A Trial for the Treatment of Cardiac AL-Amyloidosis With the Green Tea Compound Epigallocatechin-3-gallate (TAME-AL)

Study Overview
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Brief Summary
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Efficacy and safety of epigallocatechin-3-gallate (EGCG) in patients with cardiac amyloid light-chain (AL) amyloidosis. Evaluation of clinical efficacy of EGCG intake using a pretest posttest comparison of left ventricular amyloid mass (g/m2) measured by cardiac MRI.

Official Title
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A Randomised Trial for the Treatment of Cardiac AMyloid Light-chain Amyloidosis With the Green Tea Compound Epigallocatechin-3-gallate (TAME-AL)

Conditions
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Light Chain (AL) Amyloidosis, Cardiac Involvement

Intervention / Treatment
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* Drug: Epigallocatechin-3-gallate (EGCG)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven systemic AL amyloidosis. Cardiac involvement with septum thickness more than 12 mm (without other causes as published by Gertz et al., hypertension or other potential causes of left ventricular hypertrophy) Previously treated with chemotherapy, induced at least a very good partial remission of the underlying monoclonal plasma cell or B cell disorder. GPT and GOT less than 3-times ULN. Life expectancy more than 12 month. Ability of subject to understand character and individual consequences of the clinical trail. Written informed consent. For women with childbearing potential and men, adequate contraception. Exclusion Criteria: Age less than 18 years. Concomitant multiple myeloma stage 2 and 3 (Salmon and Durie) Concurrent chemotherapy necessary Time to last chemotherapy more than 6 months. Chronic liver disease, Bilirubin over 1,5 mg/dl Not able to visit Amyloidosis Clinic in Heidelberg every 3 months. History of hypersensitivity to the investigational product or to any substance with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product. Participation in other clinical trials or observation period of competing trials, respectively. Pregnant or nursing women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epigallocatechin-3-gallate (EGCG)<br>EGCG 400 mg/d p.o. for 3 months; 800 mg/d p.o. for 3 months, 1200 mg/d p.o. for 6 months | Drug: Epigallocatechin-3-gallate (EGCG)<br>* Pharmaceutical formulation: capsules Dose: 400 mg/d for 3 months; 800 mg/d for 3 months, 1200 mg/d for 6 months Route of administration: p.o. Treatment duration: 12 months<br>* Other names: Epigallocatechin-3-gallate;|
| Placebo Comparator: Placebo<br>capsules Dose: 400 mg/d for 3 months; 800 mg/d for 3 months, 1200 mg/d for 6 months Route of administration: p.o. Treatment duration: 12 months | Drug: Placebo<br>* Pharmaceutical formulation: capsules Dose: 400 mg/d for 3 months; 800 mg/d for 3 months, 1200 mg/d for 6 months Route of administration: p.o. Treatment duration: 12 months<br>* Other names: Mannitol 99.5% + highly dispersed silicon dioxide 0.5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare the 12 month change in left ventricular mass | The primary analysis to compare the 12 month change in left ventricular mass between the two treatment arms will be performed by a one-sided two-sample t test at a significance level of 0.025. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life | Quality of Life, evaluated with EORTC-QLQ-C30 | baseline, 12 month | 
| safety of EGCG | Number of adverse events according to CTC criteria (Version 4.0) | 12 month | 
| change in cardiac biomarkers | cardiac troponin T (hsTNT), NTproBNP | Baseline, 12 Month | 
| improvement of hematological remission | Hematological Response according to Palladini et al 2012 | Baseline, 12 Month | 
| Organ response in affected organs other than heart | Organ response according to Gertz et al 2005 | Baseline, 12 Month | 
| Overall Survival |  | 12 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyloidosis