View Clinical Trial (Medical Research Study)
Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men
| City: |
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Los Angeles |
| State: |
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California |
| Zip Code: |
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90033 |
| Conditions: |
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Aging - Obesity - Insulin Resistance - Hypogonadism |
| Purpose: |
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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.
1. 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).
2. Supplemental testosterone will improve insulin sensitivity by:
1. Decreasing hepatic glucose output (HGO), a measure of central insulin resistance
2. Decreasing VAT
3. Decreasing SAT
4. Increasing adiponectin production
5. Improving peripheral glucose disposal (Rd) by reducing IMCL
6. Increasing appendicular skeletal muscle mass and basal metabolic rate
B. OBJECTIVES:
1. 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).
2. Secondary Objectives: To determine the effects of supplemental testosterone to achieve
testosterone levels in the upper normal physiologic range:
1. on hepatic glucose output (HGO) and peripheral glucose disposal (Rd)
2. on hepatic glucose synthesis from glycogen, glycerol and the Krebs cycle using
[1,6-13C2C] glucose, D2O, and [U-13C3] palmitate isotope dilution studies
3. on adiponectin and apoprotein B levels
4. 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.
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| Study Summary: |
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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.
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| Criteria: |
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Inclusion Criteria:
- Entry Criteria:
- Men > 60 years of age
- Total testosterone < 300 ng/dL
- Waist circumference >102 cm
- Fasting insulin level > 18 U/L
Exclusion Criteria:
- PSA > 4.1, symptoms of obstructive uropathy (AUA score > 14), unexplained prostate
nodule or gland firmness
- Hematocrit > 50%
- Malignancy other than cutaneous cancers
- Sleep apnea requiring CPAP
- History of myocardial infarction, angina or stroke within the previous 6 months
- Clinical diagnosis of diabetes or FPG > 126 mg/dL
- Hypothyroidism not controlled to euthyroid levels with medication for at least 3
months
- LDL-C >160 mg/dL
- Transaminases > 1.5X ULN
- Systemic anticoagulation with warfarin
- Active progressive resistance training
- Dieting for weight loss
- Active inflammatory condition (e.g. rheumatoid arthritis)
- Use of any anabolic agent (e.g. growth hormone, testosterone precursor, anabolic
steroid)or cytokine therapy in the proceeding 12 months
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| NCT ID: |
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NCT00365794 |
| Primary Contact: |
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Principal Investigator
Fred R Sattler, MD
University of Southern California
Yolanda Stewart
Phone: 323-226-7571 ext. 7571
Email: cerda@usc.edu
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| Backup Contact: |
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N/A |
| Location Contact: |
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Los Angeles, California 90033
United States
There is no listed contact information for this specific location.
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 18, 2013 |
| Modifications to this listing: |
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