Primary Amyloidosis of Light Chain TypePhase 2EpiCardiALNCT01511263
Epigallocatechingallate (EGCG) in Cardiac AL Amyloidosis
A Phase 2 study testing Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias) and Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Amyloidosis of Light Chain Type
- What is being tested?
- Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias) and Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2012to Jul 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
Pavia, 27100
About this study
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)
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.
Read the 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.
- Conditions
- Primary Amyloidosis of Light Chain Type
- Being tested
- 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
- Keywords
- Epigallocatechin gallate, AL amyloidosis
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)Drug
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 EGCGDrug
Antiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated.
EGCG, 675 mg/day, oral, for one year.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | 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). Receives: Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias) |
| Arm B | Experimental | 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) Receives: Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (6)
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Primary Amyloidosis of Light Chain TypeStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giampaolo Merlini, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01511263
- Sponsor's protocol ID
- AC-006-IT
- Acronym
- EpiCardiAL
- Status last verified
- Mar 2018
- First submitted
- 10 Jan 2012
- Last updated
- 21 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1200/JCO.2004.03.029.
PubMed 15365071Hunstein 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.
PubMed 17785589Mereles 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.
PubMed 20221615Mereles 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.
PubMed 18317666Merlini 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.
PubMed 18519408Palladini 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.
PubMed 20644111Palladini 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.
PubMed 12719281
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01511263
- Acronym / sponsor ID
- EpiCardiAL / AC-006-IT
- Conditions
- Primary Amyloidosis of Light Chain Type
- Keywords
- Epigallocatechin gallate, AL amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Jan 2012 (actual)
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 18 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias)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 B | Experimental | Drug: Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCGThe 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Arm A |
| Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCGAntiarrhythmic drugs (i.e. amiodarone), angiotensins which transform inhibitor enzymes, and/or beta-blockers if tolerated. EGCG, 675 mg/day, oral, for one year. | Drug | Arm B |
Primary outcome
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.
6 secondary outcomes
Rate of adverse events
Time frame: 6 months
Rate of cardiac progression
Time frame: 6 months
Time to cardiac progression
Time frame: 6 months
Rate of cardiac events
Time frame: 6 months
Time to cardiac events
Time frame: 6 months
Survival
Time frame: 6 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2018.
- Background: PubMed 15365071Dispenzieri 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.
- Background: PubMed 17785589Hunstein 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.
- Background: PubMed 20221615Mereles 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.
- Background: PubMed 18317666Mereles 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.
- Background: PubMed 18519408Merlini 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.
- Background: PubMed 20644111Palladini 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.
- Background: PubMed 12719281Palladini 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhithmias) and Diuretics (plus antiarrhythmic drugs, i.e. amiodarone, in case of complex ventricular arrhythmias) plus EGCG in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac response (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01511263, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2018.