Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism
Primary Purpose
Obesity, Hypoandrogenism
Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Clomiphene Citrate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obesity focused on measuring 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
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
Sites / Locations
- Prédio dos ambulatórios HCFMUSP - PAMB
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Clomiphene Citrate
Arm Description
One pill every other day during 12 weeks
Clomiphene citrate 50 mg orally daily (Serophene) during 12 weeks
Outcomes
Primary Outcome Measures
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
Total Testosterone
electrochemical luminescence analysis in blood sample
Secondary Outcome Measures
Full Information
NCT ID
NCT02380755
First Posted
March 1, 2015
Last Updated
December 23, 2017
Sponsor
University of Sao Paulo
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo
1. Study Identification
Unique Protocol Identification Number
NCT02380755
Brief Title
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
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigator
Masking Description
randomized, double blinded, placebo-controlled, parallel group, single-center study
Allocation
Randomized
Enrollment
78 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
One pill every other day during 12 weeks
Arm Title
Clomiphene Citrate
Arm Type
Active Comparator
Arm Description
Clomiphene citrate 50 mg orally daily (Serophene) during 12 weeks
Intervention Type
Drug
Intervention Name(s)
Clomiphene Citrate
Other Intervention Name(s)
Serophene
Intervention Description
50 mg orally daily during 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
1 pill orally daily during 12 weeks
Primary Outcome Measure Information:
Title
Endothelial Function
Description
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
Time Frame
baseline up to 12 weeks
Title
Total Testosterone
Description
electrochemical luminescence analysis in blood sample
Time Frame
baseline up to 12 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cintia Cercato, MD
Organizational Affiliation
Hospital das Clínicas da Faculdade de Medicina da USP
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elaine Maria F Costa, Prof, PhD
Organizational Affiliation
Faculdade de Medicina da USP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prédio dos ambulatórios HCFMUSP - PAMB
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
12. IPD Sharing Statement
Learn more about this trial
Clomiphene Citrate for the Treatment of Obesity Related Male Hypogonadism
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