Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism

Sponsor

University of Sao Paulo (Other)

Overall Status

Completed

CT.gov ID

NCT02380755

Collaborator

Fundação de Amparo à Pesquisa do Estado de São Paulo (Other)

Enrollment

Location

Arms

21.1

Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity Hypoandrogenism	Drug: Clomiphene Citrate Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

78 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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).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 (Participant, Care Provider, Investigator)

Masking Description:

randomized, double blinded, placebo-controlled, parallel group, single-center study

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Jan 1, 2017

Actual Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo One pill every other day during 12 weeks	Drug: Placebo 1 pill orally daily during 12 weeks Other Names: Control
Active Comparator: Clomiphene Citrate Clomiphene citrate 50 mg orally daily (Serophene) during 12 weeks	Drug: Clomiphene Citrate 50 mg orally daily during 12 weeks Other Names: Serophene

Arm

Intervention/Treatment

Placebo Comparator: Placebo

One pill every other day during 12 weeks

Drug: Placebo

1 pill orally daily during 12 weeks

Other Names:

Control

Active Comparator: Clomiphene Citrate

Clomiphene citrate 50 mg orally daily (Serophene) during 12 weeks

Drug: Clomiphene Citrate

50 mg orally daily during 12 weeks

Other Names:

Serophene

Outcome Measures

Primary Outcome Measures

Endothelial Function [baseline up to 12 weeks]
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
Total Testosterone [baseline up to 12 weeks]
electrochemical luminescence analysis in blood sample

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prédio dos ambulatórios HCFMUSP - PAMB	Sao Paulo		Brazil	05403-000

Sponsors and Collaborators

University of Sao Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators

Principal Investigator: Cintia Cercato, MD, Hospital das Clínicas da Faculdade de Medicina da USP
Principal Investigator: Elaine Maria F Costa, Prof, PhD, Faculdade de Medicina da USP