Clomid in Men With Low Testosterone With and Without Prior Treatment

Study Overview
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Brief Summary
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This study aims to explore whether men with low testosterone levels, due to altered brain regulation of male hormone function, who have been previously treated with testosterone, respond as well as men who have not been so treated to clomiphene citrate, an agent commonly used for female infertility that has been shown to improve male hormone secretion in some cases.

Detailed Description
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Clomiphene, an oral FDA-approved agent for female infertility has been shown to normalize testosterone levels in men with hypogonadotropic hypogonadism. It appears to be safe and well tolerated. This study will compare testosterone responses to clomiphene citrate in male veterans with hypothalamic hypogonadism naïve to treatment with responses of similar patients already receiving treatment with injectable or transdermal testosterone. This is an open-label, prospective, interventional trial to be conducted in an outpatient specialty care setting. We will randomize 64 hypogonadal male veterans evenly divided between naive and previous treatment and treat for 8 weeks with clomid, increasing the initial dose of 25 mg to 50 mg/day in those who fail to achieve target testosterone level (450 ng/dl) after the first 3 weeks. Endpoint measurements performed in the Phoenix VA Health Care System (PVAHCS) clinical laboratory will be total testosterone as well as bioavailable testosterone and sex hormone binding globulin. Total testosterone level at 8 weeks of treatment will be reported as the primary endpoint. Safety measures (CBC,liver functions, PSA) will be assessed at 8 weeks as well. This study will help serve as a guide for design of future studies of clomiphene in hypogonadal men.

Official Title
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A Comparison of Clomiphene Citrate Responses in Men With Hypothalamic Hypogonadism naïve to, and Previously Treated With, Testosterone

Conditions
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Hypogonadism, Male

Intervention / Treatment
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* Drug: Clomiphene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient or eligible for care at Phoenix VA Health Care System Male ages 30-70 years testosterone level below 250 ng/dl before treatment able to provide informed written consent Exclusion Criteria: evidence of pituitary tumor >1mm by MRI or CAT scan chronic illness (renal, cardiac, liver failure) Prostate specific antigen (PSA) >4.0 ng/ml history of prostate, breast, or testicular cancer eye disease compromising vision (e.g. cataracts)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No previous male hormone treatment<br>Clomiphene | Drug: Clomiphene<br>* Start with 25 mg and escalate to 50 mg in men not achieving goal for serum testosterone after 3 weeks<br>* Other names: Clomiphene citrate;|
| Active Comparator: Previously treated with testosterone<br>Clomiphene | Drug: Clomiphene<br>* Start with 25 mg and escalate to 50 mg in men not achieving goal for serum testosterone after 3 weeks<br>* Other names: Clomiphene citrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total serum testosterone | laboratory measurement by standard immunometric method | at the end of 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioavailable testosterone | Non-SHBG bound testosterone by ammonium sulfate precipitation method | at the end of 8 weeks of treatment | 
| Serum sex hormone binding globulin (SHBG)level | Laboratory measurement of SHBG by standard immunometric technique | at the end of 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, hypogonadism, pituitary