Coenzyme Q10 in Huntington's Disease (HD)

Status

Terminated

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00608881

Acronym

2CARE

Enrollment

609

Registered

2008-02-06

Start date

2008-03-31

Completion date

2015-05-31

Last updated

2016-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Huntington's Disease

Keywords

Huntington's disease, Huntington disease, HD, coenzyme Q10, CoQ

Brief summary

The goals of this trial are to determine if coenzyme Q10 is effective in slowing the worsening symptoms of Huntington's disease and to learn about the safety and acceptability of long-term coenzyme Q10 use by determining its effects on people with Huntington's disease.

Detailed description

Huntington's disease (HD) is a slowly progressive disorder that devastates the lives of those affected and their families. There are no treatments that slow the progression of HD, only mildly effective symptomatic therapies are available. The purpose of this trial is to find out if coenzyme Q10 (CoQ) is effective in slowing the worsening symptoms of HD. In this study, researchers also will learn about the safety and acceptability of long-term CoQ use by determining its effects on people with HD. Participants in this trial will be randomly chosen to one of two groups. Group 1 will receive CoQ (2400 mg/day), and group 2 will receive a placebo (an inactive substance). Researchers will compare the change in total functional capacity (TFC)-a measure of functional disability-in the two groups. The TFC is a valid and reliable measure of disease progression and is particularly responsive to change in the early and mid-stages of HD. Researchers will also compare the changes in other components of the Unified Huntington's Disease Rating Scale '99 (UHDRS) including: the total motor score, total behavioral frequency score, total behavior frequency X severity score, verbal fluency test, symbol digit modalities test, Stroop, interference test, functional checklist, and independence scale scores. The groups will also be compared with respect to tolerability, adverse events, vital signs, and laboratory test results as measures of safety.

Interventions

DRUGcoenzyme Q10

4 - 300 mg CoQ chewable wafers taken orally twice a day

OTHERplacebo

an inactive substance

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

16 Years to No maximum

Healthy volunteers

Inclusion criteria

To be eligible for enrollment into this study, subjects must meet the following eligibility criteria within 28 days prior to randomization: * Subjects must have clinical features of HD and a confirmed family history of HD, OR a CAG repeat expansion ≥ 36. * TFC \> 9. * Must be ambulatory and not require skilled nursing care. * Age ≥ 16 years. * Women must not be able to become pregnant (e.g., post menopausal, surgically sterile or using adequate birth control methods for the duration of the study). * If psychotropic medications are taken (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants), they must be at a stable dosage for four weeks prior to randomization and should be maintained at a constant dosage throughout the study, as possible. (Note: stable dosing of tetrabenazine is allowable.) Any changes to these medications mandated by clinical conditions will be systematically recorded and the subject will be permitted to remain in the trial. * Able to give informed consent and comply with trial procedures * Able to take oral medication. * May be required to identify an informant or caregiver who will be willing and able to supervise the daily dosing of study medications and to maintain control of study medications in the home. * A designated individual will be identified by the subject to participate in the ongoing consent process should the subject's cognitive capacity to consent become compromised during participation in the study.

Exclusion criteria

* History or known sensitivity of intolerability to CoQ. * Exposure to any investigational drug within 30 days of the Baseline visit. * Clinical evidence of unstable medical illness in the investigator's judgment. * Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression or suicidal ideation within 90 days of the Baseline visit. * Substance (alcohol or drug) abuse within one year of the Baseline visit. * Women who are pregnant or breastfeeding. * Use of supplemental coenzyme Q10 within 30 days prior to the Baseline visit * Clinically serious abnormalities in the screening laboratory studies (Screening creatinine greater than 2.0, alanine aminotransferase (ALT) or total bilirubin greater than 3 times the upper limit of normal, absolute neutrophil count of ≤1000/ul, platelet concentration of \<100,000/ul, hematocrit level of \<33 for female or \<35 for male, or coagulation tests \> 1.5 time upper limit of normal). * Known allergy to FD&C yellow #5 or any other ingredient in the study drug (active and placebo)

Design outcomes

Primary

Measure	Time frame	Description
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))	5 years	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).

Secondary

Measure	Time frame	Description
Change in Functional Checklist Score From Baseline to Month 60	Baseline and Month 60	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.
Change in Independence Scale Score From Baseline to Month 60	Baseline and Month 60	The independence scale assesses independence on a 0 to 100 scale with higher scores indicating better functioning.
Change in Total Motor Score From Baseline to Month 60	Baseline and Month 60	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.
Change in Behavioral Frequency Score From Baseline to Month 60	Baseline and Month 60	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.
Change in Behavioral Frequency x Severity Score From Baseline to Month 60	Baseline and Month 60	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.
Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60	Baseline and Month 60	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.
Change in Total Functional Capacity (TFC) Score From Baseline to Month 60	Baseline and Month 60	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).
Change in Stroop Interference Test - Color Naming From Baseline to Month 60	Baseline and Month 60	Stroop Interference Test - color naming score is the total number of correct colors identified in 45 seconds and reflects processing speed.
Change in Stroop Interference Test - Word Reading From Baseline to Month 60	Baseline and Month 60	Stroop Interference Test - word reading score is the total number of correct words read in 45 seconds and reflects processing speed.
Change in Stroop Interference Test - Interference From Baseline to Month 60	Baseline and Month 60	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 to a Two-Point Decline in TFC Score or Death	5 years	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 to a Three-Point Decline in TFC Score or Death	5 years	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).
Number Completing Study at Assigned Dosage Level	5 years	—
Change in Verbal Fluency Test From Baseline to Month 60	Baseline and Month 60	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.

Countries

Australia, Canada, United States

Participant flow

Participants by arm

Arm	Count
A - Coenzyme Q10 2400 mg/Day Randomized to active treatment (coenzyme Q10 2400 mg/day) coenzyme Q10: 4 - 300 mg CoQ chewable wafers taken orally twice a day	303
B - Placebo Randomized to placebo placebo: an inactive substance	306
Total	609

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	5	3
Overall Study	Death	22	13
Overall Study	Institutionalized	1	2
Overall Study	Lost to Follow-up	28	14
Overall Study	Physician Decision	5	5
Overall Study	Withdrawal by Subject	18	29

Baseline characteristics

Characteristic	A - Coenzyme Q10 2400 mg/Day	B - Placebo	Total
Age, Continuous	50.5 years STANDARD_DEVIATION 11.9	50.7 years STANDARD_DEVIATION 11.6	50.6 years STANDARD_DEVIATION 11.7
Sex: Female, Male Female	149 Participants	164 Participants	313 Participants
Sex: Female, Male Male	154 Participants	142 Participants	296 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	276 / 303	280 / 306
serious Total, serious adverse events	76 / 303	83 / 306

Outcome results

Primary

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))

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

Arm	Measure	Value (MEAN)	Dispersion
A - Coenzyme Q10 2400 mg/Day	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))	303.3 rank	Standard Deviation 173.1
B - Placebo	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))	306.7 rank	Standard Deviation 179

Comparison: 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.95% CI: [0.454, 0.534]

Secondary

Change in Behavioral Frequency Score From Baseline to Month 60

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.