REmodelling in Diabetic CardiOmapathy: Gender Response to PDE5i InhibiTOrs - Full Text View

Purpose

Pathophysiology of diabetic cardiomyopathy (DCM) is yet unclear and gender differences at baseline and a specific treatment have not been indicated. The investigators already demonstrated the positive impact of phosphodiesterase type 5A (PDE5A) inhibition in men. The investigators' study aims to characterize DCM, measuring molecular and neuroendocrine assessment to relate to intramyocardial metabolism and cardiac kinetic. The investigators will perform a randomized, placebo-controlled, double-blind study enrolling 164 diabetic patients (females and males) with DCM, to evaluate gender responses to 6 months of PDE5A inhibitors (PDE5Ai). The investigators' study will describe gender differences in DCM features. The proposed research will test whether PDE5Ai could become a new target for antiremodeling drugs and to discover a molecular pathways affected by this class of drugs and a network of circulating markers for the early diagnosis, monitoring and prediction of response to treatment of DCM.

Condition	Intervention	Phase
Diabetic Cardiomyopathy Diabetes Mellitus Type 2 Left Ventricular Hypertrophy	Drug: Tadalafil Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase IV Study on New Insights in Remodeling of Diabetic Cardiomyopathy: Gender Difference in Intramyocardial, Molecular and Neuroendocrine Assessment in Response to Chronic Inhibition of Cyclic GMP Phosphodiesterase 5A

Resource links provided by NLM:

MedlinePlus related topics: Cardiomyopathy Diabetes Complications Diabetic Heart Disease

Drug Information available for: Tadalafil

U.S. FDA Resources

Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:

Change from Baseline in Left Ventricular torsion (°) at 3 and 6 months [ Time Frame: 0 , + 3 months, + 6 months ] [ Designated as safety issue: No ]
Change of Left ventricular torsion (°) assessed through CMR with tagging before and after treatment to heart failure and gender differences

Secondary Outcome Measures:

Change from baseline in longitudinal shortening (Strain %) at 3 and 6 months [ Time Frame: time 0, +3 months, + 6 months ] [ Designated as safety issue: No ]
Change of cardiac strain (longitudinal shortening: strain %), and of parameters of cardiac geometry and performance assessed through CMR with tagging before and after treatment and gender differences
Change from baseline in Myocardial fibrosis at 3 and 6 months [ Time Frame: time 0, + 3 months, + 6 motnhs ] [ Designated as safety issue: Yes ]
Quantification of Myocardial fibrosis assessed with T1-mapping to establish a new parametersfor the characterization of DCM and treatment efficacy, assessed through CMR before and after treatment and gender differences
Change from baseline in Circulating microRNAs at 3 and 6 months [ Time Frame: Time 0, + 3 months, + 6 months ] [ Designated as safety issue: No ]
Assessment of circulating microRNAs from plasma and white blood cells (miR208, 499, 1, 133, 29, 223, 222) and correlation of their levels to basal torsion, strain and fibrosis (molecular markers predictors of disease).

Evaluation of miRNAs before and after treatment and and gender differences
Change from baseline in Circulating pro-fibrotic and pro-inflammatory chemokines at 3 and 6 months [ Time Frame: Time 0, + 3 months, + 6 months ] [ Designated as safety issue: No ]
Assessment of circulating pro-fibrotic and pro-inflammatory chemokines (MCP-1 and TGF-beta) and correlation to torsion, strain and fibrosis at time 0 and after treatment (markers predictors of disease progression and treatment efficacy) and differences in genders
Markers predictor of answer to treatment [ Time Frame: Time 3 and 6 months ] [ Designated as safety issue: No ]
Correlation of basal miRNAs and chemokines to cardiac parameters assessed through CMR after treatment (markers predictor of answer to treatment) and differences in genders
Therapeutic efficacy markers [ Time Frame: Time 3 and 6 months ] [ Designated as safety issue: No ]
Changes of circulating miRNAs from plasma and whit blood cells (miR208, 499, 1, 133, 29, 223, 222), after treatment (therapeutic efficacy measure) and changes in circulating chemokines. These results will be related to changes measured in cardiac torsion, strain, fibrosis and geometry (CMR). Gender differences will be analyzed
Risk of progression to heart failure [ Time Frame: Time 3 and 6 months ] [ Designated as safety issue: No ]
Stratification of patients in subgroup with respect to kinetic parameters (strain and torsion), cardiac fibrosis, geometry (LV mass and index of concentricity) and performance and metabolic parameters to identify patients at risk of progression to heart failure and differences in genders


Estimated Enrollment:	164
Study Start Date:	May 2014
Estimated Study Completion Date:	March 2018
Estimated Primary Completion Date:	January 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Tadalafil 5 mg	Drug: Tadalafil 5 mg/die (1 capsule) Other Name: Cialis 5 mg
Placebo Comparator: 2 Placebo 5 mg	Drug: Placebo Placebo 5mg/die (1 capsule) Other Name: Placebo

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Eligibility


Ages Eligible for Study:	35 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age 35-75 years;
Diagnosis of Type 2 Diabetes from at least 3 years;
HbA1c < 10%;
normal blood pressure or controlled hypertension;
BMI < 40;

Exclusion Criteria:

congenital or valvular cardiomyopathy;
ischemic heart disease;
endocrine diseases: male hypogonadism, hyperthyroidism, adrenal diseases, pituitary diseases
proliferative retinopathy or autonomic neuropathy;
contraindications to sildenafil use or CMR imaging;

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803828

Contacts


Contact: Andrea M Isidori, MD, PhD	39-06-4997-0540	andrea.isidori@uniroma1.it

Locations


Italy
Dipartimento di Medicina Sperimentale - Sezione di Fisiopatologia Medica - Sapienza Università di Roma	Recruiting
Rome, Italy, 00161
Contact: Andrea M Isidori, MD,PhD 39-06-4997-0540 andrea.isidori@uniroma1.it
Principal Investigator: Andrea M Isidori, MD,PhD
Sub-Investigator: Elisa Giannetta, MD,PhD

Sponsors and Collaborators

University of Roma La Sapienza

Investigators


Principal Investigator:	Andrea M Isidori, MD, PhD	University of Roma La Sapienza

More Information

Additional Information:

Department Web Site This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	Andrea M. Isidori, Professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier:	NCT01803828 History of Changes
Other Study ID Numbers:	RECOGITO
Study First Received:	February 26, 2013
Last Updated:	July 7, 2014
Health Authority:	Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:


Diabetic Cardiomyopathy Genders Phosphodiesterase 5A inhibitors miRNAs Chemokines

Additional relevant MeSH terms:


Cardiomyopathies Diabetes Mellitus, Type 2 Diabetic Cardiomyopathies Hypertrophy, Left Ventricular Cardiomegaly Cardiovascular Diseases Diabetes Complications	Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Heart Diseases Hypertrophy Metabolic Diseases Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on March 03, 2015

REmodelling in Diabetic CardiOmapathy: Gender Response to PDE5i InhibiTOrs (RECOGITO)