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Testosterone, Metformin, or Both, for Hypogonadism in Obese Males

Primary Purpose

Hypogonadism, Obesity

Status

Completed

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Placebo

Metformin

Testosterone Undecanoate

Metformin + Testosterone Undecanoate

About this trial

This is an interventional treatment trial for Hypogonadism focused on measuring Hypogonadism, Obesity, Erectile Dysfunction, Testosterone, Metformin, Weight Loss, Insulin Resistance

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Men aged 18 to 50 years.
BMI > or = 30 kg/m2.
Total testosterone levels <2.3 ng/ml (<8 nmol/l) or testosterone levels 2.3-3.49 ng/ml (8-12 nmol/l) and free testosterone levels <70 pg/ml.
LH levels <7.7 mIU / ml.
No evidence of any other pituitary hormone disruption in morning blood sample (normal concentrations of TSH, FT4, Prolactin, ACTH, cortisol and IGF-1
Being able to provide informed consent before randomization and agree to comply with all the procedures included in the protocol.

Exclusion Criteria:

Intolerance/allergy to metformin or testosterone undecanoate.
Previous diagnosis of diabetes mellitus (HbA1c> 6.5% or fasting glucose> 126 mg/dl or glucose> 200 mg/dl after an oral glucose tolerance test)
Treatment with oral hypoglycemic agents, insulin or GLP-1 analogs.
Poor kidney function: serum creatinine> 2.0 mg / dl.
Previous history of prostate cancer or breast cancer.
Active cancer of any kind.
History of liver tumor or acute or chronic liver disease with impaired liver function: total bilirubin> 2.0 mg / dl or GOT levels three times the upper limit of normal.
Central hypogonadism of organic cause
Use in the past 12 months of any drug that affects the pituitary-gonadal axis.
Use of oral testosterone, oral or transdermal within 2 weeks prior to study entry, or any testosterone ester in the last 6 weeks or testosterone undecanoate injection in the 6 months prior to study entry.
Uncontrolled hypertension (SBP> 160 mmHg or DBP> 100 mmHg) despite adequate antihypertensive therapy.
HIV infection or known active infection with HBV or HCV.
Thrombotic or embolic disease.
Heart disease, kidney or liver disease.
Epilepsy or migraine not adequately controlled with treatment.
Hematocrit> 50% in the screening.
PSA> 4 ng / ml.
Severe benign prostatic hypertrophy with an IPSS scale score over 19.
Evidence of drug or alcohol abuse (> 50 g alcohol / day)
Hematological diseases that produce increased risk of bleeding after intramuscular injection.
Serious underlying disease that might affect the patient's ability to participate in the study (eg ongoing infection, gastric ulcers, active autoimmune disease).
Reduced life expectancy (<12 months) by the presence of comorbidities or advanced terminals.
Participation in another clinical trial within 30 days before study entry.
Previous diagnosis of hemochromatosis
Treatment with phosphodiesterase-5 inhibitors: sildenafil, tadalafil or vardenafil

Sites / Locations

Hospital Uiversitario Virgen de la Victoria

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Metformin

Testosterone

Metformin + Testosterone

Arm Description

Placebo for 52 weeks

Metformin 850 mg tablets twice daily for 52 weeks

Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks

Metformin 850 mg tablets twice daily + Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks

Outcomes

Primary Outcome Measures

Change in Insulin Resistance

Insulin resistance will be measured using Homeostasis Model of Assessment for Insulin Resistance index (HOMA-IR index) HOMA-IR=FINS*FGLU/22.5

Secondary Outcome Measures

Change in Body Weight

Body weight will be measured on a Tanita Multi-Frequency Body Composition Analyzer MC-180MA (Tanita Corporation, Tokyo, Japan) to assess change in body weight over the 52-week intervention period.

Change in Erectile Dysfunction

Changes in Erectile Dysfunction will be evaluated with the International Index of Erectile Function (IIEF-5) questionnaire

Change in the Aging Male Symptom (AMS) Scale

Change from baseline on the total score of the AMS rating scale

Change in the Androgen Deficiency in the Aging Male (ADAM) Questionnaire

Change from baseline on the ADAM Questionnaire

Change in Testosterone Levels (Total and Free)

The change from baseline to week 52 in free testosterone and total testosterone levels will be assessed

Change in Body Composition (Fat and Lean Mass)

Body Composition will be measured on a Tanita Multi-Frequency Body Composition Analyzer MC-180MA (Tanita Corporation, Tokyo, Japan) to assess changes in body composition (fat mass, lean mass, total body water) over the 52-week intervention period.

Change in Biochemical Markers of Bone Turnover

Change in Bone turnover, measured by serum procollagen type I N-terminal propeptide (PINP) and Beta-CrossLaps (β-CTx)

Change in Metabolic Hormones

Changes in Leptin, adiponectin, betatrophin and kisspeptin levels

Full Information

NCT ID

NCT02514629

First Posted

July 15, 2015

Last Updated

March 29, 2017

Sponsor

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

1. Study Identification

Unique Protocol Identification Number

NCT02514629

Brief Title

Testosterone, Metformin, or Both, for Hypogonadism in Obese Males

Official Title

Randomized, Double-blind, Parallel, Placebo-controlled, Clinical Trial to Assess the Efficacy of Testosterone, Metformin, or Both, for the Treatment of Obesity-induced Male Hypogonadism

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

July 4, 2013 (undefined)

Primary Completion Date

July 12, 2016 (Actual)

Study Completion Date

July 12, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to examine the effects of metformin, testosterone, or both, in males with obesity-related hypogonadism. This study will evaluate changes in insulin resistance, weight loss, body composition, testosterone levels,quality of life and erectile dysfunction. Obese men will receive diet and physical activity counselling, and be randomised to either testosterone, metformin, a combination of both or placebo

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypogonadism, Obesity

Keywords

Hypogonadism, Obesity, Erectile Dysfunction, Testosterone, Metformin, Weight Loss, Insulin Resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

107 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo for 52 weeks

Arm Title

Metformin

Arm Type

Experimental

Arm Description

Metformin 850 mg tablets twice daily for 52 weeks

Arm Title

Testosterone

Arm Type

Experimental

Arm Description

Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks

Arm Title

Metformin + Testosterone

Arm Type

Experimental

Arm Description

Metformin 850 mg tablets twice daily + Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Glucophage, Dianben

Intervention Type

Drug

Intervention Name(s)

Testosterone Undecanoate

Other Intervention Name(s)

Nebido, Reandron

Intervention Type

Drug

Intervention Name(s)

Metformin + Testosterone Undecanoate

Primary Outcome Measure Information:

Title

Change in Insulin Resistance

Description

Insulin resistance will be measured using Homeostasis Model of Assessment for Insulin Resistance index (HOMA-IR index) HOMA-IR=FINS*FGLU/22.5

Time Frame

Basal-52 weeks

Secondary Outcome Measure Information:

Title

Change in Body Weight

Description

Body weight will be measured on a Tanita Multi-Frequency Body Composition Analyzer MC-180MA (Tanita Corporation, Tokyo, Japan) to assess change in body weight over the 52-week intervention period.

Time Frame

Basal-52 weeks

Title

Change in Erectile Dysfunction

Description

Changes in Erectile Dysfunction will be evaluated with the International Index of Erectile Function (IIEF-5) questionnaire

Time Frame

Basal-52 weeks

Title

Change in the Aging Male Symptom (AMS) Scale

Description

Change from baseline on the total score of the AMS rating scale

Time Frame

Basal-52 weeks

Title

Change in the Androgen Deficiency in the Aging Male (ADAM) Questionnaire

Description

Change from baseline on the ADAM Questionnaire

Time Frame

Basal-52 weeks

Title

Change in Testosterone Levels (Total and Free)

Description

The change from baseline to week 52 in free testosterone and total testosterone levels will be assessed

Time Frame

Basal-52 weeks

Title

Change in Body Composition (Fat and Lean Mass)

Description

Time Frame

Basal-52 weeks

Title

Change in Biochemical Markers of Bone Turnover

Description

Change in Bone turnover, measured by serum procollagen type I N-terminal propeptide (PINP) and Beta-CrossLaps (β-CTx)

Time Frame

Basal-52 weeks

Title

Change in Metabolic Hormones

Description

Changes in Leptin, adiponectin, betatrophin and kisspeptin levels

Time Frame

Basal-52 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men aged 18 to 50 years. BMI > or = 30 kg/m2. Total testosterone levels <2.3 ng/ml (<8 nmol/l) or testosterone levels 2.3-3.49 ng/ml (8-12 nmol/l) and free testosterone levels <70 pg/ml. LH levels <7.7 mIU / ml. No evidence of any other pituitary hormone disruption in morning blood sample (normal concentrations of TSH, FT4, Prolactin, ACTH, cortisol and IGF-1 Being able to provide informed consent before randomization and agree to comply with all the procedures included in the protocol. Exclusion Criteria: Intolerance/allergy to metformin or testosterone undecanoate. Previous diagnosis of diabetes mellitus (HbA1c> 6.5% or fasting glucose> 126 mg/dl or glucose> 200 mg/dl after an oral glucose tolerance test) Treatment with oral hypoglycemic agents, insulin or GLP-1 analogs. Poor kidney function: serum creatinine> 2.0 mg / dl. Previous history of prostate cancer or breast cancer. Active cancer of any kind. History of liver tumor or acute or chronic liver disease with impaired liver function: total bilirubin> 2.0 mg / dl or GOT levels three times the upper limit of normal. Central hypogonadism of organic cause Use in the past 12 months of any drug that affects the pituitary-gonadal axis. Use of oral testosterone, oral or transdermal within 2 weeks prior to study entry, or any testosterone ester in the last 6 weeks or testosterone undecanoate injection in the 6 months prior to study entry. Uncontrolled hypertension (SBP> 160 mmHg or DBP> 100 mmHg) despite adequate antihypertensive therapy. HIV infection or known active infection with HBV or HCV. Thrombotic or embolic disease. Heart disease, kidney or liver disease. Epilepsy or migraine not adequately controlled with treatment. Hematocrit> 50% in the screening. PSA> 4 ng / ml. Severe benign prostatic hypertrophy with an IPSS scale score over 19. Evidence of drug or alcohol abuse (> 50 g alcohol / day) Hematological diseases that produce increased risk of bleeding after intramuscular injection. Serious underlying disease that might affect the patient's ability to participate in the study (eg ongoing infection, gastric ulcers, active autoimmune disease). Reduced life expectancy (<12 months) by the presence of comorbidities or advanced terminals. Participation in another clinical trial within 30 days before study entry. Previous diagnosis of hemochromatosis Treatment with phosphodiesterase-5 inhibitors: sildenafil, tadalafil or vardenafil

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jose Carlos Fernandez-Garcia, MD

Organizational Affiliation

Hospital Universitario Virgen de la Victoria. Malaga

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Uiversitario Virgen de la Victoria

City

Malaga

ZIP/Postal Code

29010

Country

Spain

12. IPD Sharing Statement

Learn more about this trial

Testosterone, Metformin, or Both, for Hypogonadism in Obese Males

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