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| Name | Class |
|---|---|
| Solvay Pharmaceuticals | INDUSTRY |
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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 adipose tissue and hepatic fat) and appendicular fat and intramyocellular lipid in peripheral muscles (IMCL).
Supplemental testosterone will improve insulin sensitivity by:
B. OBJECTIVES:
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.
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.
All components of the study will be conducted in the USC NIH-funded (NCRR), General Clinical Research Center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm | Experimental | Open label treatment without masking with each participant serving as his own control. Measurements are compared before and after treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topical testosterone gel 10 g/day | Drug | Testosterone gel therapy for 20 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percentage of Total Body Fat | Percentage of total body fat is quantified by DEXA scanning | 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]) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fred R Sattler, MD | University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LAC-USC Medical Center GCRC | Los Angeles | California | 90033 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25392748 | Result | 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. |
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Consenting subjects were evaluated for eligibility and had to be:
Men 60 years-or-older, with morning testosterone <400ng/dL, waist circumference ≥102cm, and evidence of insulin resistance; HgbA1c of 5.7-6.4% [20] or HOMA-IR ≥4.0. Exclusion criteria included diabetes, PSA ≥4.0μg/L, hct ≥50%, AST ≥2X ULN, concurrent inflammatory condition.
Potential subjects were primarily recruited from 2011 to 2013 and were evaluated and studied at the University of Southern California CTSI Clinical Trials Unit. 22 subjects met all eligibility requirements and begun study therapy with testosterone gel. Two did not complete treatment. Thus, 20 completed all evaluations as planned.
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| ID | Title | Description |
|---|---|---|
| FG000 | Single Arm | Open label treatment with each participant serving as his own control. Data is compared before and after treatment. Topical testosterone (Androgel) 10 g/day: Testosterone therapy for 20 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Single Arm | open label treatment with testosterone gel |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Total Mass and Regional Adipose Adiposiy | Change in total body mass, total fat mass, trunk fat, and extremity fat | Data for one participant was not available | Posted | Median | Full Range | kilograms | Baseline to 20 weeks |
|
|
20 weeks for each participant
No serious adverse events occurred.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open Label Testosterone Treatment | No serious adverse events occurred PSA and Framingham CV Disease Risk Score did not increase |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin irritation | Skin and subcutaneous tissue disorders | ACTG | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fred Sattler, MD | University of Southern California | 323-409-4635 | fsattler@usc.edu |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D007006 | Hypogonadism |
| D056128 | Obesity, Abdominal |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D013739 | Testosterone |
| ID | Term |
|---|---|
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 |
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No masking. This was an open label (un-blinded)
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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. |
| Baseline and 20 weeks |
| Change in Skeletal Muscle Mass by DEXA | Skeletal muscle mass was assesed by regional DEXA to quantify appendicular lean tissues which is primarily muscle. | Baselne to 20 weeks |
| Plasma Lipids | Baseline to week 20 |
| Change in HOMA-IR | HOMA-IR is a measure of insulin resistance | Baseline to week 20 |
| Change in Basal FFAs in Plasma | FFA (plasma free fatty acids) are measure of lipid metabolism | Baseline to week 20 |
| Change in Plasma Free Fatty Acids During Glucose Clamp | Baseline to 20 weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| AM total testosterone level | Median | Full Range | nmoles/liter |
|
| waist circumference | Median | Full Range | centimeters |
|
| blood panels | Median | Full Range | mmole/liter |
|
| Patient history at enrollment | Count of Participants | Participants |
|
| Body compotion | kilograms as measured by DEXA | Median | Full Range | kilograms |
|
| Percentage of body fat | Median | Full Range | percentage |
|
| Insulin senstivity | Median | Full Range | dL/min per μU/mL; |
|
| HOMA-IR | Median | Full Range | microU/L) x fasting glucose (nmol/L)/22. |
|
| Basal free fatty acids | Median | Full Range | mEq/L |
|
| Change in glucose clamp free fatty acids over 0 to 4 hours | Median | Full Range | grams |
|
| Hepatic lipid | Measurement is adjusted for water content and commonly reported as ratio | Median | Full Range | ratio |
|
| Intramyocellular lipid (IMCL) | IMCL is commonly adjusted for creatine (Cr) content and reported as a raio | Median | Full Range | ratio |
|
|
|
| Primary | 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. | Data not available for one subject | Posted | Median | Full Range | ratio | Baseline to week 20 |
|
|
|
|
| Primary | 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 | data not available for 5 subjects | Posted | Median | Full Range | ratio | Baseline to week 20 |
|
|
|
|
| Secondary | Change in Percentage of Total Body Fat | Percentage of total body fat is quantified by DEXA scanning | Data not available for one subject | Posted | Median | Full Range | percentage of total body fat | Baseline and 20 weeks |
|
|
|
|
| Secondary | 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]) | 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. | Posted | Median | Full Range | dL/min per μU/mL | Baseline and 20 weeks |
|
|
|
|
| Secondary | Change in Skeletal Muscle Mass by DEXA | Skeletal muscle mass was assesed by regional DEXA to quantify appendicular lean tissues which is primarily muscle. | Posted | Median | Full Range | kilograms | Baselne to 20 weeks |
|
|
|
|
| Secondary | Plasma Lipids | Posted | Median | Full Range | mg/dL | Baseline to week 20 |
|
|
|
|
| Secondary | Change in HOMA-IR | HOMA-IR is a measure of insulin resistance | Posted | Median | Full Range | microU/L) x fasting glucose (nmol/L)/22 | Baseline to week 20 |
|
|
|
|
| Secondary | Change in Basal FFAs in Plasma | FFA (plasma free fatty acids) are measure of lipid metabolism | Posted | Median | Full Range | mEq/L | Baseline to week 20 |
|
|
|
|
| Secondary | Change in Plasma Free Fatty Acids During Glucose Clamp | Posted | Median | Full Range | grams | Baseline to 20 weeks |
|
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 1 |
| 20 |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
|
| t-test, 2 sided |
| 0.59 |
| Other |
| Statistical analysis for change in rate of peripheral glucose disposal (test of peripheral insulin sensitivity) after treatment with testosterone gel for 20 weeks | t-test, 2 sided | 0.03 | Other |
| t-test, 2 sided |
| 0.004 |
| Other |
Test for total cholesterol |
| nts A change in 20 plasma lipids (fasting triglycerides and lipid fractions) after 20 weeks of treatment with testosterone gel | t-test, 2 sided | .02 | Other | Test for LDL cholesterol |
| A change in 20 plasma lipids (fasting triglycerides and lipid fractions) after 20 weeks of treatment with testosterone gel | t-test, 2 sided | 0.004 | Other | Test for HDL cholesterol |