Trial Outcomes & Findings for Effects of Coenzyme Q10 (CoQ) in Parkinson Disease (NCT NCT00740714)

NCT ID: NCT00740714

Last Updated: 2013-01-31

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 600 participants
• Primary outcome timeframe: Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first
• Results posted on: 2013-01-31

Participant Flow

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.

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.

Participant milestones

Measure	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)
Overall Study STARTED	196	201	203
Overall Study Reaching Endpoint Before May 6, 2011	86	87	94
Overall Study Active Patients at Study Termination	24	12	33
Overall Study COMPLETED	179	182	174
Overall Study NOT COMPLETED	17	19	29

Reasons for withdrawal

Measure	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)
Overall Study Withdrawal by Subject	17	19	29

Baseline Characteristics

Effects of Coenzyme Q10 (CoQ) in Parkinson Disease

Baseline characteristics by cohort

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)	Total n=600 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	113 Participants n=5 Participants	113 Participants n=7 Participants	133 Participants n=5 Participants	359 Participants n=4 Participants
Age, Categorical >=65 years	83 Participants n=5 Participants	88 Participants n=7 Participants	70 Participants n=5 Participants	241 Participants n=4 Participants
Age Continuous	62.8 years STANDARD_DEVIATION 9.66 • n=5 Participants	63.3 years STANDARD_DEVIATION 9.83 • n=7 Participants	61.3 years STANDARD_DEVIATION 10.5 • n=5 Participants	62.5 years STANDARD_DEVIATION 10.03 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	62 Participants n=7 Participants	73 Participants n=5 Participants	203 Participants n=4 Participants
Sex: Female, Male Male	128 Participants n=5 Participants	139 Participants n=7 Participants	130 Participants n=5 Participants	397 Participants n=4 Participants
Region of Enrollment United States	165 participants n=5 Participants	171 participants n=7 Participants	174 participants n=5 Participants	510 participants n=4 Participants
Region of Enrollment Canada	31 participants n=5 Participants	30 participants n=7 Participants	29 participants n=5 Participants	90 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants 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))	8.01 units on a scale Standard Error .63	7.50 units on a scale Standard Error .62	6.92 units on a scale Standard Error .63

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (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 .62	-4.29 units on a scale Standard Error .62	-4.07 units on a scale Standard Error .62

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Change in Modified Rankin Scale From Baseline to 16 Months	.38 units on a scale Standard Error .05	.31 units on a scale Standard Error .05	.40 units on a scale Standard Error .05

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (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 .89	6.12 units on a scale Standard Error .87	5.57 units on a scale Standard Error .89

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (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 1.40	-0.49 units on a scale Standard Error 1.39	-3.02 units on a scale Standard Error 1.48

SECONDARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (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	.20 units on a scale Standard Error 0.03	.16 units on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: 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.

Based on samples analyzed to date

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
CoQ10 Levels in Plasma 1 month visit	3.55 ug/ml Standard Deviation 1.83	2.57 ug/ml Standard Deviation 1.29	.75 ug/ml Standard Deviation .36
CoQ10 Levels in Plasma 8 month visit	3.32 ug/ml Standard Deviation 1.93	2.67 ug/ml Standard Deviation 1.33	1.07 ug/ml Standard Deviation .83
CoQ10 Levels in Plasma 16 month visit	2.88 ug/ml Standard Deviation 2.02	2.17 ug/ml Standard Deviation 1.18	.63 ug/ml Standard Deviation .27

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with back pain

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Back Pain	9 participants	13 participants	9 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with constipation

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Constipation	7 participants	13 participants	7 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with insomnia

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Insomnia	6 participants	13 participants	6 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with anxiety

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Anxiety	12 participants	13 participants	14 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with tremor

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Tremor	10 participants	13 participants	8 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with nasopharyngitis

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Nasopharyngitis	7 participants	9 participants	3 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with diarrhoea

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Diarrhoea	6 participants	9 participants	11 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with headache

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Headache	9 participants	8 participants	11 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of patients with urinary tract infections

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Urinary Tract Infection	6 participants	8 participants	3 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with nausea

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Nausea	7 participants	7 participants	10 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with hypertension

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Hypertension	5 participants	7 participants	0 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with depression

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Depression	9 participants	6 participants	14 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with moderate/severe constipation

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Constipation: Moderate/Severe	3 participants	10 participants	3 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with moderate/severe anxiety

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Anxiety: Moderate/Severe	9 participants	9 participants	7 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with moderate/severe back pain

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Back Pain: Moderate/Severe	7 participants	9 participants	7 participants

SECONDARY outcome

Timeframe: Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)

Population: All participants were used in primary and secondary outcome analysis.

Number of participants with moderate/severe insomnia

Outcome measures

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 Participants 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 n=201 Participants Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 Participants Placebo (with vitamin E 1200 IU/day)
Adverse Experiences: Insomnia: Moderate/Severe	2 participants	9 participants	0 participants

Adverse Events

A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day

Serious events: 7 serious events

Other events: 106 other events

Deaths: 0 deaths

B. Coenzyme Q10 1200 mg/Day With Vitamin E 1200 IU/Day

Serious events: 13 serious events

Other events: 113 other events

Deaths: 0 deaths

C. Placebo With Vitamin E 1200 IU/Day

Serious events: 13 serious events

Other events: 108 other events

Deaths: 0 deaths

Serious adverse events

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 participants at risk 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 n=201 participants at risk Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 participants at risk Placebo (with vitamin E 1200 IU/day)
Surgical and medical procedures Pacemaker battery replacement	1.0% 2/196 • Number of events 2 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Psychiatric disorders Depression	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Cervical radiculopathy	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Back pain	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Bowel obstruction	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Vertigo	0.51% 1/196 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Injury, poisoning and procedural complications Accident with fractures	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Surgical and medical procedures Total knee replacement	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 2 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Surgical and medical procedures Gastric banding	0.51% 1/196 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Cardiac disorders Chest pain	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Reproductive system and breast disorders Pelvic floor dysfunction	0.00% 0/68 • Adverse events data were collected for a period of 2 years and 7 months.	1.6% 1/62 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/73 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Spinal stenosis	0.51% 1/196 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Surgical and medical procedures Cardiac catheterization	0.51% 1/196 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	— 0/0 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Gastero-intestinal bleed	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Multiple myeloma	0.51% 1/196 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Renal and urinary disorders Prostatitis	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Renal and urinary disorders Prostate cancer progression	0.78% 1/128 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/139 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/130 • Adverse events data were collected for a period of 2 years and 7 months.
Reproductive system and breast disorders Breast cancer	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Pulmonary embolism	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Renal and urinary disorders Benign prostatic hypertrophy	0.00% 0/128 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/139 • Adverse events data were collected for a period of 2 years and 7 months.	0.77% 1/130 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Pneumonia	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.99% 2/203 • Number of events 2 • Adverse events data were collected for a period of 2 years and 7 months.
Surgical and medical procedures Transurethral resection of the prostate	0.00% 0/128 • Adverse events data were collected for a period of 2 years and 7 months.	0.72% 1/139 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/130 • Adverse events data were collected for a period of 2 years and 7 months.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Sudden death	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Infections and infestations Dental infection	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
Respiratory, thoracic and mediastinal disorders Hypersensitivity pneumonitis	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 2 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Colon cancer	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Dehydration	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.49% 1/203 • Number of events 2 • Adverse events data were collected for a period of 2 years and 7 months.
Cardiac disorders Myocardial infarction	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Cardiac disorders Atrial fibrillation	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Subarachnoid hemorrhage	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/201 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Accident with fractures and head trauma	0.00% 0/196 • Adverse events data were collected for a period of 2 years and 7 months.	0.50% 1/201 • Number of events 1 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.

Other adverse events

Measure	A. Coenzyme Q10 2400 mg/Day With Vitamin E 1200 IU/Day n=196 participants at risk 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 n=201 participants at risk Randomized to active treatment (Coenzyme Q10 1200 mg/day with vitamin E 1200 IU/day)	C. Placebo With Vitamin E 1200 IU/Day n=203 participants at risk Placebo (with vitamin E 1200 IU/day)
Nervous system disorders Back pain	4.6% 9/196 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.	6.5% 13/201 • Number of events 13 • Adverse events data were collected for a period of 2 years and 7 months.	4.4% 9/203 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Constipation	3.6% 7/196 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	6.5% 13/201 • Number of events 13 • Adverse events data were collected for a period of 2 years and 7 months.	3.4% 7/203 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Insomnia	3.1% 6/196 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	6.5% 13/201 • Number of events 13 • Adverse events data were collected for a period of 2 years and 7 months.	3.0% 6/203 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.
Psychiatric disorders Anxiety	6.1% 12/196 • Number of events 12 • Adverse events data were collected for a period of 2 years and 7 months.	6.5% 13/201 • Number of events 13 • Adverse events data were collected for a period of 2 years and 7 months.	6.9% 14/203 • Number of events 14 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Tremor	5.1% 10/196 • Number of events 10 • Adverse events data were collected for a period of 2 years and 7 months.	6.5% 13/201 • Number of events 13 • Adverse events data were collected for a period of 2 years and 7 months.	3.9% 8/203 • Number of events 8 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Nasopharyngitis	3.6% 7/196 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	4.5% 9/201 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.	1.5% 3/203 • Number of events 3 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Diarrhea	3.1% 6/196 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	4.5% 9/201 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.	5.4% 11/203 • Number of events 11 • Adverse events data were collected for a period of 2 years and 7 months.
General disorders Headache	4.6% 9/196 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.	4.0% 8/201 • Number of events 8 • Adverse events data were collected for a period of 2 years and 7 months.	5.4% 11/203 • Number of events 11 • Adverse events data were collected for a period of 2 years and 7 months.
Renal and urinary disorders Urinary tract infection	3.1% 6/196 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	4.0% 8/201 • Number of events 8 • Adverse events data were collected for a period of 2 years and 7 months.	1.5% 3/203 • Number of events 3 • Adverse events data were collected for a period of 2 years and 7 months.
Gastrointestinal disorders Nausea	3.6% 7/196 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	3.5% 7/201 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	4.9% 10/203 • Number of events 10 • Adverse events data were collected for a period of 2 years and 7 months.
Vascular disorders Hypertension	2.6% 5/196 • Number of events 5 • Adverse events data were collected for a period of 2 years and 7 months.	3.5% 7/201 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	0.00% 0/203 • Adverse events data were collected for a period of 2 years and 7 months.
Psychiatric disorders Depression	4.6% 9/196 • Number of events 9 • Adverse events data were collected for a period of 2 years and 7 months.	3.0% 6/201 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	6.9% 14/203 • Number of events 14 • Adverse events data were collected for a period of 2 years and 7 months.
Nervous system disorders Dizziness	3.6% 7/196 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.	3.0% 6/201 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	2.5% 5/203 • Number of events 5 • Adverse events data were collected for a period of 2 years and 7 months.
Injury, poisoning and procedural complications Fall	3.1% 6/196 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	3.0% 6/201 • Number of events 6 • Adverse events data were collected for a period of 2 years and 7 months.	3.4% 7/203 • Number of events 7 • Adverse events data were collected for a period of 2 years and 7 months.

Additional Information

M. Flint Beal, MD

Weill Medical College of Cornell University

Phone: 212-746-6575

Email: fbeal@med.cornell.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place