Amyloidosis CardiacAMY-CCMNCT05167799
Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure
An observational study of Amyloidosis Cardiac and Heart Failure, run by Ospedale C & G Mazzoni at 1 site in Italy.
Trial summary
The primary aim of this observational registry is to evaluate the efficacy of CCM in patients with heart failure with mid-range or reduced EF and diagnosis of TTR amyloidosis. The efficacy will be evaluated in terms of composite of occurrence of heart failure-related hospitalizations and/or acute intravenous… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Amyloidosis Cardiac, Heart Failure
- What is being tested?
- Cardiac Contractility Modulation (CCM)
- Type of treatment
- Medical device
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- 13 May 2021to 1 Jun 2024
- Phase
- Observational
- 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 to 100 years
- All sexes
- Adult, Older adult
Study population: This Registry includes patients with chronic, symptomatic heart failure with moderately-to-severely reduced left ventricular systolic function despite optimal pharmacological and electrical therapy, who have been diagnosed with TTR Cardiac Amyloidosis. The clinical trial study (prospective registry) will be conducted in accordance with the protocol, with the Helsinki Declaration and with the favorable opinion of the local Ethics Committee of the participating Centers.
Who may be able to join
- Age 18 years or older
- Male or a nonpregnant female
- All of the following: Established diagnosis of amyloid TTR Cardiomyopathy; baseline ejection fraction ≥25% and ≤45%; at least one hospitalization due to worsening heart failure over the year before entry into the registry.
- ICD if indicated
- PM if indicated
- Willing and able to return for all follow-up visits
Who cannot join
- AL amyloid cardiomyopathy
- Subjects who have a potentially correctible cause of heart failure (eg, Ischemic or valvular or congenital heart disease).
- Scheduled for CABG or PCI or has undergone a CABG within 90 d or PCI within 30 d.
- Myocardial infarction within 90 days
- Mechanical tricuspid valve
- Prior heart transplant
Show all 9Show fewer
- Chronic haemodialysis
- Familial TTR amyloidotic cardiomyopathy with significant polyneuropathy potentially eligible for Patirisan or Inotersen17
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Ospedale Mazzoni
Ascoli Piceno, Marche (AP), 63100
Procolo Marchese, +393921133283, procolo.marchese@gmail.com
About this study
Official title: Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction: a Multicentre Registry
The primary aim of this observational registry is to evaluate the efficacy of CCM in patients with heart failure with mid-range or reduced EF and diagnosis of TTR amyloidosis. The efficacy will be evaluated in terms of composite of occurrence of heart failure-related hospitalizations and/or acute intravenous interventions (IVI) at 12-month follow up compared to those reported 12 months before CCM implantation. Among the secondary endpoints, clinical functional status, quality of life, drug changes and Echocardiographic parameters will be evaluated and compared from baseline to follow up.
Read the detailed description
Amyloidosis represents a group of human degenerative diseases characterized by the deposition of aggregates of abnormally folded proteins in single or multi-organs. Cardiac amyloidosis is primarily associated with the systemic production and release of a number of amyloidogenic proteins, notably immunoglobulin light chain proteins (also known as amyloid light chain or AL) or transthyretin proteins (TTR). Notably, although myocardial dysfunction is generally understood as a result of infiltration by extracellular amyloid deposits, there is experimental evidence of direct cytotoxic effect, possibly due to oxidative stress.
Since neither HF optimal medical therapy nor HF devices seems to have a clear benefit in amyloid cardiomyopathy, this clinical setting needs to test other therapeutic options.
Randomized clinical trials have shown that Cardiac contractility modulation (CCM) may be considered as a concrete therapeutic option in patients with symptomatic Heart Failure (HF) despite optimal medical therapy (OMT), with Left Ventricular Ejection Fraction (LVEF) between 25% and 45%, with narrow QRS complex (<130ms).
CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca2+ cycling and stretch response genes. Specifically, 3-month on CCM therapy resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase (MAPK) and p21 Ras and increased expression of α-MHC, SERCA-2a, phospholamban, and ryanodine receptors. Notably, pre-clinical data suggest that triggering p38α MAPK autophosphorylation plays a crucial role in amyloidogenic light-chain mediated cellular oxidative stress, dysfunction and ultimately cell death in cardiomyocytes. Therefore CCM mechanism of action could be beneficial in cardiac amyloidosis but there are no data in this specific clinical setting.
- Conditions
- Amyloidosis Cardiac, Heart Failure
- Being tested
- Cardiac Contractility Modulation (CCM)
- Keywords
- Cardiac Amyloidosis, Heart Failure, Cardiac Contractility Modulation, CCM
- Medical subject headings
- Amyloid Neuropathies, Familial, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiac Contractility Modulation (CCM)Device
Patients will be implanted with CCM device according to indications, to improve Heart Failure symptoms and then enrolled in the Registry if they fullfil Inclusion and Exclusion Criteria (First of all if they are diagnosed with TTR Amyloidosis)
| Study group | Role | What they receive |
|---|---|---|
| Cardiac Amyloidosis patients | Patients with established diagnosis of amyloid TTR Cardiomyopathy, baseline ejection fraction ≥25% and ≤45%, at least one hospitalization due to worsening heart failure over the year before entry into the registry.
Already implanted with ICD or PM if needed, fullfilling the indication for CCM implantation. Receives: Device: Cardiac Contractility Modulation (CCM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of occurrence of hospitalizations due to worsening of heart failure and/or acute intravenous administrations of diuretics or inotropic drugs over the 12 months after entry into the registry.
The occurrence of any of the events mentioned (worsening of heart failure or intravenous intervention) involves reaching the endpoint
Measured: 12-month
Secondary outcomes (9)
Occurrence of clinical need to increase oral dose of diuretic drug and/or to add another diuretic drug class
Change from baseline to 2 weeks, 1,3, 6 and 12-month
Measured: 12-month
Occurrence of oral dose diuretic drug reduction
Change from baseline to 2 weeks, 1,3, 6 and 12-month
Measured: 12-month
NYHA class
Change from baseline to 2 weeks, 1,3, 6 and 12-month
Measured: 12-month
Distance walked at the 6-minute walking test
Change from baseline to 2 weeks, 1,3, 6 and 12-month in meters walked during the test
Measured: 12-month
Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score
Change from baseline to 2 weeks, 1,3, 6 and 12-month in the KCCQ-OS score
Measured: 12-month
Biomarker (NT-proBNP)
Change from baseline to 2 weeks, 1,3, 6 and 12-month in the biomarker level (pg/ml)
Measured: 12-month
Biomarker (HS-Troponin)
Change from baseline to 2 weeks, 1,3, 6 and 12-month in the biomarker level (ng/l)
Measured: 12-month
Echocardiographic parameters (Ejection Fraction)
Change from baseline to 2 weeks, 1,3, 6 and 12-month in EF (%)
Measured: 12-month
Echocardiographic parameters (End diastolic volume and End systolic volume)
Change from baseline to 2 weeks, 1,3, 6 and 12-month in End diastolic volume and End systolic volume respectively (ml)
Measured: 12-month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2021
- Study start13 May 2021
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Amyloidosis CardiacStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale C & G Mazzoni
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Procolo Marchese, Ospedale C & G Mazzoni
- Investigators
- Procolo Marchese, MD, Principal investigator, Ospedale Mazzoni (Ascoli Piceno)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05167799
- Sponsor's protocol ID
- AMYCCM190421
- Acronym
- AMY-CCM
- Status last verified
- Dec 2021
- First submitted
- 7 Dec 2021
- Last updated
- 22 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Shi J, Guan J, Jiang B, Brenner DA, Del Monte F, Ward JE, Connors LH, Sawyer DB, Semigran MJ, Macgillivray TE, Seldin DC, Falk R, Liao R. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4188-93. doi: 10.1073/pnas.0912263107. Epub 2010 Feb 11.
PubMed 20150510Brenner DA, Jain M, Pimentel DR, Wang B, Connors LH, Skinner M, Apstein CS, Liao R. Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res. 2004 Apr 30;94(8):1008-10. doi: 10.1161/01.RES.0000126569.75419.74. Epub 2004 Mar 25.
PubMed 15044325Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, Voss F, Becker R, Katus HA, Bauer A. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008 Feb;5(2):235-40. doi: 10.1016/j.hrthm.2007.10.016. Epub 2007 Oct 9.
PubMed 18242546Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.
PubMed 29754812Anker SD, Borggrefe M, Neuser H, Ohlow MA, Roger S, Goette A, Remppis BA, Kuck KH, Najarian KB, Gutterman DD, Rousso B, Burkhoff D, Hasenfuss G. Cardiac contractility modulation improves long-term survival and hospitalizations in heart failure with reduced ejection fraction. Eur J Heart Fail. 2019 Sep;21(9):1103-1113. doi: 10.1002/ejhf.1374. Epub 2019 Jan 16.
PubMed 30652394
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction: a Multicentre Registry
- ClinicalTrials.gov ID
- NCT05167799
- Acronym / sponsor ID
- AMY-CCM / AMYCCM190421
- Conditions
- Amyloidosis Cardiac, Heart Failure
- Keywords
- Cardiac Amyloidosis, Heart Failure, Cardiac Contractility Modulation, CCM
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Ospedale C & G MazzoniUniversity, hospital or other
- Study start
- 13 May 2021 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 22 Dec 2021 (actual)
- 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.
The primary aim of this observational registry is to evaluate the efficacy of CCM in patients with heart failure with mid-range or reduced EF and diagnosis of TTR amyloidosis. The efficacy will be evaluated in terms of composite of occurrence of heart failure-related hospitalizations and/or acute intravenous interventions (IVI) at 12-month follow up compared to those reported 12 months before CCM implantation. Among the secondary endpoints, clinical functional status, quality of life, drug changes and Echocardiographic parameters will be evaluated and compared from baseline to follow up.
Detailed description
Amyloidosis represents a group of human degenerative diseases characterized by the deposition of aggregates of abnormally folded proteins in single or multi-organs. Cardiac amyloidosis is primarily associated with the systemic production and release of a number of amyloidogenic proteins, notably immunoglobulin light chain proteins (also known as amyloid light chain or AL) or transthyretin proteins (TTR). Notably, although myocardial dysfunction is generally understood as a result of infiltration by extracellular amyloid deposits, there is experimental evidence of direct cytotoxic effect, possibly due to oxidative stress.
Since neither HF optimal medical therapy nor HF devices seems to have a clear benefit in amyloid cardiomyopathy, this clinical setting needs to test other therapeutic options.
Randomized clinical trials have shown that Cardiac contractility modulation (CCM) may be considered as a concrete therapeutic option in patients with symptomatic Heart Failure (HF) despite optimal medical therapy (OMT), with Left Ventricular Ejection Fraction (LVEF) between 25% and 45%, with narrow QRS complex (<130ms).
CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca2+ cycling and stretch response genes. Specifically, 3-month on CCM therapy resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase (MAPK) and p21 Ras and increased expression of α-MHC, SERCA-2a, phospholamban, and ryanodine receptors. Notably, pre-clinical data suggest that triggering p38α MAPK autophosphorylation plays a crucial role in amyloidogenic light-chain mediated cellular oxidative stress, dysfunction and ultimately cell death in cardiomyocytes. Therefore CCM mechanism of action could be beneficial in cardiac amyloidosis but there are no data in this specific clinical setting.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cardiac Amyloidosis patients | – | Device: Cardiac Contractility Modulation (CCM)Patients with established diagnosis of amyloid TTR Cardiomyopathy, baseline ejection fraction ≥25% and ≤45%, at least one hospitalization due to worsening heart failure over the year before entry into the registry. Already implanted with ICD or PM if needed, fullfilling the indication for CCM implantation. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- This Registry includes patients with chronic, symptomatic heart failure with moderately-to-severely reduced left ventricular systolic function despite optimal pharmacological and electrical therapy, who have been diagnosed with TTR Cardiac Amyloidosis. The clinical trial study (prospective registry) will be conducted in accordance with the protocol, with the Helsinki Declaration and with the favorable opinion of the local Ethics Committee of the participating Centers.
Key inclusion criteria (6 listed)
- Age 18 years or older
- Male or a nonpregnant female
- All of the following: Established diagnosis of amyloid TTR Cardiomyopathy; baseline ejection fraction ≥25% and ≤45%; at least one hospitalization due to worsening heart failure over the year before entry into the registry.
- ICD if indicated
- PM if indicated
Key exclusion criteria (9 listed)
- AL amyloid cardiomyopathy
- Subjects who have a potentially correctible cause of heart failure (eg, Ischemic or valvular or congenital heart disease).
- Scheduled for CABG or PCI or has undergone a CABG within 90 d or PCI within 30 d.
- Myocardial infarction within 90 days
- Mechanical tricuspid valve
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 |
|---|---|---|
| Cardiac Contractility Modulation (CCM)Patients will be implanted with CCM device according to indications, to improve Heart Failure symptoms and then enrolled in the Registry if they fullfil Inclusion and Exclusion Criteria (First of all if they are diagnosed with TTR Amyloidosis) | Device | Cardiac Amyloidosis patients |
Primary outcome
Composite of occurrence of hospitalizations due to worsening of heart failure and/or acute intravenous administrations of diuretics or inotropic drugs over the 12 months after entry into the registry.
Time frame: 12-month
The occurrence of any of the events mentioned (worsening of heart failure or intravenous intervention) involves reaching the endpoint
9 secondary outcomes
Occurrence of clinical need to increase oral dose of diuretic drug and/or to add another diuretic drug class
Time frame: 12-month
Occurrence of oral dose diuretic drug reduction
Time frame: 12-month
NYHA class
Time frame: 12-month
Distance walked at the 6-minute walking test
Time frame: 12-month
Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score
Time frame: 12-month
Biomarker (NT-proBNP)
Time frame: 12-month
Biomarker (HS-Troponin)
Time frame: 12-month
Echocardiographic parameters (Ejection Fraction)
Time frame: 12-month
Echocardiographic parameters (End diastolic volume and End systolic volume)
Time frame: 12-month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2021.
- Results publication: PubMed 20150510Shi J, Guan J, Jiang B, Brenner DA, Del Monte F, Ward JE, Connors LH, Sawyer DB, Semigran MJ, Macgillivray TE, Seldin DC, Falk R, Liao R. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4188-93. doi: 10.1073/pnas.0912263107. Epub 2010 Feb 11.
- Results publication: PubMed 15044325Brenner DA, Jain M, Pimentel DR, Wang B, Connors LH, Skinner M, Apstein CS, Liao R. Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res. 2004 Apr 30;94(8):1008-10. doi: 10.1161/01.RES.0000126569.75419.74. Epub 2004 Mar 25.
- Results publication: PubMed 18242546Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, Voss F, Becker R, Katus HA, Bauer A. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008 Feb;5(2):235-40. doi: 10.1016/j.hrthm.2007.10.016. Epub 2007 Oct 9.
- Results publication: PubMed 29754812Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.
- Results publication: PubMed 30652394Anker SD, Borggrefe M, Neuser H, Ohlow MA, Roger S, Goette A, Remppis BA, Kuck KH, Najarian KB, Gutterman DD, Rousso B, Burkhoff D, Hasenfuss G. Cardiac contractility modulation improves long-term survival and hospitalizations in heart failure with reduced ejection fraction. Eur J Heart Fail. 2019 Sep;21(9):1103-1113. doi: 10.1002/ejhf.1374. Epub 2019 Jan 16.
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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.
Procolo Marchese, MD principal investigator
Ospedale Mazzoni (Ascoli Piceno)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyloidosis Cardiac and Heart Failure, run by Ospedale C & G Mazzoni 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 6 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 22 Dec 2021. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Procolo Marchese, MD (+393921133283, procolo.marchese@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of occurrence of hospitalizations due to worsening of heart failure and/or acute intravenous administrations of diuretics or inotropic drugs over the 12 months after entry into the registry. (time frame: 12-month). 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 NCT05167799, which also lists 5 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 22 Dec 2021.