Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis (EpiCardiAL)

• ClinicalTrials.gov Identifier: NCT01511263
• Recruitment Status: Terminated
• First Posted: January 18, 2012
• Last Update Posted: March 21, 2018
• Sponsor: IRCCS Policlinico S. Matteo
• Information provided by (Responsible Party): Giampaolo Merlini, IRCCS Policlinico S. Matteo

Study Description

Brief Summary:

In a proportion of patients with AL amyloidosis there is no improvement of cardiac function despite hematologic response to treatment. The aim of the study is to assess whether treatment with EGCG increases the rate of cardiac response in patients with AL amyloidosis who completed chemotherapy.

Condition or disease	Intervention/treatment	Phase
Primary Amyloidosis of Light Chain Type	Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias); Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG	Phase 2

Detailed Description:

This will be a phase II open-label randomized trial. Patients with AL amyloidosis and cardiac involvement who have achieved at least partial hematologic response after chemotherapy will be randomized to receive standard supportive therapy (SST) or SST plus Epigallocatechin gallate (EGCG). After giving written informed consent, the patients will be evaluated for eligibility. Briefly, the subjects with a biopsy-proven diagnosis of AL amyloidosis who achieved at least partial response after chemotherapy, who are not planned to receive further chemotherapy and who have significant cardiac dysfunction will be considered eligible. The patients will be stratified according to the quality of hematologic response and to the severity of cardiac involvement. Following stratification, the patients will be randomized to receive SST or SST plus EGCG. The study comprises 3 periods: screening (including stratification and randomization), treatment (with evaluations of response every 2 months) followed by the end-of-treatment evaluation and follow-up. Therapy will continue for up to 1 year. After treatment patients will be followed for 3 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open-label Randomized Study of Dietary Supplement With Epigallocatechin Gallate (EGCG) to Improve Cardiac Dysfunction in Patients With AL Amyloidosis Who do Not Require Chemotherapy (EpiCardiAL)
• Actual Study Start Date: January 2012
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm A; The patients will be divided into 4 strata according to cardiac dysfunction and to the quality of hematologic response. After stratification the patients will be randomized (1:1) within each stratum to receive Standard Therapy alone (Arm A) or Standard Therapy plus Investigational Drug (Arm B).	Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias); Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated.
Experimental: Arm B; The patients will be divided into 4 strata according to cardiac dysfunction and to the quality of hematologic response. After stratification the patients will be randomized (1:1) within each stratum to receive Standard Therapy alone (Arm A) or Standard Therapy plus Investigational Drug (Arm B)	Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG; Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated. EGCG, 675 mg/day, oral, for one year.

Outcome Measures

Primary Outcome Measures :

1. Cardiac response [ Time Frame: 6 months ]
   The primary objective is to assess whether treatment with EGCG increases the rate of cardiac response following chemotherapy in patients with AL amyloidosis. The primary endpoint is cardiac response at 6 months.

Secondary Outcome Measures :

1. Rate of adverse events [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.
2. Rate of cardiac progression [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.
3. Time to cardiac progression [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.
4. Rate of cardiac events [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.
5. Time to cardiac events [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.
6. Survival [ Time Frame: 6 months ]
   The secondary objectives are to assess the safety of EGCG in cardiac AL amyloidosis, to determine whether EGCG can prevent or delay cardiac progression and to compare survival of patients receiving EGCG compared to subjects receiving SST.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Diagnosis of AL amyloidosis.
• Age ≥18 years.
• The patients must have been treated for AL amyloidosis attaining hematologic response.
• Evidence of cardiac involvement at echocardiography (mean left ventricular wall thickness >12 mm in the absence of other causes).
• NT-proBNP ≥650 ng/L

Exclusion Criteria:

• Non-AL (e.g. familial, senile) amyloidosis.
• Concomitant non-amyloid related clinically significant cardiac diseases.
• Need of further chemotherapy for AL amyloidosis.
• Estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m2.
• Uncontrolled infection.
• Inability to give informed consent.
• Previous or ongoing psychiatric illness (excluding reactive depression).
• Pregnant or nursing women.

Contacts and Locations

Locations

Italy

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

Pavia, Italy, 27100

Sponsors and Collaborators

IRCCS Policlinico S. Matteo

More Information

Additional Information:

Related Info 

Publications:

Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, Greipp PR, Witzig TE, Lust JA, Rajkumar SV, Fonseca R, Zeldenrust SR, McGregor CG, Jaffe AS. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004 Sep 15;22(18):3751-7.

Hunstein W. Epigallocathechin-3-gallate in AL amyloidosis: a new therapeutic option? Blood. 2007 Sep 15;110(6):2216.

Mereles D, Buss SJ, Hardt SE, Hunstein W, Katus HA. Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis. Clin Res Cardiol. 2010 Aug;99(8):483-90. doi: 10.1007/s00392-010-0142-x. Epub 2010 Mar 10.

Mereles D, Wanker EE, Katus HA. Therapy effects of green tea in a patient with systemic light-chain amyloidosis. Clin Res Cardiol. 2008 May;97(5):341-4. doi: 10.1007/s00392-008-0649-6. Epub 2008 Mar 3.

Merlini G, Palladini G. Amyloidosis: is a cure possible? Ann Oncol. 2008 Jun;19 Suppl 4:iv63-6. doi: 10.1093/annonc/mdn200. Review.

Palladini G, Barassi A, Klersy C, Pacciolla R, Milani P, Sarais G, Perlini S, Albertini R, Russo P, Foli A, Bragotti LZ, Obici L, Moratti R, Melzi d'Eril GV, Merlini G. The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood. 2010 Nov 4;116(18):3426-30. doi: 10.1182/blood-2010-05-286567. Epub 2010 Jul 19.

Palladini G, Campana C, Klersy C, Balduini A, Vadacca G, Perfetti V, Perlini S, Obici L, Ascari E, d'Eril GM, Moratti R, Merlini G. Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation. 2003 May 20;107(19):2440-5. Epub 2003 Apr 28.

• Responsible Party: Giampaolo Merlini, Director, Amyloidosis Research and Treatment Center, IRCCS Policlinico S. Matteo
• ClinicalTrials.gov Identifier: NCT01511263
• Other Study ID Numbers: AC-006-IT
• First Posted: January 18, 2012
• Last Update Posted: March 21, 2018
• Last Verified: March 2018

Keywords provided by Giampaolo Merlini, IRCCS Policlinico S. Matteo:

Epigallocatechin gallate; AL amyloidosis

Additional relevant MeSH terms:

Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias; Amiodarone; Anti-Arrhythmia Agents; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Vasodilator Agents; Potassium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Sodium Channel Blockers; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A Inhibitors