Obesity
Conditions
Keywords
Obesity, Tadalfil, Insulin secretion, Insulin sensitivity
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.
Interventions
DRUGTadalafil
Tadalafil capsules: 5 mg, one per day, at night, during 28 days.
DRUGPlacebo
Calcined magnesia capsules: one per day, at night, during 28 days.
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
30 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | Systolic Blood Pressure at Day 28 | The systolic blood pressure was evaluated at baseline and Day 28 with a digital sphygmomanometer. |
| Body Weight | Body Weight at Day 28 | The body weight will be measured at baseline and Day 28 by Electrical bioimpedance. |
| Body Fat | Body fat at Day 28 | The body fat will be measured at baseline and Day 28 by Electrical bioimpedance in % |
| Diastolic Blood Pressure | Diastolic Blood Pressure at Day 28 | — |
| 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. |
| Waist Circumference | Waist circumference at Day 28 | Waist circumference was evaluated at baseline and at Day 28 with a flexible tape. |
| 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. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tadalafil Tadalafil capsules
Tadalafil: Tadalafil capsules: 5 mg, one per day, at night, during 28 days. | 9 |
| Placebo Calcined magnesia capsules
Placebo: Calcined magnesia capsules: one per day, at night, during 28 days. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Placebo | Tadalafil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 9 Participants | 18 Participants |
| Age, Continuous | 38.4 years STANDARD_DEVIATION 6.4 | 40.2 years STANDARD_DEVIATION 7.9 | 39.3 years STANDARD_DEVIATION 7.2 |
| Area under the curve (AUC) glucose | 513 mmol*h/L STANDARD_DEVIATION 146 | 508 mmol*h/L STANDARD_DEVIATION 87 | 511 mmol*h/L STANDARD_DEVIATION 117 |
| Area under the curve (AUC) insulin | 326 pmol*h/L STANDARD_DEVIATION 181 | 285 pmol*h/L STANDARD_DEVIATION 114 | 307 pmol*h/L STANDARD_DEVIATION 146 |
| Body Fat | 31.0 % STANDARD_DEVIATION 2.8 | 33.3 % STANDARD_DEVIATION 6.6 | 32.1 % STANDARD_DEVIATION 4.8 |
| Body Mass Index | 33.3 kg/m^2 STANDARD_DEVIATION 3.7 | 33.4 kg/m^2 STANDARD_DEVIATION 3.3 | 33.35 kg/m^2 STANDARD_DEVIATION 3.5 |
| Body Weight | 98.9 kg STANDARD_DEVIATION 10.4 | 98.2 kg STANDARD_DEVIATION 14.4 | 98.55 kg STANDARD_DEVIATION 12.4 |
| Diastolic Blood Pressure | 76 mmHg STANDARD_DEVIATION 8 | 81 mmHg STANDARD_DEVIATION 7 | 78.5 mmHg STANDARD_DEVIATION 7.5 |
| Fasting Glucose | 4.8 mmol/L STANDARD_DEVIATION 0.7 | 4.9 mmol/L STANDARD_DEVIATION 0.4 | 4.85 mmol/L STANDARD_DEVIATION 0.55 |
| First Phase of Insulin | 1135 index STANDARD_DEVIATION 598 | 1332 index STANDARD_DEVIATION 487 | 1233.5 index STANDARD_DEVIATION 542.5 |
| High Density LIpoprotein cholesterol (HDL-c) | 1.0 mmol/L STANDARD_DEVIATION 0.2 | 1.1 mmol/L STANDARD_DEVIATION 0.3 | 1.05 mmol/L STANDARD_DEVIATION 0.25 |
| Insulin Sensitivity | 5.0 index STANDARD_DEVIATION 2.9 | 4.6 index STANDARD_DEVIATION 1.2 | 4.8 index STANDARD_DEVIATION 2.05 |
| Low density lipoprotein cholesterol (LDL-c) | 2.6 mmol/L STANDARD_DEVIATION 0.5 | 2.7 mmol/L STANDARD_DEVIATION 0.7 | 2.65 mmol/L STANDARD_DEVIATION 0.6 |
| Postprandial Glucose | 5.4 mmol/L STANDARD_DEVIATION 1.3 | 6.6 mmol/L STANDARD_DEVIATION 1.9 | 6 mmol/L STANDARD_DEVIATION 1.6 |
| Region of Enrollment Mexico | 9 participants | 9 participants | 18 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
| Systolic Blood Pressure | 120 mmHg STANDARD_DEVIATION 10 | 120 mmHg STANDARD_DEVIATION 8 | 120 mmHg STANDARD_DEVIATION 9 |
| Total Cholesterol | 4.5 mmol/L STANDARD_DEVIATION 0.8 | 4.6 mmol/L STANDARD_DEVIATION 1.2 | 4.55 mmol/L STANDARD_DEVIATION 1 |
| Total Insulin Secretion | 0.45 index STANDARD_DEVIATION 0.21 | 0.82 index STANDARD_DEVIATION 0.45 | 0.64 index STANDARD_DEVIATION 0.33 |
| Triglycerides | 1.9 mmol/L STANDARD_DEVIATION 0.9 | 1.9 mmol/L STANDARD_DEVIATION 1 | 1.9 mmol/L STANDARD_DEVIATION 0.95 |
| Waist Circumference | 110 cm STANDARD_DEVIATION 13 | 111 cm STANDARD_DEVIATION 9 | 110.5 cm STANDARD_DEVIATION 11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 9 | 4 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
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.
Time frame: AUC at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Area Under the Curve (AUC) Glucose | 503 mmol*h/L | Standard Deviation 137 |
| Placebo | Area Under the Curve (AUC) Glucose | 522 mmol*h/L | Standard Deviation 135 |
p-value: 0.859Wilcoxon (Mann-Whitney)
p-value: 0.767Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: AUC at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Area Under the Curve (AUC) Insulin | 291 pmol*h/L | Standard Deviation 160 |
| Placebo | Area Under the Curve (AUC) Insulin | 262 pmol*h/L | Standard Deviation 110 |
p-value: 0.374Wilcoxon (Mann-Whitney)
p-value: 0.953Wilcoxon (Mann-Whitney)
Primary
Fasting Glucose
Fasting glucose will be evaluated at baseline and Day 28 with enzymatic-colorimetric.
Time frame: Fasting glucose at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Fasting Glucose | 4.8 mmol/L | Standard Deviation 0.6 |
| Placebo | Fasting Glucose | 5.0 mmol/L | Standard Deviation 0.5 |
p-value: 0.327Wilcoxon (Mann-Whitney)
p-value: 0.635Wilcoxon (Mann-Whitney)
Primary
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
Time frame: First phase of insulin secretion at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | First Phase of Insulin Secretion | 1602 index | Standard Deviation 800 |
| Placebo | First Phase of Insulin Secretion | 1194 index | Standard Deviation 490 |
p-value: 515Wilcoxon (Mann-Whitney)
p-value: 0.953Wilcoxon (Mann-Whitney)
Primary
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
Time frame: Insulin sensitivity at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Insulin Sensitivity | 4.8 index | Standard Deviation 3.1 |
| Placebo | Insulin Sensitivity | 4.9 index | Standard Deviation 2.5 |
p-value: 0.767Wilcoxon (Mann-Whitney)
p-value: 0.779Wilcoxon (Mann-Whitney)
Primary
Postprandial Glucose
Postprandial glucose will be evaluated at baseline and Day 28 after a oral glucose. tolerance test with enzymatic-colorimetric techniques.
Time frame: Postprandial glucose at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Postprandial Glucose | 6.3 mmol/L | Standard Deviation 2.1 |
| Placebo | Postprandial Glucose | 6.5 mmol/L | Standard Deviation 2.3 |
p-value: 0.38Wilcoxon (Mann-Whitney)
p-value: 0.441Wilcoxon (Mann-Whitney)
Primary
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
Time frame: Total insulin secretion at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Total Insulin Secretion | 0.52 index | Standard Deviation 0.29 |
| Placebo | Total Insulin Secretion | 0.61 index | Standard Deviation 0.27 |
p-value: 0.314Wilcoxon (Mann-Whitney)
p-value: 0.594Wilcoxon (Mann-Whitney)
Secondary
Body Fat
The body fat will be measured at baseline and Day 28 by Electrical bioimpedance in %
Time frame: Body fat at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Body Fat | 33.7 percentage of fat | Standard Deviation 3.3 |
| Placebo | Body Fat | 33.1 percentage of fat | Standard Deviation 3.7 |
p-value: 0.092Wilcoxon (Mann-Whitney)
p-value: 0.374Wilcoxon (Mann-Whitney)
Secondary
Body Mass Index
The Body Mass Index will be measured at baseline and Day 28 by Quetelet Index Formula.
Time frame: Body Mass Index at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Body Mass Index | 33.7 kg/m^2 | Standard Deviation 3.3 |
| Placebo | Body Mass Index | 33.1 kg/m^2 | Standard Deviation 3.2 |
p-value: 0.594Wilcoxon (Mann-Whitney)
p-value: 0.086Wilcoxon (Mann-Whitney)
Secondary
Body Weight
The body weight will be measured at baseline and Day 28 by Electrical bioimpedance.
Time frame: Body Weight at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Body Weight | 99.1 kg | Standard Deviation 14.4 |
| Placebo | Body Weight | 98.2 kg | Standard Deviation 9 |
p-value: 0.594Wilcoxon (Mann-Whitney)
p-value: 0.085Wilcoxon (Mann-Whitney)
Secondary
Diastolic Blood Pressure
Time frame: Diastolic Blood Pressure at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Diastolic Blood Pressure | 77 mmHg | Standard Deviation 6 |
| Placebo | Diastolic Blood Pressure | 73 mmHg | Standard Deviation 7 |
p-value: 0.128Wilcoxon (Mann-Whitney)
p-value: 0.108Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: HDL-c levels at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | High Density Lipoprotein Cholesterol (HDL-c) | 1.1 mmol/L | Standard Deviation 0.2 |
| Placebo | High Density Lipoprotein Cholesterol (HDL-c) | 1.1 mmol/L | Standard Deviation 0.2 |
p-value: 0.722Wilcoxon (Mann-Whitney)
p-value: 0.953Wilcoxon (Mann-Whitney)
Secondary
Low Density Lipoprotein Cholesterol (LDL-c)
Low density lipoprotein cholesterol (LDL-c) levels will be evaluated at baseline and Day 28 with Friedewald formula.
Time frame: LDL-c levels at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Low Density Lipoprotein Cholesterol (LDL-c) | 2.3 mmol/L | Standard Deviation 0.5 |
| Placebo | Low Density Lipoprotein Cholesterol (LDL-c) | 2.2 mmol/L | Standard Deviation 0.8 |
p-value: 0.26Wilcoxon (Mann-Whitney)
p-value: 0.314Wilcoxon (Mann-Whitney)
Secondary
Systolic Blood Pressure
The systolic blood pressure was evaluated at baseline and Day 28 with a digital sphygmomanometer.
Time frame: Systolic Blood Pressure at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Systolic Blood Pressure | 120 mmHg | Standard Deviation 6 |
| Placebo | Systolic Blood Pressure | 115 mmHg | Standard Deviation 8 |
p-value: 0.058Wilcoxon (Mann-Whitney)
p-value: 0.952Wilcoxon (Mann-Whitney)
Secondary
Total Cholesterol
Total cholesterol levels will be evaluated at baseline and Day 28 with enzymatic-colorimetric techniques.
Time frame: Total cholesterol levels at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Total Cholesterol | 4.4 mmol/L | Standard Deviation 0.9 |
| Placebo | Total Cholesterol | 4.3 mmol/L | Standard Deviation 1.3 |
p-value: 0.859Wilcoxon (Mann-Whitney)
p-value: 0.374Wilcoxon (Mann-Whitney)
Secondary
Triglycerides
Triglycerides levels will be evaluated at baseline and Day 28 with enzymatic-colorimetric techniques.
Time frame: Triglycerides levels at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Triglycerides | 2.3 mmol/L | Standard Deviation 1.9 |
| Placebo | Triglycerides | 2.4 mmol/L | Standard Deviation 2 |
p-value: 0.374Wilcoxon (Mann-Whitney)
p-value: 0.263Wilcoxon (Mann-Whitney)
Secondary
Waist Circumference
Waist circumference was evaluated at baseline and at Day 28 with a flexible tape.
Time frame: Waist circumference at Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tadalafil | Waist Circumference | 112 cm | Standard Deviation 9 |
| Placebo | Waist Circumference | 112 cm | Standard Deviation 13 |
p-value: 0.285Wilcoxon (Mann-Whitney)
p-value: 0.854Wilcoxon (Mann-Whitney)