REmodelling in Diabetic CardiOmapathy: Gender Response to PDE5i InhibiTOrs

NCT01803828 | Completed Phase 4

• 1 other identifier: RECOGITO
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Cardiomyopathy; Diabetes Mellitus Type 2

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Left Ventricular torsion (°) at 5 months

  Change of Left ventricular torsion (°) assessed through CMR with tagging before and after treatment to heart failure and gender differences

  time 0, +5 months

Secondary Outcomes (8)

• Change from baseline in cardiac shortening (Strain %) at 5 months

  time 0, + 5 months

• Change from baseline in Myocardial fibrosis at 5 months

  time 0, +5 months

• Change from baseline in Circulating pro-fibrotic and pro-inflammatory chemokines at 5 months

  Time 0, +5 months

• Peripheral immunological profile

  time 0 and +5 months

• Gender differences in molecular, immunological and cardiac morpho-functional profile.

  time 0 and +5 months

Study Arms (2)

Drug Group (Tadalafil)

ACTIVE COMPARATOR

Tadalafil 20 mg

Drug: Tadalafil

Placebo Group (PLC)

PLACEBO COMPARATOR

Placebo 20 mg

Drug: Placebo

Interventions

Tadalafil DRUG

20 mg/die (1 capsule)

Also known as: Cialis 20 mg

Drug Group (Tadalafil)

Placebo DRUG

Placebo 20 mg/die (1 capsule)

Placebo Group (PLC)

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

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

Rome, 00161, Italy

Location

Related Publications (1)

• Pofi R, Giannetta E, Feola T, Galea N, Barbagallo F, Campolo F, Badagliacca R, Barbano B, Ciolina F, Defeudis G, Filardi T, Sesti F, Minnetti M, Vizza CD, Pasqualetti P, Caboni P, Carbone I, Francone M, Catalano C, Pozzilli P, Lenzi A, Venneri MA, Gianfrilli D, Isidori AM. Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial. Sci Transl Med. 2022 Jun 15;14(649):eabl8503. doi: 10.1126/scitranslmed.abl8503. Epub 2022 Jun 15.

  PMID: 35704597 DERIVED

Related Links

• Department Web Site

MeSH Terms

Conditions

Diabetic Cardiomyopathies; Diabetes Mellitus, Type 2; Inflammation; Diabetes Complications

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Andrea M Isidori, MD, PhD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: March 4, 2013
• Study Start: May 1, 2014
• Primary Completion: January 1, 2019
• Study Completion: July 1, 2019
• Last Updated: July 10, 2019

Record last verified: 2019-07

Locations

IT (1)