Clinical trial NCT01357681: Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease (ETON-Study)
Official title: Effects of EGCG (Epigallocatechin Gallate) in Huntington's Disease The ETON-Study - A Randomized, Double-blind, Stratified, Placebo-controlled Prospective Investigator Initiated Multicenter Trial -
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Huntington Disease
Keywords: Huntington Disease
Cognition
Motor
Behaviour
Functional Capacity
Quality of Life
Biomarker
MRI
Huntingtin
EGCG
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2011-05-23
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baseline
timeFrame: Month 0, Month 12
Secondary outcomes:
measure: UHDRS Motor Score
timeFrame: Month 0, Month 12
measure: UHDRS Behavioural Score
timeFrame: Month 0, Month 12
measure: UHDRS Functional Assessment
timeFrame: Month 0, Month 12
measure: UHDRS Total Functional Capacity (TFC)
timeFrame: Screening, Month 12
measure: Clinical Global Impression (CGI)
timeFrame: Month 0, Month 12
measure: Depression: Beck Depression Inventory (BDI)
timeFrame: Screening, Month 1, Month 2, Month 3, Month 6, Month 9, Month12, Month 13
measure: Health-related Quality of Life: Short Form (36) Health Survey (SF-36)
timeFrame: Month 0, Month 12
measure: Subjective Well-Being: Satisfaction With Life Scale (SWLS)
timeFrame: Month 0, Month 12, Month 13
measure: Affective Processing: Positive and Negative Affect Schedule (PANAS)
timeFrame: Month 0, Month 12, Month 13
measure: Tonic and phasic Alertness
timeFrame: Month 0, Month 12
measure: Global Cognition: Mini Mental State Examination
timeFrame: Screening, Month 12, Month 13
measure: Quantitative evaluation of motor functions: Qmotor
timeFrame: Month 0, Month 12
measure: Brain atrophy: assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM)
timeFrame: Month 0, Month 12
measure: Pharmacokinetics and tolerability of EGCG
timeFrame: Month 1 - Month 12
measure: Determination of huntingtin expression levels
timeFrame: Screening - Month 13
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Department of Neuropsychiatry
city: Bochum
country: Germany
facility: Neurologische Klinik der Ruhr-Universität Bochum
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Klinik für Neurologie
Study officials:
affiliation: Department of Neuropsychiatry, Charité Universitätsmedizin Berlin, Germany
name: Josef Priller, MD
role: PRINCIPAL_INVESTIGATOR
References: