Effects of Testosterone Gel on Carbohydrate and Lipid Metabolism In Elderly Obese Men
Condition: Aging; Obesity; Insulin Resistance; Hypogonadism
MeSH terms: Obesity; Insulin Resistance; Hypogonadism
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Topical testosterone gel 10 g/day
Intervention type(s): Drug
Intervention description(s): Testosterone gel therapy for 20 weeks
Other intervention name(s): Androgel
Intervention MeSH terms: Testosterone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Aging; Older men; Abdominal obesity; Central obesity; Insulin resistance; Low testosterone