Diabetes & Vardenafil
Condition: Type 2 Diabetes Mellitus (T2DM); Endothelial Dysfunction; Erectile Dysfunction
MeSH terms: Erectile Dysfunction; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Vardenafil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Vardenafil 10 mg twice daily for six months; Placebo two tablets daily for 6 months
Other intervention name(s): Levitra
Intervention MeSH terms: Vardenafil Dihydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: T2DM; ED