Treatment of cardiac amyloid light-chain amyloidosis with the green tea compound epigallocatechin-3-galiate

ISRCTN	ISRCTN68399350
DOI	https://doi.org/10.1186/ISRCTN68399350
EudraCT/CTIS number	2012-004520-38
Secondary identifying numbers	N/A

Submission date: 29/09/2012
Registration date: 05/10/2012
Last edited: 30/11/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Systemic amyloid light-chain amyloidosis is a rare but serious condition where abnormal bone marrow cells produce excessive amounts of abnormal proteins, which form deposits called amyloid in tissues and organs throughout the body. Amyloid deposited in the heart can cause it to become enlarged and impair its ability to pump blood efficiently around the body, which may result in heart failure. Treatment currently involves having chemotherapy to damage the abnormal bone marrow cells and stop the production of the abnormal proteins. Epigallocatechin-3-gallate (EGCG), a chemical found in found in green tea, may be able to reduce the formation of amyloid and break it down. The aim of this study is to find out whether EGCG is able to reduce amyloid deposition in the heart.

Who can participate?
Patients with systemic amyloid light-chain amyloidosis affecting the heart

What does the study involve?
Participants are randomly allocated to take either increasing doses of EGCG capsules or a placebo (dummy drug) for 12 months. Participants come to the center for tests every 3 months. Echocardiography (a heart scan) is performed every 6 months. A heart MRI scan is carried out at the beginning and at the end of treatment.

What are the possible benefits and risks of participating?
EGCG may help to break down amyloid in the heart. There are no known risks of EGCG treatment.

Where is the study run from?
Ruprecht-Karls-University of Heidelberg (Germany)

When is the study starting and how long is it expected to run for?
December 2012 to November 2017

Who is funding the study?
Federal Ministry of Education and Research (Germany)

Who is the main contact?
Dr Stefan Schönland
stefan.schoenland@med.uni-heidelberg.de

Contact information

Dr Stefan Schönland
Scientific

Medical Department V
(Hematology/Amyloidosis Clinic)
Im Neuenheimer Feld 672
Heidelberg
D-69120
Germany

Email	stefan.schoenland@med.uni-heidelberg.de

Study information

Study design	Randomised placebo-controlled double-blind single-centre phase IIb study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	A randomised trial for the Treatment of cardiac AMyloid light-chain amyloidosis with the green tea compound Epigallocatechin-3-gALlate (TAME-AL)
Study acronym	TAME-AL
Study objectives	One year treatment with Epigallocatechin-3-gallate (EGCG) reduces cardiac mass in patients with AL amyloidosis.
Ethics approval(s)	Ethics Committee of The University Heidelberg, 08/04/2013, ref: AFmo-008/2013
Health condition(s) or problem(s) studied	Amyloid light-chain amyloidosis
Intervention	EGCG capsules 400-1200 mg in increasing dosages or placebo for 1 year
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Epigallocatechin-3-gallate
Primary outcome measure	Left ventricular mass, measured by cardiac MRI
Secondary outcome measures	1. Quality of life, measured using the EORTC-QLQ-C30 2. Left ventricle (LV) end diastolic and end systolic volumes with resulting ejection fraction, measured by cardiac MRI 3. Cardiac function parameters (calculated left ventricular mass, Tissue DI, TAPSE, MAPSE) 4. Cardiac biomarkers (cardiac troponin T hsTNT, NTproBNP) 5. 6-minute walk distance 6. Organ response in other affected organs, Gertz et al., 2005; standard criteria 7. Improvement of hematological remission 8. Overall survival 9. Correlation of epigallocatechin gallate (EGCG) serum levels with organ response 10. Number of adverse events according to Common Toxicity Criteria (CTC) version 4.0 Measured 12 months after the start of treatment
Overall study start date	01/12/2012
Completion date	10/11/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	38
Key inclusion criteria	1. Biopsy proven systemic AL amyloidosis 2. Cardiac involvement with septum thickness >12 mm (without other causes as published by Gertz et al) 3. Hypertension or other potential causes of left ventricular hypertrophy 4. Previously treated with chemotherapy 5. Induced at least a very good partial remission of the underlying monoclonal plasma cell or B cell disorder
Key exclusion criteria	1. Age < 18 years 2. Concomitant multiple myeloma stage II and III (Salmon and Durie) 3. Concurrent chemotherapy necessary 4. Time to last chemotherapy > 6 months 5. Chronic liver disease 6. Bilirubin > 1,5 mg/dl 7. Not able to visit Amyloidosis Clinic in Heidelberg every 3 months
Date of first enrolment	01/12/2012
Date of final enrolment	01/10/2016

Locations

Countries of recruitment

Germany

Study participating centre

Medical Department V

Heidelberg
D-69120
Germany

Sponsor information

Ruprecht-Karls-University of Heidelberg (Germany)
University/education

Medical Faculty, represented by Universitätsklinikum Heidelberg
Im Neuenheimer Feld 672
Heidelberg
D-69120
Germany

Email	irmtraud.guerkan@med.uni-heidelberg.de
"ROR"	https://ror.org/038t36y30

Funders

Funder type

Government

Bundesministerium für Bildung und Forschung FKZ: 01GM1107A
Government organisation / National government

Alternative name(s): Federal Ministry of Education and Research, BMBF
Location: Germany

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	To be confirmed at a later date
IPD sharing plan

Editorial Notes

22/11/2016: Plain English summary added.
08/11/2016: The overall trial end date has been updated from 30/11/2015 to 10/11/2017.