Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis (EpiCardiAL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by IRCCS Policlinico S. Matteo.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Giampaolo Merlini, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:
NCT01511263
First received: January 10, 2012
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by IRCCS Policlinico S. Matteo:

Primary Outcome Measures:
  • Cardiac response [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 86
Study Start Date: January 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01511263

Contacts
Contact: Giampaolo Merlini, Prof. +39(0)382502994 gmerlini@unipv.it
Contact: Giovanni Palladini, Dr. +39(0)382502994 g.palladini@smatteo.pv.it

Locations
Italy
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo Recruiting
Pavia, Italy, 27100
Contact: Giovanni Palladini, Dr.    +39(0)382502994    g.palladini@smatteo.pv.it   
Contact: Leda Roggeri, Dr.    +39(0)382502994    leda78@gmail.com   
Principal Investigator: Giampaolo Merlini, Prof.         
Sub-Investigator: Giovanni Palladini, Dr.         
Sponsors and Collaborators
IRCCS Policlinico S. Matteo
  More Information

Additional Information:
Publications:
Palladini G, Barassi A, Klersy C, Pacciolla R, Milani G, Sarais G, Perlini S, Albertini R, Russo P, Foli A, Bragotti LZ, Obici L, Moratti R, Melzi d'Eril GV and 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. Epub 2010 Jul 19.

Responsible Party: Giampaolo Merlini, Director, Amyloidosis Research and Treatment Center, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT01511263     History of Changes
Other Study ID Numbers: AC-006-IT
Study First Received: January 10, 2012
Last Updated: January 19, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS Policlinico S. Matteo:
Epigallocatechin gallate
AL amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Amiodarone
Anti-Arrhythmia Agents
Diuretics
Epigallocatechin gallate
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Natriuretic Agents
Physiological Effects of Drugs
Antioxidants
Protective Agents
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014