Sunphenon EGCg (Epigallocatechin-Gallate) in the Early Stage of Alzheimer´s Disease (SUN-AK)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Charite University, Berlin, Germany
Sponsor:
Information provided by (Responsible Party):
Friedemann Paul, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT00951834
First received: August 3, 2009
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

EGCG has shown a neuroprotective effect in cell-experimental and animal studies. The neuroprotective mechanism of EGCG probably bases - besides the known antioxidant effect - amongst others on the modulation of several signal transduction pathways, the influence on the expression of genes which regulate cell survival resp. programmed cell death, as well as the modulation of the mitochondrial function. In different Alzheimer models EGCG seems to cause an induction of alpha-secretase and the endothelin-converting-enzyme, as well as to prevent the aggregation of beta-amyloid to toxic oligomers through the direct binding to the unfolded peptide.

The investigators therefore expect EGCG to have a positive influence on the course of the Alzheimer´s Disease.


Condition Intervention Phase
Alzheimer's Disease
Drug: Epigallocatechin-Gallate
Drug: Placebo
Phase 2
Phase 3

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: Sunphenon EGCg (Epigallocatechin-Gallate) in the Early Stage of Alzheimer´s Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • ADAS-COG (Score 0-70) (Baseline to treatment) [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of the verum [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • MMSE (Score 0-30) after 18 months compared to baseline [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Time to hospitalisation and Time to death related to AD [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Brain atrophy assessed by brain MRI [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Baseline-ADAS-COG and Baseline-MMSE as covariates [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • CIBIC+ and WHO-QOL-Bref [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Trail Making Test and MVGT [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: October 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epigallocatechin-Gallate
  • Months 1-3: 200 mg EGCG/die (200-0-0 mg)
  • Months 4-6: 400 mg EGCG/die (200-0-200 mg)
  • Months 7-9: 600 mg EGCG/die (400-0-200 mg)
  • Months 10-18: 800 mg EGCG/die (400-0-400 mg)

add-on to Donepezil.

Drug: Epigallocatechin-Gallate

Epigallocatechin-Gallate (EGCG) - Sunphenon EGCg:

  • Months 1-3: 200 mg EGCG/die (200-0-0 mg)
  • Months 4-6: 400 mg EGCG/die (200-0-200 mg)
  • Months 7-9: 600 mg EGCG/die (400-0-200 mg)
  • Months 10-18: 800 mg EGCG/die (400-0-400 mg)
Other Name: Sunphenon EGCG
Placebo Comparator: Placebo
add-on to Donepezil.
Drug: Placebo
Placebo
Other Name: Placebo

Detailed Description:

Alzheimer's disease (AD) is a progressive dementia characterised by an ongoing loss of memory function and of at least one additional cognitive domain resulting in impairment of daily life functioning. Treatment of diseases such as diabetes mellitus, fractures and cardiovascular diseases is more expensive and complicated in patients with dementia compared to those without. The yearly costs for treatment and care of AD patients in the US are estimated to exceed 100 billion USD. Life expectancy is reported to be about 10 years after establishment of the diagnosis and is significantly reduced compared to non-demented subjects of similar age and socio-economic status.

Age is the most relevant risk factor for AD, followed by genetic factors. Prevalence is less than 1% amongst individuals aged 50-60, but is reported to double every 5 years beyond the age of 60. The prevalence exceeds 30% in the age of 85-90.

The only standard therapy for AD are acetylcholine-esterase inhibitors (AchEI; donepezil, galantamine, rivastigmine). AchEI exhibit a temporary stabilizing mild effect on the progression of AD. Conversion rates from "mild cognitive impairment" to AD do not seem to be beneficially influenced by AchEI. A high percentage of premature study withdrawals owing to adverse events has been observed in AchEI studies published to date. The questionable benefit may further be outweighed by high costs of the AchEI.

Therefore, there is a necessity for the development of more efficacious and less expensive disease-modifying drugs with a better safety and tolerability profile. EGCG is a promising compound which has proven efficacious in AD animal models and which has shown an excellent tolerability in our 18-month clinical trial on Multiple Sclerosis currently being performed at our institution (SuniMS study, NCT00525668).

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • early stage of AD (Diagnosis DSM-IV and NINCDS/ADRDA, Dubois-criteria 2007)
  • age 60-100
  • MMSE 20-26
  • patient lives at home with at least one relative who perform external ratings/assessment
  • co-medication with Donepezil (Aricept®, Pfizer Pharma GmbH) with at least 3 months to maximum 6 months of existing stable medication
  • maximum of 2 cups of black tea/die, no green tea, not more than > 500 ml/die of grapefruit juice

Exclusion Criteria:

  • co-medication with NSAIDs (longterm medication) (ASS is not an exclusion criteria), Gingko- or other natural extracts, other anti-dementiva except of Donepezil
  • familial autosomal-dominant inherited AD
  • instable medical condition
  • other primary psychiatric/neurologic disorders
  • missing informed consent
  • no readiness to save and refer pseudonym personal data
  • hospitalisation due to juridical or legal regulation
  • any condition disturbing or making MRI and other measures impossible
  • clinically relevant GI-disorders at screening and 1 year before
  • clinically relevant lung, infectious, heart or other CNS disorders, clinical or paraclinical suspicion of TBC, history of vascular CNS-disorders at screening and 1 year before
  • clinically relevant liver disorders at screening and 1 year before
  • clinically relevant functional disorders of liver, kidney or bone marrow defined by following lab values at screening:

    • Marrow dysfunction:

      • HB < 8,5 g/dl
      • WBC < 2,5/nl
      • Thrombocytes < 125/nl
    • Kidney dysfunction:

      • Creatinin-Clearance according to Cockcroft-Gault-Formula: Cl < 110ml/min (male) resp. Cl < 95ml/min (female), from the age of 30 decline of 10ml/min per decade
    • Liver dysfunction:

      • ASAT/ALAT > 3.5 x higher than the upper reference value
      • Bilirubin > 2.0 mg/dl
  • known allergy of elements of Sunphenon EGCg or additives of Sunphenon EGCg resp. placebo
  • long-term hepatotoxic medication
  • current intake of cytochrom P450 3A4-inhibitors or -inductors, such as antimycotics of the azol-type or macrolide-antibiotics
  • clinical-anamnestic or paraclinical manifestations suggesting an alcohol or drug abuse
  • participation in any clinical trial < 3 months prior to screening or ongoing
  • any medical, psychiatric or other condition which might constrain the ability of the patient to understand the informed consent, to give consent, to adhere to the protocol or to accomplish the study
  • massive and extended sun exposure
  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: NCT00951834

Contacts
Contact: Friedemann Paul, MD +49 30 450 539 705 friedemann.paul@charite.de
Contact: Jan-Markus Dörr, MD +49 30 450 660 162 jan-markus.doerr@charite.de

Locations
Germany
Charité Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie Completed
Berlin, Germany, 10117
Charite University Medicine Berlin Recruiting
Berlin, Germany, 10117
Contact: Friedemann Paul, MD    +49 30 450 539 705    friedemann.paul@charite.de   
Contact: Jan-Markus Dörr, MD    +49 30 450 660 162    jan-markus.doerr@charite.de   
Principal Investigator: Friedemann Paul, MD         
Klinik für Neurologie Recruiting
Ulm, Germany, 89081
Contact: Christine von Arnim, Prof. Dr. med.    ++49 731 500-63011    christine.arnim@uni-ulm.de   
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Friedemann Paul, MD Charite University Medicine Berlin, NeuroCure
  More Information

Additional Information:
No publications provided

Responsible Party: Friedemann Paul, PI, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT00951834     History of Changes
Other Study ID Numbers: SUN-AK
Study First Received: August 3, 2009
Last Updated: February 19, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
Alzheimer´s Disease
Epigallocatechin-Gallate
Neuroprotection
ADAS-COG
early stage of Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014