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

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

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.

Study Overview

• Status: Completed
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Placebo; Drug: (2)-epigallocatechin-3-gallate (EGCG)

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Department of Neuropsychiatry
  • Bochum, Germany, 44791
    • Neurologische Klinik der Ruhr-Universität Bochum
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm, Klinik für Neurologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Experimental: (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.	Drug: (2)-epigallocatechin-3-gallate (EGCG); 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Josef Priller, MD, Department of Neuropsychiatry, Charité Universitätsmedizin Berlin, Germany

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Estimate): June 16, 2015
• Last Update Submitted That Met QC Criteria: June 15, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: MRI; Biomarker; Quality of Life; Cognition; Huntington Disease; Motor; Functional Capacity; Behaviour; EGCG; Huntingtin
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: 2010-023941-31