Clinical trial NCT01686828: T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin
Official title: Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Insulin Resistance
Type 2 Diabetes Mellitus
Obesity
Androgen Deficiency
Metabolic Disease
Keywords: insulin
androgens
insulin resistance
testosterone
estradiol
obesity
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2012-09-18
Enrollment: 53
Sex: MALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to understand the effects of testosterone and estrogen on the body's response to the hormone insulin.

Detailed description: The investigators will examine the effects of testosterone on insulin sensitivity and body composition in men. This study may lend greater insight into the increased risk of diabetes evident in men with low circulating levels of testosterone. Three drugs will be used in this study: acyline, given by injection; testosterone (T) gel that is applied to the skin; and letrozole, which is an oral drug that blocks the conversion of androgens (male hormones) to estrogens (female hormones). Acyline inhibits the production of luteinizing hormone (LH) and follicle stimulating hormone (FSH). When acyline stops the production of these hormones, it blocks the signal from the brain that stimulates the testicles to make testosterone. Adding testosterone to acyline will restore physiologic levels of testosterone in some study participants. One group of men will receive T gel with letrozole, an aromatase inhibitor; these men will have normal levels of testosterone but low levels of estrogen in the blood. This design will enable determination of the respective metabolic effects of testosterone and estrogen.

Eligibility criteria: Inclusion Criteria:

* Prostate-specific antigen (PSA) ≤ 3 ng/mL
* Age 25-55 years
* Ability to understand the study, study procedures and provide informed consent
* Serum total T \> 300 ng/dL
* Normal reproductive history and exam
* International Prostate Symptom Score (IPSS) \< 11

Exclusion Criteria:

* A history of prostate cancer including suspicious digital rectal exam (DRE) or history of highgrade prostatic intraepithelial neoplasia (PIN) on prostate biopsy
* Invasive therapy for benign prostatic hyperplasia (BPH) in the past
* History of acute urinary retention in the previous 3 months
* Current or recent past use of androgenic or anti-androgenic drugs, steroids or drugs which interfere with steroid metabolism (within the last 3 months)
* Current use of statins or glucocorticoids
* Severe systemic illness (renal, liver, cardiac, lung disease, cancer, diabetes mellitus) or skin disease
* A history of or current breast cancer
* Known, untreated obstructive sleep apnea
* Hematocrit \> 50 or \< 34
* Hypersensitivity to any of the drugs used in the study
* History of a bleeding disorder or anticoagulation
* Participation in any other drug study within past 90 days
* History of drug or alcohol abuse within the last 12 months
* Weight \> 280 lbs. or BMI ≥ 33
* Desire for fertility in the next 6 months or current pregnant partner
* Sperm concentration \<14 million/ml
* Significant, uncontrolled hypertension (BP \>160/100 mmHg); subjects with well-controlled BP on medical therapy will be eligible to participate

Primary outcomes:
measure: Insulin Sensitivity Quantified by Matsuda Index
timeFrame: 4 weeks
Secondary outcomes:
measure: Changes in Body Composition
timeFrame: 4 weeks
measure: Changes in Adipose Tissue Gene Expression
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: William J Bremner, MD, PhD
role: STUDY_CHAIR
affiliation: University of Washington
name: Stephanie T Page, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Washington
name: Katya Rubinow, MD
role: PRINCIPAL_INVESTIGATOR
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