Ignite Creation Date:
2024-05-06 @ 5:00 PM
Last Modification Date:
2024-10-26 @ 2:20 PM
Study NCT ID:
NCT05167799
Status:
UNKNOWN
Last Update Posted:
2021-12-22
First Post:
2021-12-07
Brief Title:
Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure
Sponsor:
Ospedale C G Mazzoni
Organization:
Ospedale C G Mazzoni
Study Overview
Official Title:
Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction a Multicentre Registry
Status:
UNKNOWN
Status Verified Date:
2021-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AMY-CCM
Brief 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 andor 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None