Coenzyme Q10 in Huntington's Disease (HD)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 609
- 试验地点
- 49
- 主要终点
- 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))
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •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.
排除标准
- •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)
研究组 & 干预措施
A - coenzyme Q10 2400 mg/day
Randomized to active treatment (coenzyme Q10 2400 mg/day)
干预措施: coenzyme Q10 (Drug)
B - Placebo
Randomized to placebo
干预措施: placebo (Other)
结局指标
主要结局
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))
时间窗: 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).
次要结局
- Change in Functional Checklist Score From Baseline to Month 60(Baseline and Month 60)
- Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60(Baseline and Month 60)
- Change in Verbal Fluency Test From Baseline to Month 60(Baseline and Month 60)
- Change in Stroop Interference Test - Color Naming From Baseline to Month 60(Baseline and Month 60)
- Change in Stroop Interference Test - Word Reading From Baseline to Month 60(Baseline and Month 60)
- Change in Stroop Interference Test - Interference From Baseline to Month 60(Baseline and Month 60)
- Time to a Two-Point Decline in TFC Score or Death(5 years)
- Time to a Three-Point Decline in TFC Score or Death(5 years)
- 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)
- Change in Independence Scale Score From Baseline to Month 60(Baseline and Month 60)
- Change in Total Motor Score From Baseline to Month 60(Baseline and Month 60)
- Change in Behavioral Frequency Score From Baseline to Month 60(Baseline and Month 60)
- Change in Behavioral Frequency x Severity Score From Baseline to Month 60(Baseline and Month 60)
研究者
Merit E. Cudkowicz, MD
Julieanne Dorn Professor of Neurology
Massachusetts General Hospital