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

Phase 4

Completed

Conditions: Obesity

Interventions: Drug: Placebo
Drug: Tadalafil

Registration Number: NCT02595684

Lead Sponsor: University of Guadalajara

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 18

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Calcined magnesia capsules
Tadalafil	Tadalafil	Tadalafil capsules

Primary Outcome Measures

Name	Time	Method
Fasting Glucose	Fasting glucose at Day 28	Fasting glucose will be evaluated at baseline and Day 28 with enzymatic-colorimetric.
Postprandial Glucose	Postprandial glucose at Day 28	Postprandial glucose will be evaluated at baseline and Day 28 after a oral glucose. tolerance test with enzymatic-colorimetric techniques.
First Phase of Insulin Secretion	First phase of insulin secretion at Day 28	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
Total Insulin Secretion	Total insulin secretion at Day 28	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
Insulin Sensitivity	Insulin sensitivity at Day 28	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
Area Under the Curve (AUC) Glucose	AUC at Day 28	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.
Area Under the Curve (AUC) Insulin	AUC at Day 28	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.

Secondary Outcome Measures

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