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

NCT00365794 | Completed Phase 2 Results FDA Drug

• 1 other identifier: GCRC Protocol 1156
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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. 1.Supplemental testosterone will decrease abdominal adipose tissue and hepatic fat) and appendicular fat and intramyocellular lipid in peripheral muscles (IMCL).
2. 2.Supplemental testosterone will improve insulin sensitivity by:
3. 3.Decreasing hepatic glucose output (HGO), a measure of central insulin resistance
4. 4.increasing peipheral glucose disposal (Rd), a measure of periperal insuln sensiivity
5. 5.. Improving peripheral glucose disposal (Rd) by reducing IMCL
6. 6.Increasing appendicular skeletal muscle mass
7. 7.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).
8. 8.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)

Conditions

Aging; Obesity; Insulin Resistance; Hypogonadism

Keywords

Aging; Older men; Abdominal obesity; Central obesity; Insulin resistance; Low testosterone

Outcome Measures

Primary Outcomes (3)

• Change in Total Mass and Regional Adipose Adiposiy

  Change in total body mass, total fat mass, trunk fat, and extremity fat

  Baseline to 20 weeks

• Change in Hepatic Lipid

  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.

  Baseline to week 20

• Intramyocellular Lipid (IMCL)

  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

  Baseline to week 20

Secondary Outcomes (7)

• Change in Percentage of Total Body Fat

  Baseline and 20 weeks

• 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])

  Baseline and 20 weeks

• Change in Skeletal Muscle Mass by DEXA

  Baselne to 20 weeks

• Plasma Lipids

  Baseline to week 20

• Change in HOMA-IR

  Baseline to week 20

Study Arms (1)

Single arm

EXPERIMENTAL

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

Interventions

Topical testosterone gel 10 g/day DRUG

Testosterone gel therapy for 20 weeks

Also known as: Androgel

Single arm

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Entry Criteria:
• Men \> 60 years of age
• Total testosterone \< 300 ng/dL
• Waist circumference \>102 cm
• Fasting insulin level \> 18 U/L

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Southern California: lead
• Solvay Pharmaceuticals: collaborator

Study Sites (1)

LAC-USC Medical Center GCRC

Los Angeles, California, 90033, United States

Location

Related Publications (1)

• 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.

  PMID: 25392748 RESULT

MeSH Terms

Conditions

Obesity; Insulin Resistance; Hypogonadism; Obesity, Abdominal

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The primary limitation of this small pilot study is that it does not have a control group. It is also likely under-powered and thus unable to show significance differences for some measurements.

Results Point of Contact

• Title: Fred Sattler, MD
• Organization: University of Southern California

fsattler@usc.edu

323-409-4635

Study Officials

• Fred R Sattler, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No masking. This was an open label (un-blinded)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 16, 2006
• First Posted: August 17, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: August 26, 2019
• Results First Posted: August 26, 2019

Record last verified: 2019-08

Locations

US (1)