ITT-5 Mechanisms of Spermatogenesis in Man

Study Overview
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Brief Summary
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The purpose of this investigational drug study is to determine how much male hormone, testosterone, is needed to maintain sperm production in the testis.

Detailed Description
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This is a nine-month research study examining the effects on androgen treatment on sperm production in healthy men. There are three phase to the study, a 2-month screening phase, 4-month treatment and 3-month follow-up. In this study, the investigators aim to define a quantitative relationship between intra-testicular testosterone (IT-T) and spermatogenesis in man. Hormone levels will be measured in a small amount of testicular fluid at the beginning and end of treatment and sperm concentration will be measured.

Official Title
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Mechanisms of Hormonal Control of Spermatogenesis in Man

Conditions
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Gonadotropin Deficiency

Intervention / Treatment
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* Drug: Testosterone 1% Gel
* Drug: Acyline
* Drug: Dutasteride
* Drug: Ketoconazole
* Drug: HCG
* Drug: placebo dutasteride
* Drug: placebo ketoconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males age 18-55 In general good health based on normal screening evaluation Normal serum testosterone, lutenizing hormone (LH) and follicle stimulating hormone (FSH) Prostate Specific Antigen (PSA) < 3.0 Agrees not to donate blood or participate in another research study during the study Informed consent Must be willing to use a reliable form of contraception during the study Exclusion Criteria: Participation in a long-term male contraceptive study within the past three months History of testosterone or anabolic steroid abuse in the past History of or current skin disorder that will interfere with testosterone gel Poor general health or significantly abnormal screening blood results History of or current testicular or prostate disease History of a bleeding disorder or need for anticoagulation History of untreated sleep apnea and/or major psychiatric problems BMI > 32 History of or current liver disease Chronic pain syndrome Current use of terfenidine, astemizole, cisapride, budesonide, felodipine, fluticasone, lovastatin, midazolam, sildenafil, or vardenafil Use of glucocorticoids or underlying adrenal insufficiency Active drug or alcohol abuse within the past year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acyline; T Gel; placebo dutasteride, placebo ketoconazole<br>All men will receive Acyline 300 ug/kg subcutaneous (SQ) injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 1: placebo oral ketoconazole + placebo oral dutasteride for 4 months | Drug: Testosterone 1% Gel<br>* Testosterone 1% gel 5g daily for 4 months [all subjects]<br>* Other names: AndroGel;Drug: Acyline<br>* Acyline 300 ug/kg SQ injections every 2-weeks for 4 months [all subjects]<br>Drug: placebo dutasteride<br>* placebo oral dutasteride PO daily for 4 months<br>Drug: placebo ketoconazole<br>* placebo ketoconazole daily for 4 months<br>|
| Experimental: Acyline; T gel; Ketoconazole; placebo<br>All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 2: oral ketoconazole 400 mg + placebo oral dutasteride for 4 months | Drug: Testosterone 1% Gel<br>* Testosterone 1% gel 5g daily for 4 months [all subjects]<br>* Other names: AndroGel;Drug: Acyline<br>* Acyline 300 ug/kg SQ injections every 2-weeks for 4 months [all subjects]<br>Drug: Ketoconazole<br>* ketoconazole 400 mg PO daily for 4 months<br>Drug: placebo dutasteride<br>* placebo oral dutasteride PO daily for 4 months<br>|
| Experimental: Acyline; Tgel; Ketoconazole; Dutasteride<br>All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 3: Ketoconazole 400mg orally daily + Dutasteride 2.5 mg orally on day 1, followed by 0.5mg daily for 4 months | Drug: Testosterone 1% Gel<br>* Testosterone 1% gel 5g daily for 4 months [all subjects]<br>* Other names: AndroGel;Drug: Acyline<br>* Acyline 300 ug/kg SQ injections every 2-weeks for 4 months [all subjects]<br>Drug: Dutasteride<br>* Dutasteride 2.5 mg (day 1) followed by 0.5 mg daily for 4 months<br>* Other names: Avodart;Drug: Ketoconazole<br>* ketoconazole 400 mg PO daily for 4 months<br>|
| Experimental: Acyline; Tgel; HCG<br>All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned. Group 4: Human Chorionic gonadotropin (HCG) 60 IU injection every other day for 4 months. | Drug: Testosterone 1% Gel<br>* Testosterone 1% gel 5g daily for 4 months [all subjects]<br>* Other names: AndroGel;Drug: Acyline<br>* Acyline 300 ug/kg SQ injections every 2-weeks for 4 months [all subjects]<br>Drug: HCG<br>* HCG 60 IU injection Subcutaneously, every other day for 4 months<br>* Other names: Human chorionic gonadotropin (HCG);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sperm concentration | Difference in sperm concentration at week 16 between 4 treatment groups | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IT steroid concentration | It steroid concentration at week 16 between the 4 treatment groups | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intratesticular androgens, testosterone, dutasteride, gonadotropin suppression, male contraception, spermatogenesis