

Adverse Experiences: Hypertension [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

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19. Secondary:

Adverse Experiences: Depression [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

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20. Secondary:

Adverse Experiences: Constipation: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 20

21. Secondary:

Adverse Experiences: Anxiety: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 21

22. Secondary:

Adverse Experiences: Back Pain: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 22

23. Secondary:

Adverse Experiences: Insomnia: Moderate/Severe [ Time Frame: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits) ]

Show Outcome Measure 23

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The planned interim analysis for futility based on the first 300 subjects has reached the pre-specified termination criterion.

Results Point of Contact:

Name/Title: M. Flint Beal, MD
Organization: Weill Medical College of Cornell University
phone: 212-746-6575
e-mail: fbeal@med.cornell.edu

Publications:

Beal MF, Henshaw DR, Jenkins BG, Rosen BR, Schulz JB. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol. 1994 Dec;36(6):882-8.

Beal MF, Matthews RT, Tieleman A, Shults CW. Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res. 1998 Feb 2;783(1):109-14.

Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 2000 Jul;23(7):298-304. Review.

Beal MF. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic Res. 2002 Apr;36(4):455-60. Review.

The NINDS NET-PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007 Jan 2;68(1):20-8.

Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, Marler JR. Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessment. Neurology. 2003 Apr 22;60(8):1234-40. Review.

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, Haas RH, Passov D, Beal MF. Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol. 1997 Aug;42(2):261-4.

Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurology. 1998 Mar;50(3):793-5.

Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50.

Shults CW. CoQ in neurodegenerative diseases. Curr Med Chem 2003; 10(19):1917-21.

Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp Neurol. 2004 Aug;188(2):491-4.

Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65.

Blatt DH, Pryor WA. High-dosage vitamin E supplementation and all-cause mortality. Ann Intern Med. 2005 Jul 19;143(2):150-1; author reply 156-8. No abstract available.

McDonald SR, Sohal RS, Forster MJ. Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med. 2005 Mar 15;38(6):729-36.

Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. Summary for patients in: Ann Intern Med. 2005 Jan 4;142(1):I40.

Meydani SN, Lau J, Dallal GE, Meydani M. High-dosage vitamin E supplementation and all-cause mortality. Ann Intern Med. 2005 Jul 19;143(2):153; author reply 156-8. No abstract available.

[No authors listed] Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group. N Engl J Med. 1993 Jan 21;328(3):176-83.

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

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