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Trial record 1 of 1 for:    NCT01686828
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T-IR- Study to Understand the Effects of Testosterone and Estrogen on the Body's Response to the Hormone Insulin (T-IR)

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ClinicalTrials.gov Identifier: NCT01686828
Recruitment Status : Completed
First Posted : September 18, 2012
Results First Posted : June 14, 2017
Last Update Posted : May 8, 2018
Sponsor:
Information provided by (Responsible Party):
Katya Rubinow, University of Washington

Study Description
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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.

Condition or disease Intervention/treatment 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

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 53 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Androgen-mediated Pathways in the Regulation of Insulin Sensitivity in Men
Actual Study Start Date : June 2013
Actual Primary Completion Date : May 2015
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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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: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g 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 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: Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g 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 & 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 Name: Androgel

Drug: Letrozole
Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
Other Name: Femara


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01686828


Locations
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United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Investigators
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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
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Additional Information:

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Katya Rubinow, Assistant Professor, Division of Metabolism, Endocrinology and Nutrition, University of Washington
ClinicalTrials.gov Identifier: NCT01686828    
Other Study ID Numbers: STUDY00002641
First Posted: September 18, 2012    Key Record Dates
Results First Posted: June 14, 2017
Last Update Posted: May 8, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Katya Rubinow, University of Washington:
insulin
androgens
insulin resistance
 testosterone
estradiol
obesity
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Insulin Resistance
Metabolic Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Endocrine System Diseases
Hyperinsulinism
Letrozole
Methyltestosterone
Acyline
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
 Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgens
Hormones
Antineoplastic Agents, Hormonal
Anabolic Agents