T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin

Condition(s) targeted: Insulin Resistance; Type 2 Diabetes Mellitus; Obesity; Androgen Deficiency; Metabolic Disease

Intervention: Acyline (Drug); Testosterone 1.62% gel (Drug); Letrozole (Drug); Placebo gel (for Testosterone 1.62% gel) (Drug); Placebo pill (for Letrozole) (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
William J Bremner, MD, PhD, Study Chair, Affiliation: University of Washington
Stephanie T Page, MD, PhD, Study Director, Affiliation: University of Washington
Katya Rubinow, MD, Principal Investigator, Affiliation: University of Washington

The purpose of this research study is 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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Insulin sensitivity

Secondary outcome:

Changes in body composition

Changes in adipose tissue gene expression

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.

Minimum age: 25 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- 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 DRE or history of highgrade PIN on

prostate biopsy

- Invasive therapy for 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

University of Washington, Seattle, Washington 98195, United States

Dedicated to basic and clinical research focused primarily on the male reproductive system.

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Starting date: June 2013
Last updated: December 16, 2014