Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00951834
Recruitment Status : Completed
First Posted : August 4, 2009
Last Update Posted : April 15, 2020
Sponsor:
Information provided by (Responsible Party):
Friedemann Paul, Charite University, Berlin, Germany

Tracking Information
First Submitted Date  ICMJE August 3, 2009
First Posted Date  ICMJE August 4, 2009
Last Update Posted Date April 15, 2020
Study Start Date  ICMJE October 2009
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2009)
ADAS-COG (Score 0-70) (Baseline to treatment) [ Time Frame: 18 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2009)
  • Safety and tolerability of the verum [ Time Frame: 18 months ]
  • MMSE (Score 0-30) after 18 months compared to baseline [ Time Frame: 18 months ]
  • Time to hospitalisation and Time to death related to AD [ Time Frame: 18 months ]
  • Brain atrophy assessed by brain MRI [ Time Frame: 18 months ]
  • Baseline-ADAS-COG and Baseline-MMSE as covariates [ Time Frame: 18 months ]
  • CIBIC+ and WHO-QOL-Bref [ Time Frame: 18 months ]
  • Trail Making Test and MVGT [ Time Frame: 18 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sunphenon EGCg (Epigallocatechin-Gallate) in the Early Stage of Alzheimer´s Disease
Official Title  ICMJE Sunphenon EGCg (Epigallocatechin-Gallate) in the Early Stage of Alzheimer´s Disease
Brief Summary

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.

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Epigallocatechin-Gallate
  • Placebo Comparator: Placebo
    add-on to Donepezil.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 4, 2015)
21
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2009)
50
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00951834
Other Study ID Numbers  ICMJE SUN-AK
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Friedemann Paul, Charite University, Berlin, Germany
Study Sponsor  ICMJE Charite University, Berlin, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Friedemann Paul, MD Charite University Medicine Berlin, NeuroCure
PRS Account Charite University, Berlin, Germany
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP