Ignite Creation Date:
2024-05-06 @ 7:52 AM
Last Modification Date:
2024-10-26 @ 11:53 AM
Study NCT ID:
NCT02611258
Status:
COMPLETED
Last Update Posted:
2023-05-16
First Post:
2015-11-16
Brief Title:
Endocrine Cardiomyopathy in Cushing Syndrome Response to Cyclic GMP PDE5 inhibitOrs
Sponsor:
Andrea M Isidori
Organization:
University of Roma La Sapienza
Study Overview
Official Title:
Study on New Insights in Remodeling of Endocrine Cardiomyopathies Intramyocardial Molecular and Neuroendocrine Assessment in Response to Chronic Inhibition of Cyclic GMP Phosphodiesterase 5A in Cushings Syndrome
Status:
COMPLETED
Status Verified Date:
2023-05
Last Known Status:
None
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:
ERGO
Brief Summary:
Pathophysiology of Cushings Syndrome CS cardiomyopathy is yet unclear and a specific treatment have not been indicated It was already demonstrated the positive impact of phosphodiesterase type 5A PDE5A inhibition in several models of cardiomyopathy and in a model of endocrine cardiomyopathy due to type 2 diabetes mellitus In this patients with diabetic cardiomyopathy it was demonstrated an improvement in cardiac kinetic geometry and performance parameters and reduction of the ambulatory measurement of waist circumference
This represents the first study that evaluate heart remodeling and performance changes and metabolicimmunologicalmolecular parameters after 5-months of Tadalafil 20 mg in Cushings Syndrome cardiomyopathy The proposed research will test whether phosphodiesterase 5A inhibition could become a new target for anti-remodeling drugs and to discover molecular pathways affected by this class of drugs and a network of circulating markers miRNA for the early diagnosis of Cushings Syndrome cardiomyopathy
The investigators hypothesize that
the signal molecules cGMP and cAMP could underlie the hypertrophicprofibrotic triggers related to this model of endocrine cardiomyopathy and that chronic inhibition of PDE5 activating cGMP signaling pathways could improve cardiac remodeling due to CS
PDE5 inhibition could have a role in lipolytic regulation
neuroendocrine eg natriuretic peptides and metabolic markers and chemokines eg MCP-1 TGF-ß might relate with left ventricular remodeling in CS
there are neuroendocrine eg natriuretic peptides metabolic markers and chemokines eg MCP-1 TGF-ß related to cardiac disease in CS
miRNA expression miR-208a 499 1 133 126 29 233 222 4454 might relate with left ventricular remodeling in CS
This represents the first study that evaluate heart remodeling and performance changes and metabolicimmunologicalmolecular parameters after 5-months of Tadalafil 20 mg in Cushings Syndrome cardiomyopathy The proposed research will test whether phosphodiesterase 5A inhibition could become a new target for anti-remodeling drugs and to discover molecular pathways affected by this class of drugs and a network of circulating markers miRNA for the early diagnosis of Cushings Syndrome cardiomyopathy
The investigators hypothesize that
the signal molecules cGMP and cAMP could underlie the hypertrophicprofibrotic triggers related to this model of endocrine cardiomyopathy and that chronic inhibition of PDE5 activating cGMP signaling pathways could improve cardiac remodeling due to CS
PDE5 inhibition could have a role in lipolytic regulation
neuroendocrine eg natriuretic peptides and metabolic markers and chemokines eg MCP-1 TGF-ß might relate with left ventricular remodeling in CS
there are neuroendocrine eg natriuretic peptides metabolic markers and chemokines eg MCP-1 TGF-ß related to cardiac disease in CS
miRNA expression miR-208a 499 1 133 126 29 233 222 4454 might relate with left ventricular remodeling in CS
Detailed Description:
Mechanisms of action and evolutionary progression of Cushings Syndrome CS cardiomyopathy are not yet been well elucidated and a specific treatment has not been identified Our study aims to characterize the CS cardiomyopathy in terms of measuring the cardiac kinetic and performance parameters tagged Cardiac Magnetic Resonance Imaging fibrosis T1-mapping technique Our study will evaluate if PDE5A inhibition could become a new target for antiremodeling drugs in CS treated patients that developed cardiac hypertrophy andor diastolic dysfunction independently of CS care accorded by current guidelines The investigators also will explore the potential mechanisms of action of PDE5Ai if exerted on cardiac tissue directly and contemporary also on other secondary pathways analyzing vascular endothelial or metabolic markers
A multidisciplinary approach will allow identifying a cluster of cardiovascular NT-ProBNP TGFb MCP1 and metabolic indices oxidative stress markers iNOS COX2 ROS RANTES and miRNAs whose variations will analyze together with the CS cardiomyopathy parameters measured at CMR and 2D-echocardiography
The Primary Objective is to evaluate the effects of PDE5Ai on Left Ventricular LV remodeling kinetic and geometry parameters at cine cardiac magnetic resonance CMR with tagging technique and contrast-enhanced andor at 2D echocardiography with Tissue Doppler Imaging and speckle tracking in patients with CS cardiomyopathy
Secondary Objectives
to measure the effect of PDE5Ai on LV fibrosis at T1-mapping CMR at baseline and after PDE5Ai administration
to measure the effect of PDE5Ai on cardiac performance at cine CMR and at 2D echocardiography with Tissue Doppler Imaging and speckle tracking at baseline and after PDE5Ai administration
to measure the effect PDE5Ai of circulating cardiac-inflammatory-metabolic-endothelial molecular markers
to measure the effect on bone and body composition
Patients will be screened at time 0 Follow up visits will take place every 4 weeks during treatment for 5 months and 1 month after the end of treatment
Diagnostic procedures will include
physical examination with measurement of anthropometric parameters weight waist circumference hip circumference and vital signs blood pressure heart rate
blood sampling for assessing glucose and lipid metabolism liver renal hematopoietic and coagulative function thyroid and androgen hormones ACTH and UFC inflammatory parameters cytokines monocyte subpopulations and microRNA
SF36 FSFI in women IEFF e IPSS in men questionnaires
cardiac exam electrocardiogram and echocardiogram
MOC with DEXA
magnetic resonance imaging MRI with contrast-enhanced cardiac T1-mapping for assessing cardiac fibrosis tagging for evaluating kinetic parameters torsion
This is a pilot study proof-of-concept then 10 patients are sufficient to detect the effect of PDE5Ai on cardiac remodeling in CS cardiomyopathy Estimating a 80 drop-out of the study due to the complexity of CS and the related neuro-psychiatric involvement 18 CS patients will be enrolled
All variables will be tested for normality Statistical analyzes will be performed using SPSS 180 The comparison before and after treatment will be made by non parametric Wilcoxon test The investigators will calculate the confidence interval for the prevalence of the effect measured by χ2 test or Fisher exact test The correlation was perfomed by Rho di Spearman
A multidisciplinary approach will allow identifying a cluster of cardiovascular NT-ProBNP TGFb MCP1 and metabolic indices oxidative stress markers iNOS COX2 ROS RANTES and miRNAs whose variations will analyze together with the CS cardiomyopathy parameters measured at CMR and 2D-echocardiography
The Primary Objective is to evaluate the effects of PDE5Ai on Left Ventricular LV remodeling kinetic and geometry parameters at cine cardiac magnetic resonance CMR with tagging technique and contrast-enhanced andor at 2D echocardiography with Tissue Doppler Imaging and speckle tracking in patients with CS cardiomyopathy
Secondary Objectives
to measure the effect of PDE5Ai on LV fibrosis at T1-mapping CMR at baseline and after PDE5Ai administration
to measure the effect of PDE5Ai on cardiac performance at cine CMR and at 2D echocardiography with Tissue Doppler Imaging and speckle tracking at baseline and after PDE5Ai administration
to measure the effect PDE5Ai of circulating cardiac-inflammatory-metabolic-endothelial molecular markers
to measure the effect on bone and body composition
Patients will be screened at time 0 Follow up visits will take place every 4 weeks during treatment for 5 months and 1 month after the end of treatment
Diagnostic procedures will include
physical examination with measurement of anthropometric parameters weight waist circumference hip circumference and vital signs blood pressure heart rate
blood sampling for assessing glucose and lipid metabolism liver renal hematopoietic and coagulative function thyroid and androgen hormones ACTH and UFC inflammatory parameters cytokines monocyte subpopulations and microRNA
SF36 FSFI in women IEFF e IPSS in men questionnaires
cardiac exam electrocardiogram and echocardiogram
MOC with DEXA
magnetic resonance imaging MRI with contrast-enhanced cardiac T1-mapping for assessing cardiac fibrosis tagging for evaluating kinetic parameters torsion
This is a pilot study proof-of-concept then 10 patients are sufficient to detect the effect of PDE5Ai on cardiac remodeling in CS cardiomyopathy Estimating a 80 drop-out of the study due to the complexity of CS and the related neuro-psychiatric involvement 18 CS patients will be enrolled
All variables will be tested for normality Statistical analyzes will be performed using SPSS 180 The comparison before and after treatment will be made by non parametric Wilcoxon test The investigators will calculate the confidence interval for the prevalence of the effect measured by χ2 test or Fisher exact test The correlation was perfomed by Rho di Spearman
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2015-004497-15 | EUDRACT_NUMBER | None | None |