Hypogonadism in Young Men With Type 2 Diabetes

Study Overview
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Brief Summary
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Low testosterone production, known clinically as hypogonadism, appears to be common complication of type 2 diabetes, affecting one in three diabetic men. Hypogonadism is known to be associated with decreased muscle mass, increased fat mass, increased inflammation and decreased fertility. In this grant, the investigators propose to study the effects of having low testosterone on 1) insulin sensitivity, the ability of the body to handle glucose 2) fat and muscle mass at specific areas of the body 3) expression of mediators of inflammation in the blood 4) semen quality. This study will compare diabetic men (with or without hypogonadism). This study will also evaluate the effect of treatment with clomiphene (a drug that increases testosterone and sperm production) or testosterone in men with diabetes and hypogonadism. The investigators hope that this project will help us understand the state of hypogonadism in young type 2 diabetic men who are in their peak fertility years and give us insights into treatment of this condition. With the rising prevalence of type 2 diabetes in the young, this project may have implications for public health.

Detailed Description
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This project will study young men with type 2 diabetes. We have shown that half of these men have low testosterone levels. This can lead to 1) Low muscle mass; 2) more fat mass; 3) insulin resistance; 4) low sperm count and 5) increased inflammation (that increases the risk of heart disease). This project will study these consequences in detail and also the possibility of reversing them with treatment. Information from this project will be useful in planning of future studies that will evaluate the effect of treatment of low testosterone on mortality, heart disease and stroke.

Official Title
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Effect of Hypogonadotropic Hypogonadism and Replacement With Clomiphene Citrate and Testosterone on Insulin Sensitivity, Body Composition, Inflammation, Sexual Function and Spermatogenesis in Young Type 2 Diabetic Men

Conditions
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Hypogonadotropic Hypogonadism, Type 2 Diabetes

Intervention / Treatment
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* Drug: testosterone
* Drug: clomiphene
* Drug: placebo
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2D Males with age 18-40 years Exclusion Criteria: planning to have children in the next one year Use of androgens, CC, hCG, aromatase inhibitors or over the counter health supplements which contain androgens currently or in the past 6 months; PSA > 4ng/ml, symptoms of severe BPH, prostate nodule or severe enlargement on digital rectal examination or h/o prostatic carcinoma Hemoglobin A1c > 8% Hematocrit > 50% History of obstructive sleep apnea Congestive heart failure Use of thiazolidinediones or exenatide currently suffering from depression, with or without treatment history of severe depression in the past which needed hospitalization currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition Coronary event or procedure in the previous 6 months Hepatic disease (transaminase > 3 times normal) or cirrhosis Renal impairment (serum creatinine > 1.5) HIV or Hepatitis C positive status Participation in any other concurrent clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: testosterone<br>intramuscular injections every 2 weeks | Drug: testosterone<br>* intramuscular every 2 weeks<br>|
| Experimental: clomiphene<br>oral drug thrice a week | Drug: clomiphene<br>* thrice a week<br>|
| Placebo Comparator: placebo for testosterone<br>placebo for testosterone arm | Drug: placebo<br>* intramuscular saline injections every 2 weeks<br>|
| Placebo Comparator: placebo for clomiphene<br>oral placebo for clomiphene arm | Drug: placebo<br>* oral<br>|
| No Intervention: eugonadal obese<br>obese men with normal testosterone level | |
| No Intervention: lean<br>healthy lean men (control) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Resistance | To compare the insulin sensitivity as measured by whole body glucose uptake during hyperinsulinemic euglycemic (HE) clamp in young T2D men with and without HH. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypogonadism, diabetes, spermatogenesis, insulin resistance