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Effects of Testosterone Gel on Carbohydrate and Lipid Metabolism In Elderly Obese Men

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ClinicalTrials.gov Identifier: NCT00365794
Recruitment Status : Completed
First Posted : August 17, 2006
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
Solvay Pharmaceuticals
Information provided by (Responsible Party):
Fred Sattler, MD, University of Southern California

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.


Condition or disease Intervention/treatment Phase
Aging Obesity Insulin Resistance Hypogonadism Drug: Topical testosterone gel 10 g/day Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: No masking. This was an open label (un-blinded)
Primary Purpose: Treatment
Official Title: Investigator Initiated Study of the Effects of Androgen Therapy on Carbohydrate and Lipid Metabolism In Elderly Men
Study Start Date : August 2006
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Single arm
Open label treatment without masking with each participant serving as his own control. Measurements are compared before and after treatment.
Drug: Topical testosterone gel 10 g/day
Testosterone gel therapy for 20 weeks
Other Name: Androgel




Primary Outcome Measures :
  1. Change in Total Mass and Regional Adipose Adiposiy [ Time Frame: Baseline to 20 weeks ]
    Change in total body mass, total fat mass, trunk fat, and extremity fat

  2. Change in Hepatic Lipid [ Time Frame: Baseline to week 20 ]
    Amount of liver fat is highly predictive of insulin resistance. Hepatic fat is measured by MR spectroscopy and adjusted for H2O and results are reported as ratio of these two.

  3. Intramyocellular Lipid (IMCL) [ Time Frame: Baseline to week 20 ]
    IMCL is quantified by MR spectroscopy of the anterior tibialis muscle of the leg. The value is adjusted for creatine and reported as a ratio


Secondary Outcome Measures :
  1. Change in Percentage of Total Body Fat [ Time Frame: Baseline and 20 weeks ]
    Percentage of total body fat is quantified by DEXA scanning

  2. 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]) [ Time Frame: Baseline and 20 weeks ]
    In the final analysis, total and regional carbohydrate metabolism during a 2-hr hyperinsulinemic euglycemic clamp (peripheral glucose disposal [Rd],hepatic glucose output [HGO]) were analyzed by mass transfer of glucose during both stages of the clamp relative to insulin levels.

  3. Change in Skeletal Muscle Mass by DEXA [ Time Frame: Baselne to 20 weeks ]
    Skeletal muscle mass was assesed by regional DEXA to quantify appendicular lean tissues which is primarily muscle.

  4. Plasma Lipids [ Time Frame: Baseline to week 20 ]
  5. Change in HOMA-IR [ Time Frame: Baseline to week 20 ]
    HOMA-IR is a measure of insulin resistance

  6. Change in Basal FFAs in Plasma [ Time Frame: Baseline to week 20 ]
    FFA (plasma free fatty acids) are measure of lipid metabolism

  7. Change in Plasma Free Fatty Acids During Glucose Clamp [ Time Frame: Baseline to 20 weeks ]


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Ages Eligible for Study:   60 Years to 90 Years   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00365794


Locations
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United States, California
LAC-USC Medical Center GCRC
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
Solvay Pharmaceuticals
Investigators
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Principal Investigator: Fred R Sattler, MD University of Southern California

Publications of Results:
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Responsible Party: Fred Sattler, MD, Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT00365794     History of Changes
Other Study ID Numbers: GCRC Protocol 1156
First Posted: August 17, 2006    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: August 26, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fred Sattler, MD, University of Southern California:
Aging
Older men
Abdominal obesity
Central obesity
Insulin resistance
Low testosterone
Additional relevant MeSH terms:
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Obesity
Insulin Resistance
Hypogonadism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Gonadal Disorders
Endocrine System Diseases
Methyltestosterone
Testosterone
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents