T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin, Which Regulates Blood Sugar Levels

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Washington
Sponsor:
Information provided by (Responsible Party):
Katya Rubinow, University of Washington
ClinicalTrials.gov Identifier:
NCT01686828
First received: September 12, 2012
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Insulin Resistance
Type 2 Diabetes Mellitus
Obesity
Androgen Deficiency
Metabolic Disease
Drug: Acyline
Drug: Testosterone 1.62% gel
Drug: Letrozole
Drug: Placebo gel (for Testosterone 1.62% gel)
Drug: Placebo pill (for Letrozole)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Glucose disposal assessed by frequently sampled oral glucose tolerance test (OGTT)


Secondary Outcome Measures:
  • Changes in body composition [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Changes in adipose tissue gene expression [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: June 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acyline & placebo gel & placebo pill
Acyline (300mcg/kg at Day 0 & week 2, by injections) + placebo transdermal gel + placebo aromatase inhibitor daily for 4 weeks
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 Gel 1.25g/d & placebo pill
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
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
Other Name: Androgel
Drug: Placebo pill (for Letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Experimental: Acyline & Testosterone Gel 5g/d & placebo pill
Acyline (300mcg/kg every 2 weeks, by injections) + Testosterone 1.62% gel (5g) daily + placebo aromatase inhibitor pill daily for 4 weeks
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
Other Name: Androgel
Drug: Placebo pill (for Letrozole)
Oral placebo aromatase inhibitor to mimic Letrozole 5mg/d
Experimental: Acyline & Testosterone gel & Letrozole
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
Drug: Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
Drug: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks
Other Name: Androgel
Drug: Letrozole
Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Other Name: Femara

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.

  Eligibility

Ages Eligible for Study:   25 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686828

Contacts
Contact: Katya Rubinow, MD 206-616-1818 rubinow@uw.edu
Contact: Genecelle Delossantos 206 779-9496 gen7@uw.edu

Locations
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Genecelle Delossantos    206-221-3490    gen7@uw.edu   
Contact: Kathy Winter    206-616-0484    klwinter@uw.edu   
Principal Investigator: Katya Rubinow, MD         
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications:

Responsible Party: Katya Rubinow, Assistant Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01686828     History of Changes
Other Study ID Numbers: 43007-B
Study First Received: September 12, 2012
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
insulin
androgens
insulin resistance
testosterone
estradiol
obesity

Additional relevant MeSH terms:
Insulin Resistance
Diabetes Mellitus
Diabetes Mellitus, Type 2
Metabolic Diseases
Obesity
Glucose Metabolism Disorders
Endocrine System Diseases
Hyperinsulinism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Androgens
Methyltestosterone
Letrozole
Insulin
Aromatase Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on July 20, 2014