Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men - Full Text View

Sponsor:	University of Southern California
Collaborator:	Solvay Pharmaceuticals
Information provided by:	University of Southern California
ClinicalTrials.gov Identifier:	NCT00365794

Purpose

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:
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:

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:
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.

Condition	Intervention	Phase
Aging Obesity Insulin Resistance Hypogonadism	Drug: Topical testosterone (Androgel) 10 g/day	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Prevention

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Obesity

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by University of Southern California:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	12
Study Start Date:	August 2006
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Testosterone therapy for 20 weeks

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	60 Years to 90 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365794

Contacts

Contact: Yolanda Stewart

323-226-7571 ext 7571

cerda@usc.edu

Locations

United States, California
LAC-USC Medical Center GCRC	Recruiting
Los Angeles, California, United States, 90033

Sponsors and Collaborators

University of Southern California

Solvay Pharmaceuticals

Investigators

Principal Investigator:

Fred R Sattler, MD

University of Southern California

More Information

No publications provided

Responsible Party:	Fred R. Sattler, MD, University of Southern California
ClinicalTrials.gov Identifier:	NCT00365794 History of Changes
Other Study ID Numbers:	USC GCRC#1156
Study First Received:	August 16, 2006
Last Updated:	July 20, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Southern California:

Aging
Older men
Abdominal obesity

Central obesity
Insulin resistance
Low testosterone

Additional relevant MeSH terms:

Hypogonadism
Insulin Resistance
Obesity
Gonadal Disorders
Endocrine System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Testosterone

Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on February 09, 2012