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

April 5, 2018 updated by: Katya Rubinow, University of Washington

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

53

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acyline & placebo gel & placebo pill
Acyline (300mcg/kg) + placebo transdermal gel + placebo pill daily
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Placebo gel (for Testosterone 1.62% gel)
placebo gel manufactured to mimic Testosterone 1.62% gel
Drug: Placebo pill (for Letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Experimental: Acyline & Testosterone 1.25g & placebo pill
Acyline (300mcg/kg) + Testosterone gel (1.25g) daily + placebo pill daily
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Placebo pill (for Letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks
Other Names:
  • Androgel
Experimental: Acyline & Testosterone 5g & placebo pill
Acyline (300mcg/kg) + Testosterone gel (5g) daily + placebo pill daily
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Placebo pill (for Letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks
Other Names:
  • Androgel
Experimental: Acyline & Testosterone & Letrozole
Acyline (300mcg/kg) + Testosterone gel (5g) daily + letrozole (5mg) daily
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks
Other Names:
  • Androgel
Drug: Letrozole
Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin Sensitivity Quantified by Matsuda Index
Time Frame: 4 weeks
Whole body insulin sensitivity as quantified by Matsuda Index at the end of the treatment period, calculated by the following equation: 10,000/square root of(FPG*FI)*(FPG+PG30*2+PG60*2+PG90*2+PG120)/8*(FPI+PI30*2+PI60*2+PI90*2+PI)/8). FPG=fasting plasma glucose level; FPI=fasting plasma insulin level; PG30,60,90, and 120=plasma glucose levels sampled at 30,60,90, and 120 minutes after oral glucose load; PI30,60,90, and 120=plasma insulin levels sampled at 30,60,90, and 120 minutes after the oral glucose load
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Body Composition
Time Frame: 4 weeks
Fat mass and lean mass were measured by dual energy X-ray absorptiometry (DEXA) at baseline and at the end of the 4 week treatment period
4 weeks
Changes in Adipose Tissue Gene Expression
Time Frame: 4 weeks
We examined whether differences in lipoprotein lipase expression would be evident across study treatment groups. RNA was isolated from whole adipose tissue gene expression, and complementary DNA (cDNA) was synthesized from 1.5 ug of RNA per sample. Gene expression was measured by polymerase chain reaction (PCR) using predesigned TaqMan® Gene Expression Assays. Standard curves were included on each plate, so Ct values were converted to copy numbers of the target gene. Expression values were normalized to the geometric mean of the housekeeping genes phosphoglycerate kinase and 18s.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Investigators

  • Study Chair: William J Bremner, MD, PhD, University of Washington
  • Study Director: Stephanie T Page, MD, PhD, University of Washington
  • Principal Investigator: Katya Rubinow, MD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2013

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

September 17, 2012

First Posted (Estimate)

September 18, 2012

Study Record Updates

Last Update Posted (Actual)

May 8, 2018

Last Update Submitted That Met QC Criteria

April 5, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00002641

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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