Overview

This trial is active, not recruiting.

Conditions insulin resistance, type 2 diabetes mellitus, obesity, androgen deficiency, metabolic disease
Treatments acyline, testosterone 1.62% gel, letrozole, placebo gel (for testosterone 1.62% gel), placebo pill (for letrozole)
Phase phase 1/phase 2
Sponsor University of Washington
Start date June 2013
End date June 2017
Trial size 60 participants
Trial identifier NCT01686828, 43007-B

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Acyline (300mcg/kg at Day 0 & week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks
acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
placebo gel (for testosterone 1.62% gel)
placebo gel manufactured to mimic Testosterone 1.62% gel
placebo pill (for letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
(Experimental)
Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone 1.62% gel (1.25g) daily + placebo aromatase inhibitor pill daily for 4 weeks
acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
testosterone 1.62% gel Androgel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
placebo pill (for letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
(Experimental)
Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks
acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
testosterone 1.62% gel Androgel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
placebo pill (for letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
(Experimental)
Acyline (300mcg/kg at Day 0 & week 2, by injections) + Testosterone transdermal 1.62% gel (5g) daily + letrozole (5mg) aromatase inhibitor pill daily for 4 weeks
acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
testosterone 1.62% gel Androgel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
letrozole Femara
Letrozole oral aromatase inhibitor 5mg daily for 4 weeks

Primary Outcomes

Measure
Insulin sensitivity
time frame: 4 weeks

Secondary Outcomes

Measure
Changes in body composition
time frame: 4 weeks
Changes in adipose tissue gene expression
time frame: 4 weeks

Eligibility Criteria

Male participants from 25 years up to 55 years old.

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

Additional Information

Official title Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men
Principal investigator Katya Rubinow, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by University of Washington.