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Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis (EpiCardiAL)

Primary Purpose

Primary Amyloidosis of Light Chain Type

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)
Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG
Sponsored by
IRCCS Policlinico S. Matteo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Amyloidosis of Light Chain Type focused on measuring Epigallocatechin gallate, AL amyloidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm Description

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).

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
January 10, 2012
Last Updated
March 20, 2018
Sponsor
IRCCS Policlinico S. Matteo
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1. Study Identification

Unique Protocol Identification Number
NCT01511263
Brief Title
Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Terminated
Study Start Date
January 2012 (Actual)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Policlinico S. Matteo

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Amyloidosis of Light Chain Type
Keywords
Epigallocatechin gallate, AL amyloidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Arm B
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)
Intervention Description
Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated.
Intervention Type
Drug
Intervention Name(s)
Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG
Intervention Description
Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated. EGCG, 675 mg/day, oral, for one year.
Primary Outcome Measure Information:
Title
Cardiac response
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Rate of adverse events
Description
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.
Time Frame
6 months
Title
Rate of cardiac progression
Description
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.
Time Frame
6 months
Title
Time to cardiac progression
Description
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.
Time Frame
6 months
Title
Rate of cardiac events
Description
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.
Time Frame
6 months
Title
Time to cardiac events
Description
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.
Time Frame
6 months
Title
Survival
Description
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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
15365071
Citation
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. doi: 10.1200/JCO.2004.03.029.
Results Reference
background
PubMed Identifier
17785589
Citation
Hunstein W. Epigallocathechin-3-gallate in AL amyloidosis: a new therapeutic option? Blood. 2007 Sep 15;110(6):2216. doi: 10.1182/blood-2007-05-089243. No abstract available.
Results Reference
background
PubMed Identifier
20221615
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.
Results Reference
background
PubMed Identifier
18317666
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. No abstract available.
Results Reference
background
PubMed Identifier
18519408
Citation
Merlini G, Palladini G. Amyloidosis: is a cure possible? Ann Oncol. 2008 Jun;19 Suppl 4:iv63-6. doi: 10.1093/annonc/mdn200. No abstract available.
Results Reference
background
PubMed Identifier
20644111
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.
Results Reference
background
PubMed Identifier
12719281
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. doi: 10.1161/01.CIR.0000068314.02595.B2. Epub 2003 Apr 28.
Results Reference
background
Links:
URL
http://www.amiloidosi.it/
Description
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Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis

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