Daily Tadalafil on Body Fat and Lean Mass

Study Overview
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Brief Summary
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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
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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).

Official Title
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Effects of Daily Tadalafil on Body Composition in Men With Sexual Distress

Conditions
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Obesity, Sexual Dysfunction

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects greater than 18 years with any BMI who volunteered to enter the study because of the presence of sexual distress and/or mild erectile dysfunction. Exclusion Criteria: Any concomitant treatment during the prior three months, changes in lifestyle, diet or physical exercise attended within the 16 weeks of study duration; patients actively or potentially trying to start a family or requiring fertility treatment; significant hepatic, respiratory, hematological or renal disease; history of drug or alcohol abuse; history or presence of any cancer; any other reason, which the investigator feels, precludes safe inclusion of the patient.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tadalafil<br>Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks | Drug: Tadalafil<br>* Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks<br>* Other names: Cialis;|
| Placebo Comparator: Placebo<br>Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks | Drug: Placebo<br>* Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation in lean and fat mass (overall and as evaluated by whole body DEXA Hologic-QDR1000 | Changes from baseline in the percentage of lean (overall estimation) and fat mass (abdominal area) and vs. control group as evaluated by whole body dual-energy X-ray absorptiometry (DEXA-HOLOGIC QDR-1000). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sexual domains (IIEF-5 scores) | Variation from baseline and vs control group of the IIEF-5 scores | 8 weeks | 
| Body Mass Index (BMI) | variation of BMI (Kg/m) | 8 weeks | 
| Hormonal variations from baseline and vs control group (Testosterone estradiol levels) | Plasma Testosterone and estradiol levels as evaluated by Radioimmunoassay | 8 weeks |