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

Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men

Sponsors

Lead Sponsor: University of Washington

Source University of Washington
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.

Overall Status Completed
Start Date June 2013
Completion Date December 2017
Primary Completion Date May 2015
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Insulin Sensitivity Quantified by Matsuda Index 4 weeks
Secondary Outcome
Measure Time Frame
Changes in Body Composition 4 weeks
Changes in Adipose Tissue Gene Expression 4 weeks
Enrollment 53
Condition
Intervention

Intervention Type: Drug

Intervention Name: Acyline

Description: 300 mcg/mL administered subcutaneously (at Day 0, Week 2)

Intervention Type: Drug

Intervention Name: Testosterone 1.62% gel

Description: Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks

Other Name: Androgel

Intervention Type: Drug

Intervention Name: Letrozole

Description: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks

Arm Group Label: Acyline & Testosterone & Letrozole

Other Name: Femara

Intervention Type: Drug

Intervention Name: Placebo gel (for Testosterone 1.62% gel)

Description: placebo gel manufactured to mimic Testosterone 1.62% gel

Arm Group Label: Acyline & placebo gel & placebo pill

Intervention Type: Drug

Intervention Name: Placebo pill (for Letrozole)

Description: Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d

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

Gender: Male

Minimum Age: 25 Years

Maximum Age: 55 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Location
Facility: University of Washington
Location Countries

United States

Verification Date

April 2018

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Washington

Investigator Full Name: Katya Rubinow

Investigator Title: Assistant Professor, Division of Metabolism, Endocrinology and Nutrition

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Acyline & placebo gel & placebo pill

Type: Experimental

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

Label: Acyline & Testosterone 1.25g & placebo pill

Type: Experimental

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

Label: Acyline & Testosterone 5g & placebo pill

Type: Experimental

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

Label: Acyline & Testosterone & Letrozole

Type: Experimental

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

Acronym T-IR
Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Source: ClinicalTrials.gov