Clinical trial NCT00365794: Effects of Testosterone Gel on Carbohydrate and Lipid Metabolism In Elderly Obese Men
Official title: Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aging
Obesity
Insulin Resistance
Hypogonadism
Keywords: Aging
Older men
Abdominal obesity
Central obesity
Insulin resistance
Low testosterone
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Solvay Pharmaceuticals
First posted: 2006-08-17
Enrollment: 22
Sex: MALE
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 adipose tissue and hepatic fat) and appendicular 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. increasing peipheral glucose disposal (Rd), a measure of periperal insuln sensiivity
   3. . Improving peripheral glucose disposal (Rd) by reducing IMCL
   4. Increasing appendicular skeletal muscle mass

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 and hepatic fat) and peripheral skeletal muscle fat (appendicular fat and IMCL).
2. Secondary Objectives: To determine the effects of supplemental testosterone to achieve testosterone levels in the upper normal physiologic range:on central insulin sensitivity ( hepatic glucose output (\[HGO\]) and peripheral insulin sensitivity (glucose disposal (Rd)

Results of this study will provide greater understanding whether androgen therapy enhances insulin sensitivity by decreasing HGO, improving peripheral Rd and if these desired effects are achieved, whether they are due to reductions in abdominal fat or liver lipid, 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.

Detailed description: Study Design: This is an investigator-initiated open label, study to investigate the effects of supplemental testosterone (gel formulation) 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 DEXA measures of abdominal and appendicular fat mass and hepatic fat, and IMCL will be quantified by 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) at 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 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

Primary outcomes:
measure: Change in Total Mass and Regional Adipose Adiposiy
timeFrame: Baseline to 20 weeks
measure: Change in Hepatic Lipid
timeFrame: Baseline to week 20
measure: Intramyocellular Lipid (IMCL)
timeFrame: Baseline to week 20
Secondary outcomes:
measure: Change in Percentage of Total Body Fat
timeFrame: Baseline and 20 weeks
measure: Change in 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])
timeFrame: Baseline and 20 weeks
measure: Change in Skeletal Muscle Mass by DEXA
timeFrame: Baselne to 20 weeks
measure: Plasma Lipids
timeFrame: Baseline to week 20
measure: Change in HOMA-IR
timeFrame: Baseline to week 20
measure: Change in Basal FFAs in Plasma
timeFrame: Baseline to week 20
measure: Change in Plasma Free Fatty Acids During Glucose Clamp
timeFrame: Baseline to 20 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC-USC Medical Center GCRC
state: California
Study officials:
affiliation: University of Southern California
name: Fred R Sattler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sattler F, He J, Chukwuneke J, Kim H, Stewart Y, Colletti P, Yarasheski K, Buchanan T. Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some Older Men with Abdominal Obesity. J Gerontol Geriatr Res. 2014 Jun 7;3(3):1000159. doi: 10.4172/2167-7182.1000159.