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

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

Status and phase: Completed; Phase 3

Conditions: Obesity; Hypogonadism

Treatments: Drug: Testosterone Undecanoate; Drug: Metformin; Drug: Placebo; Drug: Metformin + Testosterone Undecanoate

Study type: Interventional

Funder types: Other

Identifiers

NCT02514629

CMCS240281

Details and patient eligibility

About

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

Enrollment: 107 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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107 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo for 52 weeks

Treatment:

Drug: Placebo

Metformin

Experimental group

Description:

Metformin 850 mg tablets twice daily for 52 weeks

Treatment:

Drug: Metformin

Testosterone

Experimental group

Description:

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

Treatment:

Drug: Testosterone Undecanoate

Metformin + Testosterone

Experimental group

Description:

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

Treatment:

Drug: Metformin + Testosterone Undecanoate