Daily Tadalafil on Body Fat and Lean Mass

Obesity Clinical Trial

— TADBODY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02554045
• Other study ID #: FDAAA 801
• Status: Completed
• Phase: Phase 4
• First received: September 8, 2015
• Last updated: October 25, 2016
• Start date: January 2015
• Est. completion date: September 2015

Study information

• Verified date: October 2016
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Obesity
• Sexual Dysfunction

Intervention

Drug:
• Tadalafil
Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks
• Placebo
Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

References & Publications (3)

Aversa A, Caprio M, Antelmi A, Armani A, Brama M, Greco EA, Francomano D, Calanchini M, Spera G, Di Luigi L, Rosano GM, Lenzi A, Migliaccio S, Fabbri A. Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression in human adipocytes in — View Citation

Aversa A, Fittipaldi S, Bimonte VM, Wannenes F, Papa V, Francomano D, Greco EA, Lenzi A, Migliaccio S. Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model. J Endocrinol Invest. 2016 Feb;39(2) — View Citation

Porst H, Brock GB, Kula K, Moncada I, Montorsi F, Basson BR, Kinchen K, Aversa A. Effects of once-daily tadalafil on treatment satisfaction, psychosocial outcomes, spontaneous erections, and measures of endothelial function in men with erectile dysfunctio — View Citation

Outcome

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