Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease (ETON-Study)

Study Overview
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Brief Summary
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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.

Official Title
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Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease The ETON-Study - A Randomized, Double-blind, Stratified, Placebo-controlled Prospective Investigator Initiated Multicenter Trial -

Conditions
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Huntington Disease

Intervention / Treatment
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* Drug: (2)-epigallocatechin-3-gallate (EGCG)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: (2)-epigallocatechin-3-gallate (EGCG)<br>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. | Drug: (2)-epigallocatechin-3-gallate (EGCG)<br>* Month 01:400 mg /day (200-0-200) Month 02:800 mg /day (400-0-400) Month 03 -12: 1200 mg /day (600-0-600)<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baseline |  | Month 0, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UHDRS Motor Score |  | Month 0, Month 12 | 
| UHDRS Behavioural Score |  | Month 0, Month 12 | 
| UHDRS Functional Assessment |  | Month 0, Month 12 | 
| UHDRS Total Functional Capacity (TFC) |  | Screening, Month 12 | 
| Clinical Global Impression (CGI) |  | Month 0, Month 12 | 
| Depression: Beck Depression Inventory (BDI) |  | Screening, Month 1, Month 2, Month 3, Month 6, Month 9, Month12, Month 13 | 
| Health-related Quality of Life: Short Form (36) Health Survey (SF-36) |  | Month 0, Month 12 | 
| Subjective Well-Being: Satisfaction With Life Scale (SWLS) |  | Month 0, Month 12, Month 13 | 
| Affective Processing: Positive and Negative Affect Schedule (PANAS) |  | Month 0, Month 12, Month 13 | 
| 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 | 
| Pharmacokinetics and tolerability of EGCG | assessment of side effects and determination of blood and cerebrospinal fluid (CSF) levels of EGCG | Month 1 - Month 12 | 
| Determination of huntingtin expression levels | Quantification of huntingtin in blood and CSF (optional) | Screening - Month 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Motor, Huntington Disease, Cognition, Behaviour, Functional Capacity, Quality of Life, Biomarker, MRI, Huntingtin, EGCG