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

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

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

Study Overview

• Status: Completed
• Conditions: Obesity; Hypogonadism
• Intervention / Treatment: Drug: Placebo; Drug: Metformin; Drug: Testosterone Undecanoate; Drug: Metformin + Testosterone Undecanoate

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Malaga, Spain, 29010
    • Hospital Uiversitario Virgen de la Victoria

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo for 52 weeks	Drug: Placebo
Experimental: Metformin; Metformin 850 mg tablets twice daily for 52 weeks	Drug: Metformin; Other Names: Glucophage; Dianben
Experimental: Testosterone; Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks	Drug: Testosterone Undecanoate; Other Names: Nebido; Reandron
Experimental: Metformin + Testosterone; Metformin 850 mg tablets twice daily + Testosterone Undecanoate 1000 mg/4ml im injection each 12 weeks for 52 weeks	Drug: Metformin + Testosterone Undecanoate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Basal-52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Basal-52 weeks
Change in Erectile Dysfunction	Changes in Erectile Dysfunction will be evaluated with the International Index of Erectile Function (IIEF-5) questionnaire	Basal-52 weeks
Change in the Aging Male Symptom (AMS) Scale	Change from baseline on the total score of the AMS rating scale	Basal-52 weeks
Change in the Androgen Deficiency in the Aging Male (ADAM) Questionnaire	Change from baseline on the ADAM Questionnaire	Basal-52 weeks
Change in Testosterone Levels (Total and Free)	The change from baseline to week 52 in free testosterone and total testosterone levels will be assessed	Basal-52 weeks
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.	Basal-52 weeks
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)	Basal-52 weeks
Change in Metabolic Hormones	Changes in Leptin, adiponectin, betatrophin and kisspeptin levels	Basal-52 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Investigators: Principal Investigator: Jose Carlos Fernandez-Garcia, MD, Hospital Universitario Virgen de la Victoria. Málaga

Study record dates

Study Major Dates

• Study Start: July 4, 2013
• Primary Completion (Actual): July 12, 2016
• Study Completion (Actual): July 12, 2016

Study Registration Dates

• First Submitted: July 15, 2015
• First Submitted That Met QC Criteria: July 30, 2015
• First Posted (Estimate): August 4, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Obesity; Insulin Resistance; Erectile Dysfunction; Metformin; Weight Loss; Hypogonadism; Testosterone
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypogonadism; Hypoglycemic Agents; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Metformin; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: CMCS240281