Daily Tadalafil on Body Fat and Lean Mass

NCT ID: NCT02554045

Last Updated: 2016-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2015-09-30

Brief 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).

Conditions

Obesity; Sexual Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Tadalafil

Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks

Group Type: ACTIVE_COMPARATOR

Tadalafil

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks

Interventions

Tadalafil

Patients will take tadalafil 2.5 mg tablet every morning for 8 weeks and then withdraw tadalafil for 8 weeks

Intervention Type: DRUG

Placebo

Patients will take placebo tablet every morning for 8 weeks and then withdraw placebo for 8 weeks

Intervention Type: DRUG

Other Intervention Names

Cialis

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Roma La Sapienza

OTHER

Sponsor Role: lead

Responsible Party

Antonio Aversa

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Aversa, MD-PHD

Role: PRINCIPAL_INVESTIGATOR

University of Roma La Sapienza

References

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):199-205. doi: 10.1007/s40618-015-0344-1. Epub 2015 Jul 2.

Reference Type: RESULT

PMID: 26134065 (View on PubMed)

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 dysfunction but naive to phosphodiesterase type 5 inhibitors. J Androl. 2012 Nov-Dec;33(6):1305-22. doi: 10.2164/jandrol.111.015289. Epub 2012 Jul 12.

Reference Type: RESULT

PMID: 22790642 (View on PubMed)

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 vitro. J Sex Med. 2011 Mar;8(3):696-704. doi: 10.1111/j.1743-6109.2010.02152.x. Epub 2010 Dec 22.

Reference Type: RESULT

PMID: 21176111 (View on PubMed)

Other Identifiers

FDAAA 801

Identifier Type: -

Identifier Source: org_study_id