Endocrine Cardiomyopathy in Cushing Syndrome: Response to Cyclic GMP PDE5 inhibitOrs
Status:
Unknown status
Trial end date:
2019-06-01
Target enrollment:
Participant gender:
Summary
Pathophysiology of Cushing's 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
metabolic/immunological/molecular parameters after 5-months of Tadalafil 20 mg in Cushing's
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 Cushing's Syndrome cardiomyopathy.
The investigators hypothesize that:
- the signal molecules cGMP and cAMP could underlie the hypertrophic/profibrotic 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 (e.g. natriuretic peptides) and metabolic markers and chemokines (e.g.
MCP-1, TGF-ß) might relate with left ventricular remodeling in CS;
- there are neuroendocrine (e.g. natriuretic peptides), metabolic markers and chemokines
(e.g. 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;