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

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

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.

Study Overview

• Status: Completed
• Conditions: Light Chain (AL) Amyloidosis; Cardiac Involvement
• Intervention / Treatment: Drug: Epigallocatechin-3-gallate (EGCG); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • University Hospital of Heidelberg; Medical Department V

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epigallocatechin-3-gallate (EGCG); 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); 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; Other Names: EGCG; Epigallocatechin gallate; Epigallocatechin 3-gallate; Tea catechin; Epigallocatechin-3-gallate
Placebo Comparator: Placebo; 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; 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; Other Names: Mannitol 99.5% + highly dispersed silicon dioxide 0.5%

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Florian Michel
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Principal Investigator: Stefan Schönland, MD, University Hospital of Heidelberg

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): October 11, 2017
• Study Completion (Actual): October 11, 2017

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): October 17, 2017
• Last Update Submitted That Met QC Criteria: October 16, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Amyloidosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Natriuretic Agents; Trace Elements; Micronutrients; Diuretics, Osmotic; Diuretics; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Mannitol; Epigallocatechin gallate; Silicon
• Other Study ID Numbers: TAME-AL; 2012-004520-38 (EudraCT Number)