Coenzyme Q10 in Huntington's Disease (HD)
- Registration Number
- NCT00608881
- Lead Sponsor
- Massachusetts General Hospital
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 609
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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description B - Placebo placebo Randomized to placebo A - coenzyme Q10 2400 mg/day coenzyme Q10 Randomized to active treatment (coenzyme Q10 2400 mg/day)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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.
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 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 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.
Trial Locations
- Locations (49)
Emory University, Wesley Woods Center, 1841 Clifton Road NE Room 314
🇺🇸Atlanta, Georgia, United States
Idaho Elks Rehabilitation Hospital, 600 North Robbins Road
🇺🇸Boise, Idaho, United States
University of Maryland School of Medicine, 22 South Greene Street, N4 W49-B
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University, 600 North Wolfe Street, Meyer 2-181
🇺🇸Baltimore, Maryland, United States
Albany Medical College, Parkinson'S Disease & Movement Disorders Ctr
🇺🇸Albany, New York, United States
UN oF TEXAS SOUTHWESTERN MED CENTER DALLAS, 5323 HARRY HINES BOULEVARD H1.108
🇺🇸Dallas, Texas, United States
NORTH YORK GENERAL HOSPITAL (2), 4001 Leslie Street
🇨🇦Toronto, Ontario, Canada
North York General Hospital, 4001 Leslie Street
🇨🇦Toronto, Ontario, Canada
Struthers Parkinson'S Center, 6701 Country Club Drive
🇺🇸Golden Valley, Minnesota, United States
Nj Neuroscience Institute, Jfk Medical Center, 65 James Street
🇺🇸Edison, New Jersey, United States
Massachusetts General Hospital, 149 13Th Street Suite 2241
🇺🇸Charlestown, Massachusetts, United States
OHIO STATE UNIVERSITY , 2006 Kenny Road
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Kaufmann Medical Building, 3471 Fifth Avunue, Suite 811
🇺🇸Pittsburgh, Pennsylvania, United States
University of Iowa Hospital and Clinics, 200 Hawkins Road, Room W263 General Hospital
🇺🇸Iowa City, Iowa, United States
London Health Sciences Centre, University Hospital, 339 Windermere Road
🇨🇦London, Ontario, Canada
Washington University School of Medicine, Box 8111, 660 South Euclid
🇺🇸St Louis, Missouri, United States
University of California Irvine, Department of Neurology, 100 Irvine Hall
🇺🇸Irvine, California, United States
ST. LUKE'S HOSPITAL, 240 Centronia Road
🇺🇸Allentown, Pennsylvania, United States
Centre For Movement Disorders, 2780 Bur Oak Avenue
🇨🇦Markham, Ontario, Canada
BUTLER HOSPTIAL MOVEMENT DISORDER PROGRAM, 345 Blackstone Boulevard
🇺🇸Providence, Rhode Island, United States
Columbia University, Sergievsky Center P&S Box 16, 630 West 168Th Street
🇺🇸New York, New York, United States
North Shore-Lij Health System, 350 Community Drive Room 110, Research Institute
🇺🇸Manhasset, New York, United States
Wake Forest University, Baptist Med Center, Department of Neurology, Medical Center Boulevard
🇺🇸Winston Salem, North Carolina, United States
UNIVERSITY OF MIAMI, 1150 NW 14th STREET, #401
🇺🇸Miami, Florida, United States
Indiana University School of Medicine, Outpatient Clinical Research Facility, 535 Barnhill Drive Room #150
🇺🇸Indianapolis, Indiana, United States
Boston University School of Medicine, Department of Neurology, 715 Albany Street C329
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine, 6550 Fannin Suite 1801
🇺🇸Houston, Texas, United States
University of Las Vegas School of Medicine, 1707 W. Charleston Blvd, Suite 220
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati/Cincinnati Children'S Hospital, 222 Piedmont Avenue, Suite 3200
🇺🇸Cincinnati, Ohio, United States
University of Alberta, Glenrose Rehab Hosp, Movement Disorder Clinic , Rm 0601 Gleneast 10230 - 111 Avenue
🇨🇦Edmonton, Alberta, Canada
Department of Medical Genetics, Ubc Hospital, Room S179-2211 Westbrook Mall
🇨🇦Vancouver, British Columbia, Canada
WASHINGTON REGIONAL MEDICAL CENTER, 3215 N. North Hills Blvd
🇺🇸Fayetteville, Arkansas, United States
Mayo Clinic Arizona, 13400 East Shea Boulevard, Csu-Cp21B
🇺🇸Scottsdale, Arizona, United States
Colorado Neurological Institute, Movement Disorders Center, 701 East Hampden Avenue Suite 510
🇺🇸Littleton, Colorado, United States
Rush University Medical Center, Department of Neurological Sciences, 1725 West Harrison Suite 755
🇺🇸Chicago, Illinois, United States
University of Kansas Medical Center, Department of Neurology, 3599 Rainbow Blvd Mail Stop 2012
🇺🇸Kansas City, Kansas, United States
Hereditary Neurological Disease Centre (Hndc),3223 N. Webb, Suite 4
🇺🇸Wichita, Kansas, United States
Cooper University Hospital
🇺🇸Camden, New Jersey, United States
University of Rochester, Department of Neurology, 919 Westfall Road Building C Suite 220
🇺🇸Rochester, New York, United States
University of Pennsylvania, Pennsylvania Hospital Department of Neurology , 330 South 9Th Street
🇺🇸Philadelphia, Pennsylvania, United States
The University of Tennesee Health Science Cen, 855 Monroe Avenue, Department of Neurology, Room 415 Link Bldg
🇺🇸Memphis, Tennessee, United States
Westmead Hospital, Department of Neurology Level 1, Po Box 533
🇦🇺Wentworthville, New South Wales, Australia
University of Calgary, Heritage Medical Research Clinic, Trw Bldg 5 Floor, 3280 Hospital Dri. NW
🇨🇦Calgary, Alberta, Canada
University of Alabama At Birmingham, Pediatric Neurology Childrens, Harbor Bldg Suite 314, 1600 7Th Avenue South
🇺🇸Birmingham, Alabama, United States
University of South Florida, College of Medicine Dept of Neurology, 12901 Bruce B Downs Blvd Mdc-55
🇺🇸Tampa, Florida, United States
Duke University, 932 Morreene Road #213
🇺🇸Durham, North Carolina, United States
University of California Davis, Medical Center Dept of Neurology, Acc Building Suite 3700, 4860 Y Street
🇺🇸Sacramento, California, United States
University of Florida Center for Movement Disorders and Neurorestoration, 3450 Hull Road, 4th Floor
🇺🇸Gainesville, Florida, United States
University of Michigan, 1500 E Medical Center Drive, B1 H202 Nuclear Medicine
🇺🇸Ann Arbor, Michigan, United States