Clinical trial NCT02380755: Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism
Official title: Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism: Metabolic and Cardiovascular Effects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Hypoandrogenism
Keywords: 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
Infertility, Male
Endothelial Progenitor Cells
Obesity
Testosterone
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2015-03-05
Enrollment: 78
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Endothelial Function
timeFrame: baseline up to 12 weeks
measure: Total Testosterone
timeFrame: baseline up to 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Prédio dos ambulatórios HCFMUSP - PAMB
Study officials:
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Cintia Cercato, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculdade de Medicina da USP
name: Elaine Maria F Costa, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
References: