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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Diabetic Cardiomyopathy; Diabetes Mellitus Type 2; Left Ventricular Hypertrophy	Drug: Tadalafil; Drug: Placebo	Phase 4

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	164 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, 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
Study Start Date :	May 2014
Estimated Primary Completion Date :	June 2018
Estimated Study Completion Date :	January 2019

Arms and Interventions

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Arm	Intervention/treatment
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)

Outcome Measures

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Primary Outcome Measures :

1. Change from Baseline in Left Ventricular torsion (°) at 3 and 6 months [ Time Frame: 0 , + 3 months, + 6 months ]
   Change of Left ventricular torsion (°) assessed through CMR with tagging before and after treatment to heart failure and gender differences

Secondary Outcome Measures :

1. Change from baseline in longitudinal shortening (Strain %) at 3 and 6 months [ Time Frame: time 0, +3 months, + 6 months ]
   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
2. Change from baseline in Myocardial fibrosis at 3 and 6 months [ Time Frame: time 0, + 3 months, + 6 motnhs ]
   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
3. Change from baseline in Circulating microRNAs at 3 and 6 months [ Time Frame: Time 0, + 3 months, + 6 months ]

   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

4. Change from baseline in Circulating pro-fibrotic and pro-inflammatory chemokines at 3 and 6 months [ Time Frame: Time 0, + 3 months, + 6 months ]
   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
5. Markers predictor of answer to treatment [ Time Frame: Time 3 and 6 months ]
   Correlation of basal miRNAs and chemokines to cardiac parameters assessed through CMR after treatment (markers predictor of answer to treatment) and differences in genders
6. Therapeutic efficacy markers [ Time Frame: Time 3 and 6 months ]
   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
7. Risk of progression to heart failure [ Time Frame: Time 3 and 6 months ]
   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

Eligibility Criteria

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Ages Eligible for Study:	35 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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Additional Information:

Department Web Site 

Responsible Party:	Andrea M. Isidori, Professor, University of Roma La Sapienza
ClinicalTrials.gov Identifier:	NCT01803828 History of Changes
Other Study ID Numbers:	RECOGITO
First Posted:	March 4, 2013
Last Update Posted:	January 30, 2018
Last Verified:	January 2018

Keywords provided by Andrea M. Isidori, University of Roma La Sapienza:

Diabetic Cardiomyopathy; Genders; Phosphodiesterase 5A inhibitors; miRNAs; Chemokines

Additional relevant MeSH terms:

Diabetes Mellitus; Cardiomyopathies; Hypertrophy; Diabetes Mellitus, Type 2; Hypertrophy, Left Ventricular; Diabetic Cardiomyopathies; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases	Pathological Conditions, Anatomical; Cardiomegaly; Diabetes Complications; Tadalafil; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents