Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome

Study Overview
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Brief Summary
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The purpose of the study is to examine the effect of testosterone treatment on insulin in men with the metabolic syndrome with testosterone levels at or below the lower end of the normal range.

Detailed Description
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The metabolic syndrome is a medical condition defined by high cholesterol levels, high blood pressure, increased abdominal obesity (gain in fat around the region of the stomach), and insulin resistance. Insulin is the hormone that your body produces to decrease the levels of sugar in your blood. A person that is insulin resistant needs more insulin to decrease blood sugar levels than a normal person does. Insulin resistance can lead to type 2 diabetes, which is one of the most common illnesses in the United States. There is evidence pointing to a relationship between insulin and testosterone in men (testosterone is the male sex hormone that is produced in the testes). As men get older their testosterone levels decrease while their weight and insulin resistance tends to increase. The purpose of this research study is to learn more about the details of the relationship between insulin and testosterone. A clearer understanding of this relationship can have an important impact on public health due to the high rate of health problems associated with diabetes, obesity, and heart disease. We are looking for men between the ages of 50-75 with the metabolic syndrome to participate in this research study. Participation in this study involves taking medication and/or placebo (a placebo looks exactly like the study medication but contains no active drug), blood tests, muscle biopsies, and imaging scans. This study involves outpatient visits. Subjects are paid up to $500 for completing the study.

Official Title
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Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Zoladex
* Drug: Testosterone gel
* Drug: Anastrozole Pill
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs) Exclusion Criteria: No new diagnosis of type 2 diabetes or on oral hypoglycemic agents No history of testicular disorders No history of bleeding disorders (i.e. Pulmonary Embolism, Deep Vein Thrombosis, stroke, hypercoagulable syndrome) No history of prostate cancer No previous diagnosis of osteoporosis No history of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence) No symptoms of urinary outflow obstruction or medications for prostate disease No illicit drug use or heavy alcohol use (>4 drinks/day)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo injection, gel and pill | Other: Placebo<br> <br> |
| Active Comparator: Testosterone only<br>Zoladex 3.6 mg IM injection Testosterone 7.5 g gel (AndroGel) transdermally daily Anastrozole 10 mg (Arimidex) orally daily | Drug: Zoladex<br> <br> Drug: Testosterone gel<br> <br> * Other names: AndroGel;Drug: Anastrozole Pill<br> <br> * Other names: Arimidex;|
| Active Comparator: Testosterone and Estrogen<br>Zoladex 3.6 mg IM injection Testosterone 7.5 g gel (AndroGel) transdermally Placebo pill orally daily | Drug: Zoladex<br> <br> Drug: Testosterone gel<br> <br> * Other names: AndroGel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Assessed by euglycemic-hyperinsulinemic clamp | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting energy expenditure | Indirect calorimetry | 3 months | 
| Lipid profile | Fasting lipids | 3 months | 
| Body composition | DXA scan | 3 months | 
| Intramyocellular fat | MR spectroscoopy | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, obesity, testosterone, diabetes, metabolic syndrome, aging