A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
研究概览
简要总结
The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.
详细描述
MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes), a progressive and often devastating multisystem disorder, is most commonly associated with mitochondrial Deoxyribonucleic acid (mtDNA) point mutation at nucleotide 3243. Seizures, cognitive deterioration, and neurobehavioral abnormalities are frequent features of this disease which typically shortens life expectancy. Idebenone, an ATP production modulator and antioxidant, improves neurological function in Friedreich's ataxia, a disease also associated with mitochondrial dysfunction.
Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group.
The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). Patients will receive idebenone (900 mg/day or 2250 mg/day) or matching placebo for one month. The primary outcome measure is cerebral lactate levels measured by Magnetic Resonance Spectroscopy (MRS), a biomarker associated with disease worsening. This study will help the investigators to determine if there is sufficient signal to proceed to efficacy studies. Also it will provide additional information on the safety and tolerability of two different doses of idebenone in MELAS.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss)
- •Cerebral lactate level equal to or greater than 5.0 i.u. at baseline
- •Patients at least 8 and < 65 years of age at baseline
- •Patients with a body weight > 37 kg/82 lbs at baseline
- •Stable co-medication/vitamins/supplements within 1 month prior to baseline
- •Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication
- •Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)
排除标准
- •Contraindication to MRS (e.g. metal implant, claustrophobia)
- •Stroke like event within 2 months prior to baseline
- •Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline
- •Inadequate contraception use
- •Pregnancy and/or breast-feeding
- •Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine
- •Current abuse of drugs or alcohol
- •Participation in a trial of another investigational drug within the last month
- •Other factor that, in the investigator's opinion, excludes the patient from entering the study
研究组 & 干预措施
Idebenone 900 mg/day
Idebenone 900 mg/day
干预措施: Idebenone (Drug)
Idebenone 2250 mg/day
Idebenone 2250 mg/day
干预措施: Idebenone (Drug)
placebo
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
时间窗: Up to 4 weeks from baseline
To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)
次要结局
- Mean Change in Venous Lactate Concentration(Up to 4 weeks from baseline)
- Mean Change in Score on the Fatigue Severity Scale (FSS)(Baseline and Week 4)
研究者
Michio Hirano
Professor of Neurology
Columbia University