Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes

NCT00692237 | Completed Phase 4 Results DMC

• 1 other identifier: 746/07
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 Diabetes Mellitus (T2DM) represents a model of endothelial dysfunction, where chronic nitric oxide deprivation, hyperglycaemia and hyperinsulinemia and fibrogenic mediators lead to cardiovascular remodelling associated with diabetic cardiomyopathy and in consequence to secondary complications of diabetes. Specific anti-oxidative and anti-fibrotic therapies are not currently available. Sildenafil (Viagra) has demonstrated the capability of significantly improving endothelial dysfunction and cardiac fibrosis in experimental animal models. The purpose of the present study is performed to establish the effect of chronic high dose sildenafil treatment on heart performance in diabetic subjects.

Conditions

Diabetes Mellitus, Type 2; Endothelial Dysfunction

Keywords

Type 2 diabetes mellitus; Endothelial dysfunction; Sildenafil

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Torsion Defined as Change in Ventricular Mid-wall Rotation (°) Measured by Cine-Cardiac Magnetic Resonance (CMR) Imaging With Tagging, Before and After Three Months of Treatment With Sildenafil and Placebo (100 mg/Day).

  Diabetic cardiomyopathy and hypertrophy are characterized by an increase in cardiac torsion Normal value of rotation are \< 12°; in hypertrophic heart such values can raise up to 20-25°. A reduction in left ventricular wall rotation is a sign of improvement after removal of known causes of hypertrophy (for example after surgical repair of aortic stenosis). Based on previous studies a reduction of 3 degrees (°) is considered clinically significant.

  0 and + 3 months

Secondary Outcomes (1)

• Ejection Fraction (EF) Defined as the Volume of Blood Ejected With Each Beat Was Measured on Cine-Cardiac Magnetic Resonance (CMR) Images Before and After Three Months Treatment With Sildenafil and Placebo (100 mg/Day).

  0 and + 3 months

Study Arms (2)

1

ACTIVE COMPARATOR

Sildenafil 100 mg

Drug: Sildenafil

2

PLACEBO COMPARATOR

Placebo 100 mg

Drug: Placebo

Interventions

Sildenafil DRUG

100 mg daily (3 capsules/day)

Also known as: - Viagra 25 mg, - Viagra 50 mg

1

Placebo DRUG

Placebo 100 mg (3 capsules/day)

2

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 2 diabetes mellitus
• Patients age 35-75
• Metabolic control of diabetes by diet or oral treatment (unmodified in the last 3 months)
• Blood pressure \<160/100 mmHg, including subjects with controlled hypertension, treated with ACE-inhibitors/sartans, unmodified in the last 3 months

You may not qualify if:

• Participation in another study with an investigational drug or device
• HbA1c \>12%
• Alterations during ECG stress examination
• Current use of nitrate agents
• Proliferative retinopathy
• Patients with history of cardiovascular and malignant disease
• Psychosocial disturbance
• Alcohol or drug dependence
• Allergy or hypersensitivity to sildenafil or other Phosphodiesterase inhibitors.

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Dipartimento di Fisiopatologia Medica - Policlinico Umberto I

Rome, 00161, Italy

Location

Related Publications (4)

• Giannetta E, Isidori AM, Galea N, Carbone I, Mandosi E, Vizza CD, Naro F, Morano S, Fedele F, Lenzi A. Chronic Inhibition of cGMP phosphodiesterase 5A improves diabetic cardiomyopathy: a randomized, controlled clinical trial using magnetic resonance imaging with myocardial tagging. Circulation. 2012 May 15;125(19):2323-33. doi: 10.1161/CIRCULATIONAHA.111.063412. Epub 2012 Apr 11.

  PMID: 22496161 RESULT

• Pofi R, Giannetta E, Galea N, Francone M, Campolo F, Barbagallo F, Gianfrilli D, Venneri MA, Filardi T, Cristini C, Antonini G, Badagliacca R, Frati G, Lenzi A, Carbone I, Isidori AM. Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study. JACC Cardiovasc Imaging. 2021 Jun;14(6):1130-1142. doi: 10.1016/j.jcmg.2020.10.009. Epub 2020 Nov 18.

  PMID: 33221242 DERIVED

• Venneri MA, Barbagallo F, Fiore D, De Gaetano R, Giannetta E, Sbardella E, Pozza C, Campolo F, Naro F, Lenzi A, Isidori AM. PDE5 Inhibition Stimulates Tie2-Expressing Monocytes and Angiopoietin-1 Restoring Angiogenic Homeostasis in Diabetes. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2623-2636. doi: 10.1210/jc.2018-02525.

  PMID: 31102457 DERIVED

• Mandosi E, Giannetta E, Filardi T, Lococo M, Bertolini C, Fallarino M, Gianfrilli D, Venneri MA, Lenti L, Lenzi A, Morano S. Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes. Expert Opin Ther Targets. 2015;19(12):1617-22. doi: 10.1517/14728222.2015.1066337. Epub 2015 Jul 15.

  PMID: 26178526 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr Andrea Isidori
• Organization: Sapienza University of Rome

andrea.isidori@uniroma1.it

+39 0649970540

Study Officials

• Andrea Lenzi, MD, PhD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: June 4, 2008
• First Posted: June 6, 2008
• Study Start: January 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 8, 2013
• Results First Posted: May 15, 2012

Record last verified: 2013-05

Locations

IT (1)