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

Phase 2
Completed
Conditions
Huntington Disease
Interventions
Drug: (2)-epigallocatechin-3-gallate (EGCG)
Drug: Placebo
Registration Number
NCT01357681
Lead Sponsor
Charite University, Berlin, Germany
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
54
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
(2)-epigallocatechin-3-gallate (EGCG)(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.
PlaceboPlaceboPlacebo
Primary Outcome Measures
NameTimeMethod
Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baselineMonth 0, Month 12
Secondary Outcome Measures
NameTimeMethod
Clinical Global Impression (CGI)Month 0, Month 12
UHDRS Motor ScoreMonth 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 AlertnessMonth 0, Month 12
Global Cognition: Mini Mental State ExaminationScreening, Month 12, Month 13
Quantitative evaluation of motor functions: QmotorMonth 0, Month 12
Brain atrophy: assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)Month 0, Month 12
UHDRS Behavioural ScoreMonth 0, Month 12
UHDRS Functional AssessmentMonth 0, Month 12
Pharmacokinetics and tolerability of EGCGMonth 1 - Month 12

assessment of side effects and determination of blood and cerebrospinal fluid (CSF) levels of EGCG

Determination of huntingtin expression levelsScreening - Month 13

Quantification of huntingtin in blood and CSF (optional)

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

Trial Locations

Locations (3)

Universitätsklinikum Ulm, Klinik für Neurologie

🇩🇪

Ulm, Germany

Neurologische Klinik der Ruhr-Universität Bochum

🇩🇪

Bochum, Germany

Department of Neuropsychiatry

🇩🇪

Berlin, Germany

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