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

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT01686828
Collaborator
(none)
53
Enrollment
1
Location
4
Arms
54
Actual Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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
  • 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

Study Type:
Interventional
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 :
Jun 1, 2013
Actual Primary Completion Date :
May 1, 2015
Actual Study Completion Date :
Dec 1, 2017

Arms and Interventions

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 Names:
  • 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 Names:
  • 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 Names:
  • Androgel

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Insulin Sensitivity Quantified by Matsuda Index [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 [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 [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

    Criteria

    Ages Eligible for Study:
    25 Years to 55 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    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

    Locations

    Site City State Country Postal Code
    1 University of Washington Seattle Washington United States 98195

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    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:
    Sep 18, 2012
    Last Update Posted:
    May 8, 2018
    Last Verified:
    Apr 1, 2018
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Katya Rubinow, Assistant Professor, Division of Metabolism, Endocrinology and Nutrition, University of Washington
    insulin
    androgens
    insulin resistance
    testosterone
    estradiol
    obesity
    Additional relevant MeSH terms:
    Diabetes Mellitus, Type 2
    Insulin Resistance
    Metabolic Diseases
    Letrozole
    Methyltestosterone
    Acyline
    Testosterone
    Testosterone undecanoate
    Testosterone enanthate
    Testosterone 17 beta-cypionate

    Study Results

    Participant Flow

    Recruitment Details Recruitment period: 06/01/13-11/30/2014 Location: University/Medical Center Flyers, newspaper ads, online postings
    Pre-assignment Detail 116 subjects were screened, 63 subjects didn't meet study inclusion/exclusion criteria or they withdrew consent prior to group assignment, and 3 subjects withdrew prior to the baseline visit.
    Arm/Group Title Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Arm/Group Description 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 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: 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 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: 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 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: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
    Period Title: Overall Study
    STARTED 13 14 13 13
    COMPLETED 12 13 12 13
    NOT COMPLETED 1 1 1 0

    Baseline Characteristics

    Arm/Group Title Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole Total
    Arm/Group Description 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 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: 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 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: 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 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: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks Total of all reporting groups
    Overall Participants 13 14 13 13 53
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    37
    35
    42
    34
    36
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    13
    100%
    14
    100%
    13
    100%
    13
    100%
    53
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    1
    1.9%
    Not Hispanic or Latino
    9
    69.2%
    11
    78.6%
    11
    84.6%
    13
    100%
    44
    83%
    Unknown or Not Reported
    3
    23.1%
    3
    21.4%
    2
    15.4%
    0
    0%
    8
    15.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    2
    15.4%
    0
    0%
    0
    0%
    0
    0%
    2
    3.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    7.7%
    2
    14.3%
    0
    0%
    2
    15.4%
    5
    9.4%
    White
    7
    53.8%
    8
    57.1%
    11
    84.6%
    11
    84.6%
    37
    69.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    3
    23.1%
    4
    28.6%
    2
    15.4%
    0
    0%
    9
    17%
    Region of Enrollment (participants) [Number]
    United States
    13
    100%
    14
    100%
    13
    100%
    13
    100%
    53
    100%
    Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m2]
    26
    (4)
    26
    (4)
    25
    (2)
    25
    (4)
    25
    (3)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    82
    (14)
    81
    (15)
    78
    (8)
    82
    (11)
    81
    (12)
    Fasting Glucose (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    97
    (6)
    97
    (13)
    101
    (7)
    98
    (9)
    98
    (9)
    Percentage Body Fat (%total body mass) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [%total body mass]
    28
    (7)
    23
    (6)
    24
    (4)
    23
    (7)
    24
    (6)
    Percentage Lean Mass (%total body mass) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [%total body mass]
    68
    (7)
    73
    (5)
    72
    (4)
    73
    (7)
    72
    (6)

    Outcome Measures

    1. Primary Outcome
    Title Insulin Sensitivity Quantified by Matsuda Index
    Description 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
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Of the 53 subjects who attended the baseline study visit, 2 withdrew from the study and 1 was discontinued due to a protocol violation. 50 subjects completed the week 10 study visit. Of these, 5 subjects were excluded from the final analyses; 1 was found to have undiagnosed diabetes, and 4 subjects were excluded due to study drug non-adherence.
    Arm/Group Title Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Arm/Group Description 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 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: 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 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: 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 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: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
    Measure Participants 10 11 11 13
    Median (Inter-Quartile Range) [units on a scale]
    5.0
    9.4
    7.2
    7.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Acyline & Placebo Gel & Placebo Pill, Acyline & Testosterone Gel 1.25g/d & Placebo Pill, Acyline & Testosterone Gel 5g/d & Placebo Pill, Acyline & Testosterone Gel & Letrozole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.164
    Comments The a prior threshold for statistical significance was p<0.05.
    Method RM-ANOVA
    Comments
    2. Secondary Outcome
    Title Changes in Body Composition
    Description 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
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Arm/Group Description 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 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: 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 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: 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 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: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
    Measure Participants 10 11 11 13
    Change in fat mass
    1.1
    (0.8)
    0.7
    (0.5)
    -0.4
    (1.0)
    0.5
    (0.8)
    Change in lean mass
    -1.2
    (1.0)
    -1.4
    (1.5)
    0.0
    (1.0)
    -0.3
    (1.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Acyline & Placebo Gel & Placebo Pill, Acyline & Testosterone Gel 1.25g/d & Placebo Pill, Acyline & Testosterone Gel 5g/d & Placebo Pill, Acyline & Testosterone Gel & Letrozole
    Comments Time-by-group interaction for fat mass
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments
    Method RM-ANOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Acyline & Placebo Gel & Placebo Pill, Acyline & Testosterone Gel 1.25g/d & Placebo Pill, Acyline & Testosterone Gel 5g/d & Placebo Pill, Acyline & Testosterone Gel & Letrozole
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.03
    Comments Time-by-group interaction for lean mass
    Method RM-ANOVA
    Comments
    3. Secondary Outcome
    Title Changes in Adipose Tissue Gene Expression
    Description 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.
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Subjects were included who had adipose tissue samples available from both baseline and week 4 (end-of-treatment) visits.
    Arm/Group Title Acyline + Placebo Gel + Placebo Pills Acyline + Testosterone Gel (1.25g/d) + Placebo Pills Acyline + Testosterone Gel (5g/d) + Placebo Pills Acyline + Testosterone Gel (5g/d) + Letrozole
    Arm/Group Description Acyline (300 mg/kg, subcutaneous injection at weeks 0, 2) + placebo gel + oral placebo pills daily. This treatment regimen resulted in medical castration. Acyline (300 mcg/kg, subcutaneous injection at weeks 0, 2) + testosterone gel administered daily + daily placebo pills. This group was intended to have low-normal levels of serum testosterone and estradiol. Acyline (300 mcg/kg, subcutaneous injection at weeks 0, 2) + testosterone gel administered daily + daily placebo pills. This group was intended to have normal, physiologic levels of serum testosterone and estradiol. Acyline (300 mcg/kg, subcutaneous injection at weeks 0, 2) + testosterone gel administered daily + daily letrozole (pills). This group was intended to have normal levels of serum testosterone with selective estrogen deficiency.
    Measure Participants 10 11 11 13
    Mean (Standard Deviation) [gene copy number per ng RNA]
    7493
    (1293)
    8224
    (3485)
    7885
    (2736)
    8320
    (3133)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Acyline & Placebo Gel & Placebo Pill
    Comments The null hypothesis was that short-term testosterone deprivation would not affect lipoprotein lipase expression in adipose tissue. Repeated measures ANOVA was used to determine if a time-by-group effect was apparent for lipoprotein lipase expression.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value >0.1
    Comments
    Method ANOVA
    Comments

    Adverse Events

    Time Frame Adverse events were recorded through study completion, and subjects who experienced adverse events during the study were followed for up to 6 months after study participation ended.
    Adverse Event Reporting Description There were numerous, mild complications reported for the fat biopsy procedure such as bleeding, bruising, hematomas, tenderness, redness etc which are not listed. A frequency threshold of >15% was used for reported events.
    Arm/Group Title Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Arm/Group Description 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 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: 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 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: 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 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: Transdermal Testosterone Gel (either 3.75g or 5g/d) for 4 weeks Letrozole: Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
    All Cause Mortality
    Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/13 (15.4%) 1/14 (7.1%) 0/13 (0%) 0/13 (0%)
    Cardiac disorders
    Cardiac Arrthymia 1/13 (7.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0
    Endocrine disorders
    Elevated PSA level 0/13 (0%) 0 1/14 (7.1%) 1 0/13 (0%) 0 0/13 (0%) 0
    Hepatobiliary disorders
    Abnormal Liver enzyme (AST & ALT) levels 1/13 (7.7%) 1 0/14 (0%) 0 0/13 (0%) 0 0/13 (0%) 0
    Other (Not Including Serious) Adverse Events
    Acyline & Placebo Gel & Placebo Pill Acyline & Testosterone Gel 1.25g/d & Placebo Pill Acyline & Testosterone Gel 5g/d & Placebo Pill Acyline & Testosterone Gel & Letrozole
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/13 (69.2%) 9/14 (64.3%) 7/13 (53.8%) 10/13 (76.9%)
    Endocrine disorders
    Hot Flashes 3/13 (23.1%) 3 1/14 (7.1%) 1 1/13 (7.7%) 1 0/13 (0%) 0
    Low libido 4/13 (30.8%) 4 4/14 (28.6%) 4 0/13 (0%) 0 5/13 (38.5%) 5
    Decreased testes size 4/13 (30.8%) 4 2/14 (14.3%) 2 2/13 (15.4%) 2 0/13 (0%) 0
    General disorders
    Low Energy 0/13 (0%) 0 3/14 (21.4%) 3 1/13 (7.7%) 1 1/13 (7.7%) 1
    Irritability 2/13 (15.4%) 2 0/14 (0%) 0 0/13 (0%) 0 1/13 (7.7%) 1
    Fatigue 0/13 (0%) 0 0/14 (0%) 0 3/13 (23.1%) 3 2/13 (15.4%) 2
    Nervous system disorders
    Erectile Dysfunction 2/13 (15.4%) 2 0/14 (0%) 0 0/13 (0%) 0 2/13 (15.4%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Katya Rubinow
    Organization University of Washington
    Phone 206-7543-3470
    Email rubinow@uw.edu
    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:
    Sep 18, 2012
    Last Update Posted:
    May 8, 2018
    Last Verified:
    Apr 1, 2018