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

Obesity Clinical Trial

— T-IR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01686828
• Other study ID #: STUDY00002641
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2013
• Est. completion date: December 2017

Study information

• Verified date: April 2018
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 2017
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 25 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Androgen Deficiency
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Metabolic Disease
• Metabolic Diseases
• Obesity
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Acyline
300 mcg/mL administered subcutaneously (at Day 0, Week 2)
• Testosterone 1.62% gel
Transdermal Testosterone Gel (either 1.25g or 5g/d) for 4 weeks
• Letrozole
Letrozole oral aromatase inhibitor 5mg daily for 4 weeks
• 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

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (40)

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Herbst KL, Anawalt BD, Amory JK, Bremner WJ. Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab. 2002 Jul;87(7):3215-20. — View Citation

Herbst KL, Coviello AD, Page S, Amory JK, Anawalt BD, Bremner WJ. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men. J Clin Endocrinol Metab. 2004 Dec;89(12):5959-65. — View Citation

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Sensitivity Quantified by Matsuda Index	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	Changes in Body Composition	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
Secondary	Changes in Adipose Tissue Gene Expression	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

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