Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis

Primary Amyloidosis of Light Chain Type Clinical Trial

— EpiCardiAL  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01511263
• Other study ID #: AC-006-IT
• Status: Terminated
• Phase: Phase 2
• First received: January 10, 2012
• Last updated: March 20, 2018
• Start date: January 2012
• Est. completion date: July 2016

Study information

• Verified date: March 2018
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 86
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• Primary Amyloidosis of Light Chain Type

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo	Pavia

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Matteo

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac response	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.	6 months
Secondary	Rate of adverse events	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 months
Secondary	Rate of cardiac progression	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 months
Secondary	Time to cardiac progression	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 months
Secondary	Rate of cardiac events	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 months
Secondary	Time to cardiac events	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 months
Secondary	Survival	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 months

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