Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease The ETON-Study - A Randomized, Double-blind, Stratified, Placebo-controlled Prospective Investigator Initiated Multicenter Trial -
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 3
- 主要终点
- Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baseline
研究概览
简要总结
Huntington's disease (HD) is an inherited autosomal dominant, progressive neurodegenerative disease. Clinically, HD is characterized by a triad of movement disorders, cognitive impairments and psychiatric disturbances. These symptoms represent a tremendous burden for patients and caregivers. HD is a fatal disorder with neither cure, nor evidence-based standard therapy available.
The green tea polyphenon (2)-epigallocatechin-3-gallate (EGCG) was shown to have beneficial effects in cell and animal models of HD. The aim of this study is to evaluate the efficacy and tolerability of EGCG in HD.
The investigators hypothesize that Sunphenon EGCG administered at a maximal daily dose of 1200 mg compared to placebo during a period of 12 months improves cognition in patients with HD. As primary outcome measure, the change of cognitive functions (as measured by the Unified Huntington's Disease Rating Scale (UHDRS)-Cognition composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to Baseline was defined.
The investigators further expect a positive influence of EGCG on other clinical manifestations of HD, measurable effects of EGCG on HD biomarkers and good safety and tolerability of EGCG in HD patients.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chorea Huntington (CAG repeats >39)
- •UHDRS TFC >5
- •≥18 years of age
- •Readiness and ability to take oral medication
- •Normal liver function laboratory test
- •Stable concomitant medication regimen > 4 weeks prior to Baseline
- •Motivation for women with childbearing potential to use highly efficient contraception
排除标准
- •Clinically relevant abnormal findings in the ECG, vital signs, physical examination or laboratory values at Screening,
- •Long-term treatment with potentially hepatoxic medication
- •Any unstable medical condition
- •BDI Depression score > 9 AND clinical diagnosis of depression
- •Suicidal tendencies
- •Cognitive dysfunction defined as a score < 23 in the Mini-Mental State Examination (MMSE) at Screening
- •Liver or renal disease
- •Schizophreniform psychosis within the last 6 months before baseline
- •Consumption of more than two cups of black tea per day, consumption of green tea, consumption of > 500 ml /day of grapefruit juice
- •Participation in other Arzneimittelgesetz (AMG) or Medizinproduktegesetz (MPG) studies (three months before and during participation)
- •Pregnancy/ lactation
研究组 & 干预措施
(2)-epigallocatechin-3-gallate (EGCG)
Month 01:400 mg /day (200-0-200) p.o. Month 02:800 mg /day (400-0-400) p.o. Month 03 -12: 1200 mg /day (600-0-600) p.o.
干预措施: (2)-epigallocatechin-3-gallate (EGCG) (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baseline
时间窗: Month 0, Month 12
次要结局
- Clinical Global Impression (CGI)(Month 0, Month 12)
- UHDRS Motor Score(Month 0, Month 12)
- Subjective Well-Being: Satisfaction With Life Scale (SWLS)(Month 0, Month 12, Month 13)
- UHDRS Total Functional Capacity (TFC)(Screening, Month 12)
- Health-related Quality of Life: Short Form (36) Health Survey (SF-36)(Month 0, Month 12)
- Tonic and phasic Alertness(Month 0, Month 12)
- Global Cognition: Mini Mental State Examination(Screening, Month 12, Month 13)
- Quantitative evaluation of motor functions: Qmotor(Month 0, Month 12)
- Brain atrophy: assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)(Month 0, Month 12)
- UHDRS Behavioural Score(Month 0, Month 12)
- UHDRS Functional Assessment(Month 0, Month 12)
- Pharmacokinetics and tolerability of EGCG(Month 1 - Month 12)
- Determination of huntingtin expression levels(Screening - Month 13)
- Depression: Beck Depression Inventory (BDI)(Screening, Month 1, Month 2, Month 3, Month 6, Month 9, Month12, Month 13)
- Affective Processing: Positive and Negative Affect Schedule (PANAS)(Month 0, Month 12, Month 13)
研究者
Josef Priller
Prof. Dr. med; Director, Department of Neuropsychiatry
Charite University, Berlin, Germany