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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Josef Priller, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01357681
First received: May 19, 2011
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Huntington Disease
Drug: (2)-epigallocatechin-3-gallate (EGCG)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 -

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Change of cognitive functions (UHDRS-Cognition: composite score of Stroop test, Verbal fluency & Symbol Digit Modalities Test) after 12 months in comparison to baseline [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • UHDRS Motor Score [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • UHDRS Behavioural Score [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • UHDRS Functional Assessment [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • UHDRS Total Functional Capacity (TFC) [ Time Frame: Screening, Month 12 ] [ Designated as safety issue: No ]
  • Clinical Global Impression (CGI) [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • Depression: Beck Depression Inventory (BDI) [ Time Frame: Screening, Month 1, Month 2, Month 3, Month 6, Month 9, Month12, Month 13 ] [ Designated as safety issue: No ]
  • Health-related Quality of Life: Short Form (36) Health Survey (SF-36) [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • Subjective Well-Being: Satisfaction With Life Scale (SWLS) [ Time Frame: Month 0, Month 12, Month 13 ] [ Designated as safety issue: No ]
  • Affective Processing: Positive and Negative Affect Schedule (PANAS) [ Time Frame: Month 0, Month 12, Month 13 ] [ Designated as safety issue: No ]
  • Tonic and phasic Alertness [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • Global Cognition: Mini Mental State Examination [ Time Frame: Screening, Month 12, Month 13 ] [ Designated as safety issue: No ]
  • Quantitative evaluation of motor functions: Qmotor [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • Brain atrophy: assessed by magnetic resonance imaging (MRI)-voxel-based morphometry (VBM) [ Time Frame: Month 0, Month 12 ] [ Designated as safety issue: No ]
  • Pharmacokinetics and tolerability of EGCG [ Time Frame: Month 1 - Month 12 ] [ Designated as safety issue: Yes ]
    assessment of side effects and determination of blood and cerebrospinal fluid (CSF) levels of EGCG

  • Determination of huntingtin expression levels [ Time Frame: Screening - Month 13 ] [ Designated as safety issue: No ]
    Quantification of huntingtin in blood and CSF (optional)


Enrollment: 54
Study Start Date: September 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01357681

Locations
Germany
Department of Neuropsychiatry
Berlin, Germany, 10117
Neurologische Klinik der Ruhr-Universität Bochum
Bochum, Germany, 44791
Universitätsklinikum Ulm, Klinik für Neurologie
Ulm, Germany, 89081
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Josef Priller, MD Department of Neuropsychiatry, Charité Universitätsmedizin Berlin, Germany
  More Information

No publications provided

Responsible Party: Josef Priller, Prof. Dr. med; Director, Department of Neuropsychiatry, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01357681     History of Changes
Other Study ID Numbers: 2010-023941-31
Study First Received: May 19, 2011
Last Updated: September 8, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
Huntington Disease
Cognition
Motor
Behaviour
Functional Capacity
Quality of Life
Biomarker
MRI
Huntingtin
EGCG

Additional relevant MeSH terms:
Brain Diseases
Huntington Disease
Basal Ganglia Diseases
Central Nervous System Diseases
Chorea
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Dyskinesias
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Mental Disorders
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Epigallocatechin gallate
Anticarcinogenic Agents
Antimutagenic Agents
Antineoplastic Agents
Antioxidants
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014