Effect of Tadalafil on Insulin Secretion and Insulin Sensitivity in Obese Men.

Study Overview
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Brief Summary
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Obesity is a chronic disease of multifactorial etiology that develops from the interaction of the influence of nutritive , metabolic , cellular and molecular psychological factors. Tadalafil is Is a drug inhibiting the enzyme phosphodiesterase-5 (PDE-5), responsible for inactivating the vasodilator nitric oxide. USING paragraph was mainly treat erectile dysfunction, and recently approved for the treatment of pulmonary hypertension , it is innovative because of its longer life means, provides efficacy after 36 hours and the highest selectivity. The aim of this study is to evaluate the effect of tadalafil on insulin sensitivity and insulin secretion in obese men. The investigators hypothesis is that the administration of tadalafil improve the insulin sensitivity and insulin secretion in obese men.

Detailed Description
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A randomized, double-blind, placebo-controlled clinical trial in 18 men aged between 30 and 50 years with obesity (BMI 30-39.9) according to the World Health Organization (WHO) criteria without treatment. They will be assigned randomly in two groups of 9 patients, each to receive 5 mg of tadalafil or placebo every day at night during 28 days. There will be evaluated Insulin secretion, both first phase of insulin secretion by Stumvoll Inex as well as Total Insulin Secretion by Area Under the Curve of glucose and insulin and Insulinogenic Index, and Insulin sensitivity by Matsuda index. Waist circumference, glucose and insulin levels, lipid profile and blood pressure are going to be load will be evaluated before and after intervention in both groups. Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. Will be considered statistical significance p ≤0.05. This protocol was approved by a local Ethics Committee and written informed consent will be obtained from all volunteers.

Official Title
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Effect of Tadalafil on Insulin Secretion and Insulin Sensitivity in Obese Men.

Conditions
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Obesity

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men Age: 30-50 years BMI: 30 to 39.9 kg/m² No Pharmacotherapy during the last 3 months Signature Consent under Information Exclusion Criteria: Cholesterol: ≥ 240 mg / dl Triglycerides: ≥ 400 mg / dl Fasting glucose: ≥ 126 mg / dl Diabetes mellitus. Hypertension Patients with renal, liver and / or thyroid disease Consumption of drugs with known effects on glucose or insulin metabolism. Use of cigar and / or drugs Hypersensitivity to tadalafil

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tadalafil<br>Tadalafil capsules | Drug: Tadalafil<br>* Tadalafil capsules: 5 mg, one per day, at night, during 28 days.<br>* Other names: Tadalafilo;|
| Placebo Comparator: Placebo<br>Calcined magnesia capsules | Drug: Placebo<br>* Calcined magnesia capsules: one per day, at night, during 28 days.<br>* Other names: Calcined magnesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Glucose | Fasting glucose will be evaluated at baseline and Day 28 with enzymatic-colorimetric. | Fasting glucose at Day 28 | 
| Postprandial Glucose | Postprandial glucose will be evaluated at baseline and Day 28 after a oral glucose. tolerance test with enzymatic-colorimetric techniques. | Postprandial glucose at Day 28 | 
| First Phase of Insulin Secretion | First phase of insulin secretion will be calculated at baseline and Day 28 with Stumvoll Index. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion | First phase of insulin secretion at Day 28 | 
| Total Insulin Secretion | Total insulin secretion will be calculated at baseline and Day 28 with Insulinogenic Index. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔAUC insulin/ΔAUC glucose), the entered values reflect the total insulin secretion | Total insulin secretion at Day 28 | 
| Insulin Sensitivity | Insulin sensitivity will be calculated at baseline and Day 28 with Matsuda Index. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index [10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)]. The entered values reflect the insulin sensitivity | Insulin sensitivity at Day 28 | 
| Area Under the Curve (AUC) Glucose | Area under the curve of glucose measured at baseline and Day 28. The area under the curve (AUC) of glucose, (0.5 * glucose (G) 0´ + (G 30´+G 60´ + G 90´) + 0.5 * G 120´) * 30; has been widely used for calculating the glycemic index and for evaluating the efficacy of medications for postprandial hyperglycemia. | AUC at Day 28 | 
| Area Under the Curve (AUC) Insulin | Area under the curve of insulin measured at baseline and Day 28. The Area Under the Curve (AUC) of insulin, (0.5 * Insulin (I) 0´ + (I 30´+I 60´ + I 90´) + 0.5 * I 120´) * 30; has been widely used for calculating the glycemic index and for evaluating the efficacy of medications for postprandial hyperinsulinemia. | AUC at Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Weight | The body weight will be measured at baseline and Day 28 by Electrical bioimpedance. | Body Weight at Day 28 | 
| Body Mass Index | The Body Mass Index will be measured at baseline and Day 28 by Quetelet Index Formula. | Body Mass Index at Day 28 | 
| Waist Circumference | Waist circumference was evaluated at baseline and at Day 28 with a flexible tape. | Waist circumference at Day 28 | 
| Triglycerides | Triglycerides levels will be evaluated at baseline and Day 28 with enzymatic-colorimetric techniques. | Triglycerides levels at Day 28 | 
| Total Cholesterol | Total cholesterol levels will be evaluated at baseline and Day 28 with enzymatic-colorimetric techniques. | Total cholesterol levels at Day 28 | 
| High Density Lipoprotein Cholesterol (HDL-c) | High density lipoprotein cholesterol (HDL-c) levels will be evaluated at baseline and Day 28 with enzymatic-colorimetric techniques. | HDL-c levels at Day 28 | 
| Low Density Lipoprotein Cholesterol (LDL-c) | Low density lipoprotein cholesterol (LDL-c) levels will be evaluated at baseline and Day 28 with Friedewald formula. | LDL-c levels at Day 28 | 
| Systolic Blood Pressure | The systolic blood pressure was evaluated at baseline and Day 28 with a digital sphygmomanometer. | Systolic Blood Pressure at Day 28 | 
| Diastolic Blood Pressure |  | Diastolic Blood Pressure at Day 28 | 
| Body Fat | The body fat will be measured at baseline and Day 28 by Electrical bioimpedance in % | Body fat at Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Tadalfil, Insulin secretion, Insulin sensitivity