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

• ClinicalTrials.gov Identifier: NCT01803828
• Recruitment Status: Completed
• First Posted: March 4, 2013
• Last Update Posted: July 10, 2019
• Sponsor: University of Roma La Sapienza
• Information provided by (Responsible Party): Andrea M. Isidori, University of Roma La Sapienza

Study Description

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	Drug: Tadalafil; Drug: Placebo	Phase 4

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Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 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
• Actual Study Start Date: May 2014
• Actual Primary Completion Date: January 2019
• Actual Study Completion Date: July 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Drug Group (Tadalafil); Tadalafil 20 mg	Drug: Tadalafil; 20 mg/die (1 capsule); Other Name: Cialis 20 mg
Placebo Comparator: Placebo Group (PLC); Placebo 20 mg	Drug: Placebo; Placebo 20 mg/die (1 capsule)

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Left Ventricular torsion (°) at 5 months [ Time Frame: time 0, +5 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 cardiac shortening (Strain %) at 5 months [ Time Frame: time 0, + 5 months ]
   Change of cardiac 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 5 months [ Time Frame: time 0, +5 months ]
   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 pro-fibrotic and pro-inflammatory chemokines at 5 months [ Time Frame: Time 0, +5 months ]
   Assessment of circulating pro-fibrotic and pro-inflammatory chemokines 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
4. Peripheral immunological profile [ Time Frame: time 0 and +5 months ]
   Evaluation of immune function and circulating and cellular angiogenesis mediators predictive of disease progression and PDE5Ai treatment efficacy
5. Gender differences in molecular, immunological and cardiac morpho-functional profile. [ Time Frame: time 0 and +5 months ]
   Identify gender differences in molecular, immunological and imaging characterization of the DCM.
6. Effects of PDE5i on diabetic neuropathy [ Time Frame: time 0 and +5 months ]
   Identify possible effects of chronic treatment with PDE5i on diabetic neuropathy
7. Effects of PDE5i on diabetic nephropathy [ Time Frame: time 0 and +5 months ]
   Identify possible effects of chronic treatment with PDE5i on diabetic nephropathy
8. Effects of PDE5i on Body composition [ Time Frame: time 0 and +5 months ]
   Evaluation of the effect of PDE5Ai on body composition evaluated by DEXA scan.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• age 45-80 years;
• Diagnosis of Type 2 Diabetes from at least 3 years;
• HbA1c < 10%;
• normal blood pressure or controlled hypertension;
• BMI < 40;
• SIV ≥ 11 mm men, ≥ 10 women and/or diastolic dysfunction (PW-doppler and TDI)

Exclusion Criteria:

• current use of PDE5 inhibitors;
• congenital or valvular cardiomyopathy;
• ischemic heart disease;
• proliferative retinopathy;
• contraindications to tadalafil use (hypersensitivity to tadalafil, nitrates use, severe cardiovascular disorders such as unstable angina or severe heart failure, severe hepatic impairment, blood pressure <90/50 mmHg, recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmentosa);
• contraindications to CMR imaging with mdc (patients with implant such as cardiac pacemakers, insulin pumps, neurostimulators and cochlear implants, or metallic fragments, clips or devices, or severe renal failure with GFR < 30mL/min/1.73 m2);
• cronic or acute atrial fibrillation.

Contacts and Locations

Locations

Italy

Dipartimento di Medicina Sperimentale - Sezione di Fisiopatologia Medica - Sapienza Università di Roma

Rome, Italy, 00161

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 

• 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: July 10, 2019
• Last Verified: July 2019

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

Diabetic Cardiomyopathy; Genders; Phosphodiesterase 5A inhibitors; endothelial dysfunction; inflammation; diabetic complications

Additional relevant MeSH terms:

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