Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism

Study Overview
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Brief Summary
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Hypogonadism is a clinical condition that can be associated with obesity in man. Controversy exists regarding if its a condition that needs to be treated. The standard Testosterone Therapy is associated with increase in cardiovascular risks, according to some studies, and leads to infertility. The use of Clomiphene Citrate in this sub population of obese man as an alternative treatment option is not well studied. The aim of this protocol is to evaluate the cardiovascular risks, metabolic and hormonal parameters in a double blinded randomized placebo trial.

Detailed Description
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Hypogonadism (low testosterone level) in obese man is a clinical condition which treatment is controversial. Most of this controversy remains regarding the association between cardiovascular risk elevation and Testosterone replacement therapy in some studies. This protocol is a double blinded randomized placebo trial and 2 groups will be followed. The primary end-point of this research is the correlation between the serum testosterone and flow-mediated dilatation of the brachial artery (FMDAB), circulating levels of sICAM-1, sVCAM-1, E-selectin and progenitor endothelial cells. The secondary end-points include: (1) the evaluation of metabolic parameters: weight, abdominal circumference, glycaemia, total cholesterol, fractions and triglycerides, homeostasis model assessment index (HOMA) and bioelectrical impedance parameters; and (2) hormonal parameters: total testosterone levels, sex hormone-binding globulin (SHBG), Luteinizing Hormone (LH) , Follicle stimulating hormone (FSH) and Estradiol.

Official Title
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Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism: Metabolic and Cardiovascular Effects.

Conditions
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Obesity, Hypoandrogenism

Intervention / Treatment
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* Drug: Clomiphene Citrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ADAM questionnaire positive for 3 or more questions Total serum Testosterone lower than 300 ng/dL in two different occasions, within a 1-week minimum interval. This blood sample must be collected between 8 and 11 a.m. Low or Inappropriate normal serum Luteinizing hormone (LH) level ATP III Metabolic Syndrome Criteria Obesity - BMI over 30 kg/m2 Exclusion Criteria: Systemic illness, such Rheumatoid Arthritis, Cushing disease, liver insufficiency or renal insufficiency. -Use of certain medications (opiates, high-dose glucocorticoid therapy, methadone) Eating disorders Testicular volume below 4 mL Use of recreational drugs Excessive exercise practice Men in treatment for prostatic cancer Hyperprolactinaemia Hemochromatosis History of headache Systolic blood pressure lower than 100 mmHg Previous adverse reactions to nitrate compounds Diabetes over 10 years of diagnosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 78 patients were randomized (1:1) to receive Clomiphene Citrate (CC) 50 mg during 12 weeks or placebo (PLB). MAIN OUTCOME MEASURES: flow-mediated dilatation of the brachial artery (FMDAB), circulating levels of sICAM-1, sVCAM-1, E-selectin and progenitor endothelial cells. Secondary endpoints: Body mass index (BMI), abdominal circumference (AC), glycaemia, total cholesterol, fractions and triglycerides, HOMA-IR index, bioelectrical impedance parameters, Adam questionnaire and hormonal parameters (total testosterone levels, SHBG, LH, FSH and Estradiol).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One pill every other day during 12 weeks | Drug: Placebo<br>* 1 pill orally daily during 12 weeks<br>* Other names: Control;|
| Active Comparator: Clomiphene Citrate<br>Clomiphene citrate 50 mg orally daily (Serophene) during 12 weeks | Drug: Clomiphene Citrate<br>* 50 mg orally daily during 12 weeks<br>* Other names: Serophene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | Flow-mediated dilatation of the brachial artery (FMDAB): Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter. Icam, vcam and selectin Endothelial progenitor cels | baseline up to 12 weeks | 
| Total Testosterone | electrochemical luminescence analysis in blood sample | baseline up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, Male, Flow-mediated dilatation, Clomiphene citrate, sICAM-1, sVCAM-1, sE- Selectin, Endothelial function, Cardiovascular risk, Endocrine System Diseases, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Endothelial Progenitor Cells, Obesity, Testosterone