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Diabetes & Vardenafil (DiVa)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02219646
Recruitment Status : Completed
First Posted : August 19, 2014
Last Update Posted : August 19, 2014
Information provided by (Responsible Party):
Manuela Simoni, Azienda USL Modena

Brief Summary:

Given the protective effect of nitric oxide (NO) on the endothelium and the results obtained so far in short-term, continuous treatment with phosphodiesterase-5 (PDE5) inhibitors on parameters of endothelial function, we hypothesise that chronic treatment with vardenafil can prevent or delay the deterioration of systemic endothelial function in patients with type 2 diabetes mellitus. The favourable effect of PDE5 inhibitors on sexual function in these patients has been convincingly demonstrated in the past. Here we hypothesise that vardenafil treatment can have beneficial effects on the vascular physiology in other body districts, possibly preventing the development of microangiopathy and atherosclerotic cardiovascular disease in these patients.

The main goal of this study is therefore to monitor the endothelial dysfunction during continuous treatment with vardenafil for 6 months; object of the study will be endothelin 1 and other known parameters of endothelial damage in newly diagnosed patients with type 2 diabetes mellitus.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus (T2DM) Endothelial Dysfunction Erectile Dysfunction Drug: Vardenafil Drug: Placebo Phase 2

Detailed Description:
Phosphodiesterase-5 (PDE5) inhibitors are currently used in the therapy of erectile dysfunction (ED), which is considered to be an early symptom of cardiovascular disease (CD). Impairment of endothelial function is the early lesion preceding atherosclerosis and is common to ED, CD and vascular complications of diabetes mellitus (DM). Continuous administration of the PDE5 inhibitors tadalafil or sildenafil for four weeks in men with increased cardiovascular risk or type 2 DM has been shown to improve endothelial function measured by flow-mediated dilation and reduction of inflammatory markers. The goal of this study is to investigate whether chronic, long-term treatment with vardenafil improves and/or prevents deterioration of systemic endothelial function in patients with type 2 DM. Study design: longitudinal, double-blind, randomised, placebo-controlled interventional study. Patients: 106 male patients (n determined by power analysis) with type 2 DM diagnosed and classified according to the guidelines of the European Association for the Study of Diabetes. Beside the antidiabetic treatment, patients will be randomly assigned to receive either placebo or vardenafil, 10 mg p.o. two times a day for 24 weeks. Exclusion criteria: all contraindications to treatment with PDE5 inhibitors. Age range: 40-60 years. Sample size determined by power analysis assuming variations of the primary end point of ± 10% from baseline at 0.05 α level with a power of 80%, a two-sided test and a dropout rate of 15%. Primary end point: serum endothelin 1 levels (decreased/not increased in the verum group vs. not decrease/increased in the placebo group). Other parameters and measurements: Complete clinical workup, weight, height, waist-hip ratio, serum lipids and glucose, hemoglobin glycated (HbA1c), micro- and macroalbuminuria, homocysteine, high reactive C-protein (hsCRP), interleukin-6 (IL-6), Tumor necrosis factor (TNF)α, fibrinogen, adiponectin, testosterone, sex hormone-binding globulin (SHBG) and estradiol. All parameters measured at baseline, 4 weeks, 12 weeks and 24 weeks on medication as well as 4 and 24 weeks after discontinuation of the study drug. Study duration: two years. Statistics: descriptive statistics, ANCOVA and multiple regression analysis or non-parametric tests as appropriate by STATA. Ethics: The trial will be registered. Ethics committee approval and patient informed consent will be obtained. Expected outcome and objective: Monitoring of endothelial function deterioration in type 2 DM during chronic administration of Vardenafil. Possibility for a long term-follow up study. Publication in a high impact factor journal.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Monitoring of Endothelial Dysfunction During Chronic Administration of Vardenafil in Patients With Type 2 Diabetes Mellitus: A Longitudinal, Randomised, Placebo-controlled, Double Blind, Phase II b, Clinical Trial
Study Start Date : March 2010
Actual Primary Completion Date : February 2013
Actual Study Completion Date : February 2014

Arm Intervention/treatment
Experimental: Vardenafil
The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Study Group were treated with vardenafil 10 mg twice/daily.
Drug: Vardenafil
Vardenafil 10 mg twice daily for six months
Other Name: Levitra

Placebo Comparator: Control
The study protocol consists of a Screening/Enrolment Phase lasting up to 4 weeks, a Treatment Phase of 24 weeks, and Follow-up/Observation Treatment-free Phase of 24 weeks after the Treatment Phase. During treatment phase, patients enrolled in the Control Group were treated with tablets twice/daily identical to the Study Group, but containing placebo.
Drug: Placebo
Placebo two tablets daily for 6 months

Primary Outcome Measures :
  1. Endothelin-1 [ Time Frame: "6 months" ]
    change in serum endothelin 1 concentration

Secondary Outcome Measures :
  1. Flow Mediated Dilation [ Time Frame: "baseline" ]
    Change of flow mediated dilation evaluated by ultrasonography at brachial artery

  2. Flow Mediated dilation (FMD) [ Time Frame: "6 months" ]
    Change of FMD levels

  3. Flow Mediated Dilation [ Time Frame: "One year" ]
    Change of FMD levels

Other Outcome Measures:
  1. carotid Intima Media Thickness [ Time Frame: "baseline" ]
    Change of ultrasonographic evaluation of intima-media thickness at both right and left carotid arteries

  2. carotid Intima Media Thickness (IMT) [ Time Frame: "6 months" ]
    Change in IMT levels

  3. carotid Intima Media Thickness [ Time Frame: "One year" ]
    change in IMT levels

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male gender
  • Signed written Consent Form
  • Type 2 diabetes mellitus diagnosed within 5 years before enrolment in the study
  • Body Mass Index (BMI) < 35
  • ED (severe, moderate or light according to the International Index of Erectile Function - erectile function domain score < 26 (Rosen et al. 1997))
  • Age range: 40-65 years.

Exclusion Criteria:

  • Systemic diseases except type 2 diabetes mellitus
  • Absence of ED
  • Psychiatric disorders
  • All contraindications to treatment with PDE5 inhibitors, such as retinitis pigmentosa, non-arteritic anterior ischaemic optic neuropathy, history of coronary artery disease, recent myocardial infarction, unstable angina, systemic arterial hypotension, nitric-oxide donors therapy, severe hepatic and renal failure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02219646

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Unit of Endocrinology Azienda USL
Modena, Italy, 41126
Sponsors and Collaborators
Azienda USL Modena
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Principal Investigator: Manuela Simoni, MD, PhD Azienda USL Modena
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Responsible Party: Manuela Simoni, Ordinary Professor, Azienda USL Modena Identifier: NCT02219646    
Other Study ID Numbers: EudraCT number 2009-014137-25
First Posted: August 19, 2014    Key Record Dates
Last Update Posted: August 19, 2014
Last Verified: August 2014
Keywords provided by Manuela Simoni, Azienda USL Modena:
Additional relevant MeSH terms:
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Erectile Dysfunction
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sexual Dysfunction, Physiological
Sexual Dysfunctions, Psychological
Mental Disorders
Vardenafil Dihydrochloride
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents