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

This study has been terminated.
(Futility analysis failed to showed likelihoo of benefit of CoQ 2400 mg/day.)
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Rochester
Information provided by (Responsible Party):
Merit E. Cudkowicz, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00608881
First received: February 4, 2008
Last updated: February 29, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Huntington's Disease
Drug: coenzyme Q10
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Coenzyme Q10 in Huntington's Disease (HD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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)) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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:
  • Change in Total Functional Capacity (TFC) Score From Baseline to Month 60 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 Functional Checklist Score From Baseline to Month 60 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Month 60 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 609
Study Start Date: March 2008
Study Completion Date: May 2015
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A - coenzyme Q10 2400 mg/day
Randomized to active treatment (coenzyme Q10 2400 mg/day)
Drug: coenzyme Q10
4 - 300 mg CoQ chewable wafers taken orally twice a day
Other Name: CoQ
Placebo Comparator: B - Placebo
Randomized to placebo
Other: placebo
an inactive substance

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.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608881

  Show 49 Study Locations
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Neurological Disorders and Stroke (NINDS)
University of Rochester
Investigators
Principal Investigator: Merit Cudkowicz, MD MSc Massachusetts General Hospital
Principal Investigator: Michael McDermott, PhD University of Rochester, Biostatistics
Principal Investigator: Karl Kieburtz, MD MPH Director, Clinical Trials Coordination Center, University of Rochester
  More Information

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.
Bruyn G. Huntington's chorea: Historical clinical and laboratory synopsis. In: Vinken P, Bruyn G, eds. Handbook of Clinical Neurology. Amsterdam, 1968: 298-378.
Greenamyre J, Shoulson I. Huntington's Disease. In: Calne D, ed. Neurodegenerative Diseases. Philadelphia: WB Saunders, 1994: 685-704.
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.
Yamagami T, Okishio T, Toyama S, Kishi T. Correlation of serum coenzyme Q10 level and leukocute complex II activity in nformal and cardiovascular patients. In: Folkers K, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1981: 79-89.
Dubois B, Brand M, Garcia de Yebenes J, et al. European-Huntington's-disease-Initiative (EHDI)-Trial: Objectives, design, and description of the study population at the end of inclusion. Mov Dis 2002;17:S319.
Bogentoft C, Edelund P, Olsson B, Widlund L, Westensen K. Biopharmaceutical aspects of intraveneous and oral administration of coenzyme Q10. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q.: Elsevier Science Publishers, 1991: 215-224.
Lucker P, Wetselsberg N, Hennings G, Rehn D. Pharmacokinetics of coenzyme ubidecarenone in healthy volunteers. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1984: 143-151.
Micromedex. Ubidecarenone drug monograph. Engelwood 1995 May; Update 1998 Mar.
Weber C. Dietary intake and absorption of coenzyme Q. In: Kagan V, Quinn P, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton: CRC Press, 2001:209-215.
Saito Y, Kubo H, Bujo H, Yamamoto Y. The changes in plasma coenzyme Q10 level during the statin therapy for hypercholesterolemic patients. In: Second Conference of the International Coenzyme Q10 Association.; 2000, 2000: 59.

Responsible Party: Merit E. Cudkowicz, MD, Julieanne Dorn Professor of Neurology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00608881     History of Changes
Other Study ID Numbers: 2CARE 01.00  5U01NS052592  5R01NS052619 
Study First Received: February 4, 2008
Results First Received: December 7, 2015
Last Updated: February 29, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada

Keywords provided by Massachusetts General Hospital:
Huntington's disease
Huntington disease
HD
coenzyme Q10
CoQ

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Coenzyme Q10
Ubiquinone
Micronutrients
Growth Substances
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on September 27, 2016