Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men
A. HYPOTHESES: In older men low testosterone levels, abdominal obesity and elevated fasting insulin who are at risk for the cardiovascular complications such as heart attack and stroke.
- Supplemental testosterone will decrease abdominal fat (visceral adominal adipose tissues (VAT), subcutaneous abdominal adipose tissue (SAT), and hepatic fat) and intramyocellular lipid in peripheral muscles(IMCL).
Supplemental testosterone will improve insulin sensitivity by:
- Decreasing hepatic glucose output (HGO), a measure of central insulin resistance
- Decreasing VAT
- Decreasing SAT
- Increasing adiponectin production
- Improving peripheral glucose disposal (Rd) by reducing IMCL
- Increasing appendicular skeletal muscle mass and basal metabolic rate
- Primary Objective: To determine the effects of supplemental testosterone to achieve testosterone levels in the upper normal physiologic range on central adipose tissue (abdominal VAT, SAT, and hepatic fat) and peripheral skeletal muscle fat (IMCL and intermyocellular fat).
Secondary Objectives: To determine the effects of supplemental testosterone to achieve testosterone levels in the upper normal physiologic range:
- on hepatic glucose output (HGO) and peripheral glucose disposal (Rd)
- on hepatic glucose synthesis from glycogen, glycerol and the Krebs cycle using [1,6-13C2C] glucose, D2O, and [U-13C3] palmitate isotope dilution studies
- on adiponectin and apoprotein B levels
- on basal metabolic rate (REE, R/Q) as related to changes in skeletal muscle mass
Results of this study will provide greater understanding whether androgen therapy enhances insulin sensitivity by decreasing HGO, decreasing adiponectin production, improving peripheral Rd and if these desired effects are achieved, whether they are due to reductions in VAT, SAT, liver fat, IMCL or effects of augmenting muscle mass per se. Results will generate hypotheses to investigate cellular and molecular mechanisms of androgen effects in persons at risk for the Metabolic Syndrome.
Drug: Topical testosterone (Androgel) 10 g/day
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- Regional adipose tissue (visceral and subcutaneous abdominal [VAT, SAT] by MRI, Hepatic fat mass by 1H-MRI spectroscopy [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- IMCL [intramyocellular lipid] by 1H-MRI spectroscopy) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Total appendicular and intermuscular fat by Tomovision analysis of MRI images [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Total and regional carbohydrate metabolism during a 2-hr hyperinsulinemic euglycemic clamp and [6,6-2H2] glucose studies (peripheral glucose disposal [Rd],hepatic glucose output [HGO]) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Skeletal muscle mass by DEXA and MRI [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
- Exploratory measures (adiponectin and Apolipoprotein B levels) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||December 2014|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Single arm
Open label treatment with each participant serving as his own control. Data is compared before and after treatment.
Drug: Topical testosterone (Androgel) 10 g/day
Testosterone therapy for 20 weeks
Study Design: This is an investigator-initiated open label, study to investigate the effects of supplemental testosterone to increase testosterone levels to the upper normal range in 12 older hypogonadal (testosterone levels less than 300 ng/dL) men with abdominal obesity and elevated fasting insulin levels. Subjects will be assigned to receive 10 g of transdermal testosterone (Androgel) every morning to achieve levels in the upper normal physiologic range (similar to men in the 3rd and 4th decades) for 20 weeks.
- For the primary objective, regional adipose tissue, namely abdominal VAT, abdominal SAT, hepatic fat, and IMCL will be imaged by MRI and 1H-spectroscopy at baseline (study week 0) and at study week 20 (completion of study therapy).
- For the secondary objective, insulin sensitivity (peripheral Rd, hepatic glucose output [HGO]) and hepatic gluconeogenesis will be measured directly during a two stage hyperinsulinemic euglycemic clamp at baseline and study week 20.
- Indirect markers of lipid (adiponectin, ApoB 100) and carbohydrate metabolism (Fasting blood sugar, HOMA-IR, QUICKI) along with DEXA analysis of regional adipose and appendicular lean tissue (mainly skeletal muscle) will be measured at baseline, study week 10, and study week 20.
All components of the study will be conducted in the USC NIH-funded (NCRR), General Clinical Research Center.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00365794
|United States, California|
|LAC-USC Medical Center GCRC|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Fred R Sattler, MD||University of Southern California|