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

University of Washington

Status and phase: Completed; Phase 2; Phase 1

Conditions: Type 2 Diabetes Mellitus; Androgen Deficiency; Insulin Resistance; Obesity; Metabolic Disease

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01686828

STUDY00002641

Details and patient eligibility

About

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

Full 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.

Enrollment: 53 patients

Sex: Male

Ages: 25 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

53 participants in 4 patient groups

Acyline & placebo gel & placebo pill

Experimental group

Description:

Acyline (300mcg/kg) + placebo transdermal gel + placebo pill daily

Treatment:

Drug: Placebo pill (for Letrozole)

Drug: Placebo gel (for Testosterone 1.62% gel)

Drug: Acyline

Acyline & Testosterone 1.25g & placebo pill

Experimental group

Description:

Acyline (300mcg/kg) + Testosterone gel (1.25g) daily + placebo pill daily

Treatment:

Drug: Testosterone 1.62% gel

Drug: Placebo pill (for Letrozole)

Drug: Acyline

Acyline & Testosterone 5g & placebo pill

Experimental group

Description:

Acyline (300mcg/kg) + Testosterone gel (5g) daily + placebo pill daily

Treatment:

Drug: Testosterone 1.62% gel

Drug: Placebo pill (for Letrozole)

Drug: Acyline

Acyline & Testosterone & Letrozole

Experimental group

Description:

Acyline (300mcg/kg) + Testosterone gel (5g) daily + letrozole (5mg) daily

Treatment:

Drug: Letrozole

Drug: Testosterone 1.62% gel

Drug: Acyline