Daily Tadalafil on Body Fat and Lean Mass
Condition: Obesity; Sexual Dysfunction
Study type: Interventional
Phase: Phase 4

Summary: 
      Data confirming a role for PDE5 in adipocyte biology in vitro have been recently reported.
      However, a better understanding of the complex role of PDE5 in fat metabolism and whole body
      homeostasis requires the use of transgenic animal models either lacking or overexpressing
      PDE5 in adipose tissue. This will clarify the role of PDE5 in adipose expansion and
      metabolism, and also in glucose homeostasis and vascular function in vivo. Analysis of
      expression and activity of PDE5 in different sites of human adipose tissue (i.e. visceral vs.
      subcutaneous), and also in different metabolic conditions (i.e. high-fat diet vs. low calorie
      intake) could reveal if PDE5 can be considered to be a reliable 'marker' of metabolic
      dysfunction of the adipocyte. Importantly, chronic treatment with the PDE5 inhibitor
      sildenafil in a mouse model of diet-induced insulin resistance caused a significant
      improvement in insulin sensitivity . Also, in humans chronic exposure to tadalafil confirmed
      an improvement of insulin sensitivity in men with erectile dysfunction. However, the efficacy
      of long-term treatment with PDE5i awaits demonstration in human metabolic diseases such as
      obesity and insulin resistance.

      The primary purpose of the study is to investigate the effects of tadalafil taken once a day
      on body composition in men with sexual distress and/or erectile dysfunction.
    

Detailed description: 
      Study design: open-label, randomized controlled study Study duration: 16 weeks (8 active
      treatment + 8 follow-up)

      At baseline, after 8 and 16 weeks the following evaluations will be assessed: general
      physical examination and anthropometric parameters i.e., body weight (BW), height, BMI, and
      waist circumference (WC). Every eight weeks, body composition was calculated by using a whole
      body dual-energy X-ray absorptiometry (DEXA-HOLOGIC QDR-1000) according to the instructions
      of the manufacturer and standardized procedures, and the individual Total Fat Mass (FM)
      variation has been expressed as delta-variation (%) from baseline. Abdominal fat mass
      (distrectual, described as R1) was calculated by using arbitrary area of the square chosen by
      tracing of an ideal line joining last inferior ribs and anterior superior iliac spines.
      Calibration with the manufacturer's spine phantom and quality control analysis were performed
      daily. Fat Mass was expressed in grams per square centimeter (g/cm2) and result expressed as
      variation in percentage. Secondary outcomes were variations forom baseline of IIEF-5, total
      testosterone, estradiol and testosterone /estradiol ratios.

      STATISTICAL EVALUATION With a two-sided alpha value of 5% and power of 90%, a sample size of
      20 subjects per arm would be able to detect a 2% variation in the percentage of body lean and
      fat mass from the baseline at upper waist section (for fat mass) and overall body composition
      (for lean mass). Also, we tested for the differences between treatment groups by using
      analysis of variance for repeated measures. Statistical analysis was performed by using the
      computer statistical package SPSS 11.0 (SPSS Inc., Chicago, IL).
    

Intervention name(s): Tadalafil; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks; Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks
Other intervention name(s): Cialis
Intervention MeSH terms: Tadalafil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment