Coenzyme Q10 in Huntington's Disease (HD) (2CARE)

• ClinicalTrials.gov Identifier: NCT00608881
• Recruitment Status: Terminated
• First Posted: February 6, 2008
• Results First Posted: March 30, 2016
• Last Update Posted: March 30, 2016
• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); University of Rochester
• Information provided by (Responsible Party): Merit E. Cudkowicz, MD, Massachusetts General Hospital

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Huntington's Disease
• Interventions: Drug: coenzyme Q10; Other: placebo
• Enrollment: 609

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Period Title: Overall Study
Started	303	306
Completed	224	240
Not Completed	79	66
Reason Not Completed
Death	22	13
Adverse Event	5	3
Lost to Follow-up	28	14
Withdrawal by Subject	18	29
Physician Decision	5	5
Institutionalized	1	2

Baseline Characteristics

Arm/Group Title		A - Coenzyme Q10 2400 mg/Day	B - Placebo	Total
Arm/Group Description		Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance	Total of all reporting groups
Overall Number of Baseline Participants		303	306	609
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	303 participants	306 participants	609 participants
		50.5 (11.9)	50.7 (11.6)	50.6 (11.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	303 participants	306 participants	609 participants
	Female	149 49.2%	164 53.6%	313 51.4%
	Male	154 50.8%	142 46.4%	296 48.6%

Outcome Measures

1. Primary Outcome

Title	Joint Rank (Combination of Time to Death (for Subjects Who Died) and Change in Total Functional Capacity Score (TFC) From Baseline to Month 60 (for Subjects Who Survived))
Description	The primary outcome variable at the start of the trial was the change in TFC score from baseline to Month 60. The Data and Safety Monitoring Board recommended to the trial leadership that they reconsider how they accommodate missing data from subjects who die in their primary analysis of the change in TFC score. Based on these recommendations, the trial leadership changed the primary analysis to that of a joint rank approach. TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Mean (Standard Deviation); Unit of Measure: rank
	303.3 (173.1)	306.7 (179.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	In this joint rank analysis, subjects are ranked from worst to best outcome with subjects who die being assigned the worst ranks (and ranked according to the time of death) and subjects who survive being ranked more favorably in the order of the change from baseline to Month 60 in TFC score.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	π hat
	Estimated Value	0.494
	Confidence Interval	(2-Sided) 95%; 0.454 to 0.534
	Estimation Comments	π hat is the estimate of the probability π that a randomly selected subject treated with CoQ has a better outcome than a randomly selected subject treated with placebo. Under the null hypothesis of no effect of CoQ, π = 0.50.

2. Secondary Outcome

Title	Change in Total Functional Capacity (TFC) Score From Baseline to Month 60
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-4.53 (0.25)	-4.76 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.23
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.91
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change in Functional Checklist Score From Baseline to Month 60
Description	The functional assessment checklist includes 25 questions about common daily tasks. A score of 1 is given for each "yes" reply and a score of 0 is given for each "no" reply (scale range is 0-25). Higher scores indicate better functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Mean (Standard Error); Unit of Measure: units on a scale
	-7.93 (0.55)	-8.02 (0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -1.40 to 1.58
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change in Independence Scale Score From Baseline to Month 60
Description	The independence scale assesses independence on a 0 to 100 scale with higher scores indicating better functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Mean (Standard Error); Unit of Measure: units on a scale
	-26.30 (1.92)	-24.86 (1.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.44
	Confidence Interval	(2-Sided) 95%; -6.68 to 3.79
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change in Total Motor Score From Baseline to Month 60
Description	The motor section of the Unified Huntington's Disease Rating Scale (UHDRS) assesses motor features of Huntington disease with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. The total motor score is the sum of all the individual motor ratings, with higher scores (124) indicating more severe motor impairment than lower scores. The score ranges from 0 to 124.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	18.06 (1.22)	19.18 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 95%; -4.40 to 2.16
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change in Behavioral Frequency Score From Baseline to Month 60
Description	The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. A total score was calculated by summing up all the individual behavioral frequency items (range 0-56) with higher scores representing more severe behavioral impairment.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	1.39 (0.55)	1.43 (0.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -1.48 to 1.39
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change in Behavioral Frequency x Severity Score From Baseline to Month 60
Description	The Unified Huntington's Disease Rating Scale (UHDRS) behavioral subscale assesses frequency and severity of psychiatric-related symptoms, including depressed mood, apathy, low self-esteem/guilt, suicidal thoughts, anxiety, irritable behavior, aggressive behavior, obsessional thinking, compulsive behavior, delusions, and hallucinations. The total score is the sum of the product of the individual behavioral frequency and severity items (range 0-176) with higher scores representing more severe behavioral impairment.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	4.29 (1.52)	5.06 (1.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -4.78 to 3.23
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60
Description	The SDMT assesses attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The score is the number of correctly paired abstract symbols and specific numbers in 90 seconds with higher scores indicating better cognitive functioning.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-10.95 (0.66)	-11.36 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.41
	Confidence Interval	(2-Sided) 95%; -1.32 to 2.14
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Change in Verbal Fluency Test From Baseline to Month 60
Description	The verbal fluency test is typically considered a measure of executive function. The score is the number of correct words produced across three 1-minute trials.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-5.07 (0.79)	-4.47 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.60
	Confidence Interval	(2-Sided) 95%; -2.71 to 1.51
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Change in Stroop Interference Test - Color Naming From Baseline to Month 60
Description	Stroop Interference Test - color naming score is the total number of correct colors identified in 45 seconds and reflects processing speed.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-14.21 (1.00)	-14.51 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.29
	Confidence Interval	(2-Sided) 95%; -2.28 to 2.87
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change in Stroop Interference Test - Word Reading From Baseline to Month 60
Description	Stroop Interference Test - word reading score is the total number of correct words read in 45 seconds and reflects processing speed.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-15.25 (1.36)	-19.13 (1.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.88
	Confidence Interval	(2-Sided) 95%; 0.31 to 7.44
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Change in Stroop Interference Test - Interference From Baseline to Month 60
Description	Stroop Interference Test - interference score is the total number of correct items identified in 45 seconds and reflects an executive measure of inhibitory ability.
Time Frame	Baseline and Month 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Least Squares Mean (Standard Error); Unit of Measure: units on a scale
	-7.57 (0.81)	-8.61 (0.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; -1.10 to 3.18
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Time to a Two-Point Decline in TFC Score or Death
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Median (95% Confidence Interval); Unit of Measure: days to event
	553; (545 to 728)	549; (395 to 726)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.20
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Time to a Three-Point Decline in TFC Score or Death
Description	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Median (95% Confidence Interval); Unit of Measure: days to event
	917; (760 to 1092)	911; (737 to 1092)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	A - Coenzyme Q10 2400 mg/Day, B - Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.15
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Number Completing Study at Assigned Dosage Level
Description	[Not Specified]
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description:	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
Overall Number of Participants Analyzed	303	306
Measure Type: Number; Unit of Measure: participants completing study on drug
	98	108

Adverse Events

Time Frame	5 years
Adverse Event Reporting Description	Adverse events were assessed at each visit by recording all voluntary complaints of the subject and by assessment of clinical features. Subjects were questioned regarding the occurrence of any adverse event since the last visit. All adverse events were recorded on an Adverse Event Log case report form.
Arm/Group Title	A - Coenzyme Q10 2400 mg/Day	B - Placebo
Arm/Group Description	Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	Randomized to placebo placebo: an inactive substance
All-Cause Mortality
	A - Coenzyme Q10 2400 mg/Day	B - Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	A - Coenzyme Q10 2400 mg/Day	B - Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	76/303 (25.08%)	83/306 (27.12%)
Blood and lymphatic system disorders
NEUTROPENIA † 1	1/303 (0.33%)	0/306 (0.00%)
Cardiac disorders
ANGINA UNSTABLE † 1	0/303 (0.00%)	1/306 (0.33%)
ATRIAL FIBRILLATION † 1	1/303 (0.33%)	0/306 (0.00%)
CARDIAC ARREST † 1	0/303 (0.00%)	1/306 (0.33%)
CORONARY ARTERY DISEASE † 1	0/303 (0.00%)	1/306 (0.33%)
CORONARY ARTERY OCCLUSION † 1	1/303 (0.33%)	0/306 (0.00%)
MYOCARDIAL INFARCTION † 1	0/303 (0.00%)	3/306 (0.98%)
Congenital, familial and genetic disorders
HUNTINGTON'S DISEASE † 1	2/303 (0.66%)	2/306 (0.65%)
Ear and labyrinth disorders
VERTIGO † 1	0/303 (0.00%)	1/306 (0.33%)
Eye disorders
RETINAL DETACHMENT † 1	0/303 (0.00%)	1/306 (0.33%)
Gastrointestinal disorders
COLITIS † 1	0/303 (0.00%)	1/306 (0.33%)
CROHN'S DISEASE † 1	0/303 (0.00%)	1/306 (0.33%)
DIARRHOEA † 1	1/303 (0.33%)	0/306 (0.00%)
DYSPHAGIA † 1	2/303 (0.66%)	2/306 (0.65%)
HAEMORRHOIDS † 1	1/303 (0.33%)	0/306 (0.00%)
INTESTINAL OBSTRUCTION † 1	1/303 (0.33%)	1/306 (0.33%)
LARGE INTESTINAL OBSTRUCTION † 1	1/303 (0.33%)	0/306 (0.00%)
PEPTIC ULCER † 1	1/303 (0.33%)	0/306 (0.00%)
SMALL INTESTINAL OBSTRUCTION † 1	1/303 (0.33%)	0/306 (0.00%)
VOMITING † 1	1/303 (0.33%)	0/306 (0.00%)
General disorders
CHEST PAIN † 1	2/303 (0.66%)	0/306 (0.00%)
DRUG WITHDRAWAL SYNDROME † 1	0/303 (0.00%)	1/306 (0.33%)
NON-CARDIAC CHEST PAIN † 1	1/303 (0.33%)	0/306 (0.00%)
Hepatobiliary disorders
CHOLECYSTITIS † 1	1/303 (0.33%)	1/306 (0.33%)
CHOLELITHIASIS † 1	1/303 (0.33%)	0/306 (0.00%)
Immune system disorders
DRUG HYPERSENSITIVITY † 1	0/303 (0.00%)	1/306 (0.33%)
Infections and infestations
ABSCESS † 1	1/303 (0.33%)	0/306 (0.00%)
ARTHRITIS INFECTIVE † 1	0/303 (0.00%)	1/306 (0.33%)
BACTERAEMIA † 1	0/303 (0.00%)	1/306 (0.33%)
CELLULITIS † 1	0/303 (0.00%)	1/306 (0.33%)
DIVERTICULITIS † 1	0/303 (0.00%)	2/306 (0.65%)
GASTROENTERITIS † 1	0/303 (0.00%)	1/306 (0.33%)
NECROTISING FASCIITIS † 1	1/303 (0.33%)	0/306 (0.00%)
PNEUMONIA † 1	2/303 (0.66%)	5/306 (1.63%)
SEPSIS † 1	1/303 (0.33%)	0/306 (0.00%)
SKIN GRAFT INFECTION † 1	0/303 (0.00%)	1/306 (0.33%)
STAPHYLOCOCCAL BACTERAEMIA † 1	1/303 (0.33%)	0/306 (0.00%)
STAPHYLOCOCCAL INFECTION † 1	1/303 (0.33%)	0/306 (0.00%)
URINARY TRACT INFECTION † 1	0/303 (0.00%)	2/306 (0.65%)
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE † 1	1/303 (0.33%)	1/306 (0.33%)
ANKLE FRACTURE † 1	1/303 (0.33%)	1/306 (0.33%)
COMMINUTED FRACTURE † 1	1/303 (0.33%)	0/306 (0.00%)
CONCUSSION † 1	0/303 (0.00%)	1/306 (0.33%)
FACIAL BONES FRACTURE † 1	0/303 (0.00%)	1/306 (0.33%)
FALL † 1	3/303 (0.99%)	5/306 (1.63%)
FEMUR FRACTURE † 1	1/303 (0.33%)	0/306 (0.00%)
FIBULA FRACTURE † 1	1/303 (0.33%)	0/306 (0.00%)
FRACTURE † 1	2/303 (0.66%)	0/306 (0.00%)
HIP FRACTURE † 1	1/303 (0.33%)	2/306 (0.65%)
INJURY † 1	1/303 (0.33%)	0/306 (0.00%)
INTENTIONAL OVERDOSE † 1	1/303 (0.33%)	0/306 (0.00%)
LIMB TRAUMATIC AMPUTATION † 1	1/303 (0.33%)	0/306 (0.00%)
ROAD TRAFFIC ACCIDENT † 1	1/303 (0.33%)	1/306 (0.33%)
SPINAL COMPRESSION FRACTURE † 1	0/303 (0.00%)	1/306 (0.33%)
SUBDURAL HAEMATOMA † 1	1/303 (0.33%)	5/306 (1.63%)
TIBIA FRACTURE † 1	1/303 (0.33%)	0/306 (0.00%)
TRAUMATIC FRACTURE † 1	0/303 (0.00%)	1/306 (0.33%)
UPPER LIMB FRACTURE † 1	0/303 (0.00%)	1/306 (0.33%)
WRIST FRACTURE † 1	1/303 (0.33%)	0/306 (0.00%)
Metabolism and nutrition disorders
DEHYDRATION † 1	1/303 (0.33%)	1/306 (0.33%)
DIABETIC KETOACIDOSIS † 1	1/303 (0.33%)	0/306 (0.00%)
HYPERGLYCAEMIA † 1	0/303 (0.00%)	1/306 (0.33%)
HYPONATRAEMIA † 1	1/303 (0.33%)	0/306 (0.00%)
Musculoskeletal and connective tissue disorders
NECK PAIN † 1	0/303 (0.00%)	2/306 (0.65%)
NOSE DEFORMITY † 1	0/303 (0.00%)	1/306 (0.33%)
OSTEOARTHRITIS † 1	0/303 (0.00%)	1/306 (0.33%)
OSTEOPOROSIS † 1	1/303 (0.33%)	0/306 (0.00%)
RHABDOMYOLYSIS † 1	1/303 (0.33%)	0/306 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA † 1	0/303 (0.00%)	1/306 (0.33%)
BRAIN NEOPLASM † 1	1/303 (0.33%)	0/306 (0.00%)
BREAST CANCER † 1	1/303 (0.33%)	2/306 (0.65%)
CARCINOID TUMOUR † 1	1/303 (0.33%)	0/306 (0.00%)
COLON CANCER METASTATIC † 1	0/303 (0.00%)	1/306 (0.33%)
GLIOMA † 1	1/303 (0.33%)	0/306 (0.00%)
INFLAMMATORY CARCINOMA OF THE BREAST † 1	0/303 (0.00%)	1/306 (0.33%)
LUNG NEOPLASM MALIGNANT † 1	1/303 (0.33%)	1/306 (0.33%)
MANTLE CELL LYMPHOMA † 1	0/303 (0.00%)	1/306 (0.33%)
PROSTATE CANCER † 1	0/303 (0.00%)	1/306 (0.33%)
UTERINE LEIOMYOMA † 1	0/303 (0.00%)	1/306 (0.33%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT † 1	1/303 (0.33%)	0/306 (0.00%)
CHOREA † 1	0/303 (0.00%)	1/306 (0.33%)
CONVULSION † 1	0/303 (0.00%)	2/306 (0.65%)
HAEMORRHAGE INTRACRANIAL † 1	0/303 (0.00%)	1/306 (0.33%)
LOSS OF CONSCIOUSNESS † 1	0/303 (0.00%)	2/306 (0.65%)
PARKINSONISM † 1	1/303 (0.33%)	0/306 (0.00%)
SYNCOPE † 1	3/303 (0.99%)	2/306 (0.65%)
TOXIC ENCEPHALOPATHY † 1	0/303 (0.00%)	1/306 (0.33%)
TRANSIENT ISCHAEMIC ATTACK † 1	0/303 (0.00%)	1/306 (0.33%)
Psychiatric disorders
ABNORMAL BEHAVIOUR † 1	1/303 (0.33%)	0/306 (0.00%)
AGGRESSION † 1	2/303 (0.66%)	2/306 (0.65%)
AGITATION † 1	1/303 (0.33%)	1/306 (0.33%)
ANXIETY † 1	1/303 (0.33%)	1/306 (0.33%)
COMPLETED SUICIDE † 1	4/303 (1.32%)	1/306 (0.33%)
CONFUSIONAL STATE † 1	0/303 (0.00%)	1/306 (0.33%)
DELIRIUM † 1	1/303 (0.33%)	0/306 (0.00%)
DELUSION † 1	1/303 (0.33%)	2/306 (0.65%)
DEPRESSION † 1	2/303 (0.66%)	6/306 (1.96%)
HALLUCINATION, AUDITORY † 1	1/303 (0.33%)	1/306 (0.33%)
MAJOR DEPRESSION † 1	2/303 (0.66%)	0/306 (0.00%)
PANIC ATTACK † 1	1/303 (0.33%)	0/306 (0.00%)
PARANOIA † 1	1/303 (0.33%)	0/306 (0.00%)
PSYCHOTIC BEHAVIOUR † 1	1/303 (0.33%)	0/306 (0.00%)
PSYCHOTIC DISORDER † 1	2/303 (0.66%)	1/306 (0.33%)
SUICIDAL BEHAVIOUR † 1	1/303 (0.33%)	1/306 (0.33%)
SUICIDAL IDEATION † 1	3/303 (0.99%)	7/306 (2.29%)
SUICIDE ATTEMPT † 1	10/303 (3.30%)	8/306 (2.61%)
Renal and urinary disorders
NEPHROLITHIASIS † 1	0/303 (0.00%)	1/306 (0.33%)
RENAL FAILURE † 1	0/303 (0.00%)	2/306 (0.65%)
Reproductive system and breast disorders
UTERINE PROLAPSE † 1	1/303 (0.33%)	0/306 (0.00%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE † 1	1/303 (0.33%)	0/306 (0.00%)
ASPIRATION † 1	0/303 (0.00%)	1/306 (0.33%)
ASTHMA † 1	1/303 (0.33%)	1/306 (0.33%)
BRONCHIECTASIS † 1	0/303 (0.00%)	1/306 (0.33%)
COUGH † 1	1/303 (0.33%)	0/306 (0.00%)
PNEUMONIA ASPIRATION † 1	1/303 (0.33%)	0/306 (0.00%)
UPPER AIRWAY OBSTRUCTION † 1	0/303 (0.00%)	1/306 (0.33%)
Surgical and medical procedures
CORONARY ARTERY BYPASS † 1	1/303 (0.33%)	0/306 (0.00%)
DEEP BRAIN STIMULATION † 1	0/303 (0.00%)	1/306 (0.33%)
HAEMORRHOID OPERATION † 1	1/303 (0.33%)	0/306 (0.00%)
HERNIA REPAIR † 1	0/303 (0.00%)	1/306 (0.33%)
HIP ARTHROPLASTY † 1	1/303 (0.33%)	0/306 (0.00%)
HYSTERECTOMY † 1	0/303 (0.00%)	1/306 (0.33%)
KNEE ARTHROPLASTY † 1	0/303 (0.00%)	1/306 (0.33%)
SHOULDER ARTHROPLASTY † 1	1/303 (0.33%)	0/306 (0.00%)
SPINAL LAMINECTOMY † 1	1/303 (0.33%)	0/306 (0.00%)
SURGERY † 1	1/303 (0.33%)	0/306 (0.00%)
THYROIDECTOMY † 1	0/303 (0.00%)	1/306 (0.33%)
Vascular disorders
HYPOTENSION † 1	2/303 (0.66%)	0/306 (0.00%)
ILIAC ARTERY OCCLUSION † 1	1/303 (0.33%)	0/306 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	A - Coenzyme Q10 2400 mg/Day	B - Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	276/303 (91.09%)	280/306 (91.50%)
Gastrointestinal disorders
CONSTIPATION † 1	26/303 (8.58%)	22/306 (7.19%)
DIARRHOEA † 1	36/303 (11.88%)	43/306 (14.05%)
DYSPHAGIA † 1	25/303 (8.25%)	21/306 (6.86%)
NAUSEA † 1	31/303 (10.23%)	24/306 (7.84%)
VOMITING † 1	25/303 (8.25%)	23/306 (7.52%)
General disorders
FATIGUE † 1	19/303 (6.27%)	16/306 (5.23%)
Infections and infestations
BRONCHITIS † 1	16/303 (5.28%)	19/306 (6.21%)
INFLUENZA † 1	21/303 (6.93%)	17/306 (5.56%)
NASOPHARYNGITIS † 1	27/303 (8.91%)	34/306 (11.11%)
SINUSITIS † 1	14/303 (4.62%)	19/306 (6.21%)
UPPER RESPIRATORY TRACT INFECTION † 1	23/303 (7.59%)	27/306 (8.82%)
URINARY TRACT INFECTION † 1	33/303 (10.89%)	46/306 (15.03%)
Injury, poisoning and procedural complications
CONTUSION † 1	10/303 (3.30%)	21/306 (6.86%)
FALL † 1	72/303 (23.76%)	84/306 (27.45%)
LACERATION † 1	14/303 (4.62%)	23/306 (7.52%)
Investigations
WEIGHT DECREASED † 1	25/303 (8.25%)	33/306 (10.78%)
Nervous system disorders
BALANCE DISORDER † 1	19/303 (6.27%)	21/306 (6.86%)
CHOREA † 1	37/303 (12.21%)	44/306 (14.38%)
DIZZINESS † 1	15/303 (4.95%)	16/306 (5.23%)
HEADACHE † 1	17/303 (5.61%)	14/306 (4.58%)
Psychiatric disorders
ANXIETY † 1	36/303 (11.88%)	42/306 (13.73%)
DEPRESSION † 1	61/303 (20.13%)	66/306 (21.57%)
INSOMNIA † 1	35/303 (11.55%)	64/306 (20.92%)
IRRITABILITY † 1	36/303 (11.88%)	38/306 (12.42%)
Respiratory, thoracic and mediastinal disorders
COUGH † 1	13/303 (4.29%)	19/306 (6.21%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.1

Limitations and Caveats

An interim analysis for futility revealed a conditional power of < 5% for the primary analysis, and the trial was halted in July, 2014. Only data collected prior to this time were included in the final analyses.

More Information

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.

Results Point of Contact

• Name/Title: Dr. Merit Cudkowicz
• Organization: Massachusetts General Hospital
• Phone: 617-726-0813
• EMail: mcudkowicz@partners.org

Publications:

Kowall N, Ferrante R, Martin J. Patterns of cell loss in Huntington's disease. Trends in Neurosciences 1987;10:24-29.

Riley D, Lang A. Movement Disorders. In: Bradley W, Daroff R, Fenichel G, eds. Neurology in Clinical Practice. The Neurological Disorders. Boston: Butterworth-Heinemann, 1991: 1563-1601.

Adams P, Falek A, Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988 Nov;43(5):695-704.

Conneally PM. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984 May;36(3):506-26.

Harper PS. The epidemiology of Huntington's disease. Hum Genet. 1992 Jun;89(4):365-76. doi: 10.1007/BF00194305.

Tanner CM, Goldman SM. Epidemiology of movement disorders. Curr Opin Neurol. 1994 Aug;7(4):340-5. doi: 10.1097/00019052-199408000-00011. No abstract available.

Young AB, Shoulson I, Penney JB, Starosta-Rubinstein S, Gomez F, Travers H, Ramos-Arroyo MA, Snodgrass SR, Bonilla E, Moreno H, et al. Huntington's disease in Venezuela: neurologic features and functional decline. Neurology. 1986 Feb;36(2):244-9. doi: 10.1212/wnl.36.2.244.

Bruyn G. Huntington's chorea: Historical clinical and laboratory synopsis. In: Vinken P, Bruyn G, eds. Handbook of Clinical Neurology. Amsterdam, 1968: 298-378.

Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington's disease. Neurology. 1983 Oct;33(10):1268-75. doi: 10.1212/wnl.33.10.1268.

Caine ED, Hunt RD, Weingartner H, Ebert MH. Huntington's dementia. Clinical and neuropsychological features. Arch Gen Psychiatry. 1978 Mar;35(3):377-84. doi: 10.1001/archpsyc.1978.01770270127013.

Bamford KA, Caine ED, Kido DK, Plassche WM, Shoulson I. Clinical-pathologic correlation in Huntington's disease: a neuropsychological and computed tomography study. Neurology. 1989 Jun;39(6):796-801. doi: 10.1212/wnl.39.6.796.

Sorensen SA, Fenger K. Causes of death in patients with Huntington's disease and in unaffected first degree relatives. J Med Genet. 1992 Dec;29(12):911-4. doi: 10.1136/jmg.29.12.911.

Oliver JE. Huntington's chorea in Northamptonshire. Br J Psychiatry. 1970 Mar;116(532):241-53. doi: 10.1192/bjp.116.532.241. No abstract available.

Greenamyre J, Shoulson I. Huntington's Disease. In: Calne D, ed. Neurodegenerative Diseases. Philadelphia: WB Saunders, 1994: 685-704.

Shoulson I, Fahn S. Huntington disease: clinical care and evaluation. Neurology. 1979 Jan;29(1):1-3. doi: 10.1212/wnl.29.1.1. No abstract available.

Feigin A, Kieburtz K, Bordwell K, Como P, Steinberg K, Sotack J, Zimmerman C, Hickey C, Orme C, Shoulson I. Functional decline in Huntington's disease. Mov Disord. 1995 Mar;10(2):211-4. doi: 10.1002/mds.870100213.

Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK, Pettengill FK, Bird ED. Factors associated with slow progression in Huntington's disease. Arch Neurol. 1991 Aug;48(8):800-4. doi: 10.1001/archneur.1991.00530200036015.

Penney JB Jr, Young AB, Shoulson I, Starosta-Rubenstein S, Snodgrass SR, Sanchez-Ramos J, Ramos-Arroyo M, Gomez F, Penchaszadeh G, Alvir J, et al. Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov Disord. 1990;5(2):93-9. doi: 10.1002/mds.870050202.

Young AB, Penney JB, Starosta-Rubinstein S, Markel DS, Berent S, Giordani B, Ehrenkaufer R, Jewett D, Hichwa R. PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol. 1986 Sep;20(3):296-303. doi: 10.1002/ana.410200305.

Kido D, Shoulson I, Manzione J, Harnish P. Measurement of caudate nucleus and putamen atrophy in patients with Huntington's disease. Neuroradiology 1991;33:604-606.

Mazziotta JC. Huntington's disease: studies with structural imaging techniques and positron emission tomography. Semin Neurol. 1989 Dec;9(4):360-9. doi: 10.1055/s-2008-1041346. No abstract available.

Beal MF, Ferrante RJ. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci. 2004 May;5(5):373-84. doi: 10.1038/nrn1386. No abstract available.

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.

Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, Cooper JM, Schapira AH. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol. 2000 Jan;47(1):80-6. doi: 10.1002/1531-8249(200001)47:13.3.co;2-b.

Cha JH. Transcriptional dysregulation in Huntington's disease. Trends Neurosci. 2000 Sep;23(9):387-92. doi: 10.1016/s0166-2236(00)01609-x.

Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JH, Friedlander RM. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999 May 20;399(6733):263-7. doi: 10.1038/20446.

Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. doi: 10.1038/77528.

Beal MF, Hyman BT, Koroshetz W. Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci. 1993 Apr;16(4):125-31. doi: 10.1016/0166-2236(93)90117-5.

Wellington CL, Ellerby LM, Hackam AS, Margolis RL, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem. 1998 Apr 10;273(15):9158-67. doi: 10.1074/jbc.273.15.9158.

Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, Beal MF. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7105-9. doi: 10.1073/pnas.92.15.7105.

Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol. 1996 Mar;39(3):385-9. doi: 10.1002/ana.410390317.

Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol. 1997 Feb;41(2):160-5. doi: 10.1002/ana.410410206.

Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr, Greenamyre JT, Snyder SH, Ross CA. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med. 1999 Oct;5(10):1194-8. doi: 10.1038/13518.

Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology. 1993 Dec;43(12):2689-95. doi: 10.1212/wnl.43.12.2689.

Lodi R, Schapira AH, Manners D, Styles P, Wood NW, Taylor DJ, Warner TT. Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann Neurol. 2000 Jul;48(1):72-6.

Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci. 2002 Aug;5(8):731-6. doi: 10.1038/nn884.

Gines S, Seong IS, Fossale E, Ivanova E, Trettel F, Gusella JF, Wheeler VC, Persichetti F, MacDonald ME. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum Mol Genet. 2003 Mar 1;12(5):497-508. doi: 10.1093/hmg/ddg046.

Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol. 1997 May;41(5):646-53. doi: 10.1002/ana.410410514.

Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389-97. doi: 10.1523/JNEUROSCI.20-12-04389.2000.

Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci. 2002 Mar 1;22(5):1592-9. doi: 10.1523/JNEUROSCI.22-05-01592.2002.

Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67. doi: 10.1046/j.1471-4159.2003.01706.x.

Schilling G, Coonfield ML, Ross CA, Borchelt DR. Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model. Neurosci Lett. 2001 Nov 27;315(3):149-53. doi: 10.1016/s0304-3940(01)02326-6.

Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8892-7. doi: 10.1073/pnas.95.15.8892.

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. doi: 10.1002/ana.410360613.

Pepping J. Coenzyme Q10. Am J Health Syst Pharm. 1999 Mar 15;56(6):519-21. doi: 10.1093/ajhp/56.6.519. No abstract available.

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Peyser CE, Folstein M, Chase GA, Starkstein S, Brandt J, Cockrell JR, Bylsma F, Coyle JT, McHugh PR, Folstein SE. Trial of d-alpha-tocopherol in Huntington's disease. Am J Psychiatry. 1995 Dec;152(12):1771-5. doi: 10.1176/ajp.152.12.1771.

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

McGarry A, Auinger P, Kieburtz KD, Bredlau AL, Hersch SM, Rosas HD. Suicidality Risk Factors Across the CARE-HD, 2CARE, and CREST-E Clinical Trials in Huntington Disease. Neurol Clin Pract. 2022 Apr;12(2):131-138. doi: 10.1212/CPJ.0000000000001161.

McGarry A, McDermott MP, Kieburtz K, Fung WLA, McCusker E, Peng J, de Blieck EA, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. Risk factors for suicidality in Huntington disease: An analysis of the 2CARE clinical trial. Neurology. 2019 Apr 2;92(14):e1643-e1651. doi: 10.1212/WNL.0000000000007244. Epub 2019 Mar 8.

McGarry A, McDermott M, Kieburtz K, de Blieck EA, Beal F, Marder K, Ross C, Shoulson I, Gilbert P, Mallonee WM, Guttman M, Wojcieszek J, Kumar R, LeDoux MS, Jenkins M, Rosas HD, Nance M, Biglan K, Como P, Dubinsky RM, Shannon KM, O'Suilleabhain P, Chou K, Walker F, Martin W, Wheelock VL, McCusker E, Jankovic J, Singer C, Sanchez-Ramos J, Scott B, Suchowersky O, Factor SA, Higgins DS Jr, Molho E, Revilla F, Caviness JN, Friedman JH, Perlmutter JS, Feigin A, Anderson K, Rodriguez R, McFarland NR, Margolis RL, Farbman ES, Raymond LA, Suski V, Kostyk S, Colcher A, Seeberger L, Epping E, Esmail S, Diaz N, Fung WL, Diamond A, Frank S, Hanna P, Hermanowicz N, Dure LS, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017 Jan 10;88(2):152-159. doi: 10.1212/WNL.0000000000003478. Epub 2016 Dec 2.

• Responsible Party: Merit E. Cudkowicz, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00608881
• Other Study ID Numbers: 2CARE 01.00; 5U01NS052592 ( U.S. NIH Grant/Contract ); 5R01NS052619 ( U.S. NIH Grant/Contract )
• First Submitted: February 4, 2008
• First Posted: February 6, 2008
• Results First Submitted: December 7, 2015
• Results First Posted: March 30, 2016
• Last Update Posted: March 30, 2016