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

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.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Tadalafil; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44140
      • Instituto de Terapéutica Experimental y Clínica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tadalafil; Tadalafil capsules	Drug: Tadalafil; Tadalafil capsules: 5 mg, one per day, at night, during 28 days.; Other Names: Tadalafilo
Placebo Comparator: Placebo; Calcined magnesia capsules	Drug: Placebo; Calcined magnesia capsules: one per day, at night, during 28 days.; Other Names: Calcined magnesia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: Manuel González-Ortíz, PhD, University of Guadalajara

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: November 2, 2015
• First Posted (Estimate): November 3, 2015

Study Record Updates

• Last Update Posted (Actual): October 9, 2020
• Last Update Submitted That Met QC Criteria: September 16, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Obesity; Insulin sensitivity; Insulin secretion; Tadalfil
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: TADALAFIL-OB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No