Trial Outcomes & Findings for Effects of Testosterone Gel on Carbohydrate and Lipid Metabolism In Elderly Obese Men (NCT NCT00365794)

NCT ID: NCT00365794

Last Updated: 2019-08-26

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: Baseline to week 20
• Results posted on: 2019-08-26

Participant Flow

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.

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.

Participant milestones

Measure	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
Overall Study STARTED	22
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	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
Overall Study Withdrawal by Subject	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Single Arm n=20 Participants open label treatment with testosterone gel
Age, Continuous	67.5 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
AM total testosterone level	10.6 nmoles/liter n=5 Participants
waist circumference	114 centimeters n=5 Participants
blood panels total cholesterol	4.61 mmole/liter n=5 Participants
blood panels LDL cholesterol	3.11 mmole/liter n=5 Participants
blood panels HDL cholesterol	1.06 mmole/liter n=5 Participants
blood panels Fasting triglycerides	1.59 mmole/liter n=5 Participants
Patient history at enrollment Family history of diabetes	4 Participants n=5 Participants
Patient history at enrollment Smoking ever	14 Participants n=5 Participants
Patient history at enrollment Smoking currently	0 Participants n=5 Participants
Patient history at enrollment On Rx for lipid disorder	12 Participants n=5 Participants
Patient history at enrollment On Rx for hypertension	10 Participants n=5 Participants
Body compotion Total body mass	104.5 kilograms n=5 Participants
Body compotion Total fat mass	34.6 kilograms n=5 Participants
Body compotion Trunk fat mass	19.3 kilograms n=5 Participants
Body compotion Extremity fat mass	12.9 kilograms n=5 Participants
Body compotion Total lean body mss	64.3 kilograms n=5 Participants
Body compotion Extremity lean mass	29.1 kilograms n=5 Participants
Percentage of body fat	31.5 percentage n=5 Participants
Insulin senstivity Whole body insulin sensivity	2.93 dL/min per μU/mL; n=5 Participants
Insulin senstivity Hepatic glucose output	2.89 dL/min per μU/mL; n=5 Participants
Insulin senstivity Rate of glucose disposal	2.93 dL/min per μU/mL; n=5 Participants
HOMA-IR	3.55 microU/L) x fasting glucose (nmol/L)/22. n=5 Participants
Basal free fatty acids	0.35 mEq/L n=5 Participants
Change in glucose clamp free fatty acids over 0 to 4 hours	0.30 grams n=5 Participants
Hepatic lipid	0.11 ratio n=5 Participants
Intramyocellular lipid (IMCL)	5.8 ratio n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 20 weeks

Population: Data for one participant was not available

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

Outcome measures

Measure	Single Arm n=19 Participants 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
Change in Total Mass and Regional Adipose Adiposiy Total body mass	0.3 kilograms Interval -4.8 to 4.1
Change in Total Mass and Regional Adipose Adiposiy Total fat mass	-1.4 kilograms Interval -7.4 to 2.0
Change in Total Mass and Regional Adipose Adiposiy Trunk fat mass	-0.9 kilograms Interval -4.6 to 0.2
Change in Total Mass and Regional Adipose Adiposiy Extremity fat mass	-0.7 kilograms Interval -3.0 to 2.3

PRIMARY outcome

Timeframe: Baseline to week 20

Population: Data not available for one subject

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.

Outcome measures

Measure	Single Arm n=19 Participants 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
Change in Hepatic Lipid	-36 ratio Interval -84.0 to 127.0

PRIMARY outcome

Timeframe: Baseline to week 20

Population: data not available for 5 subjects

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

Outcome measures

Measure	Single Arm n=15 Participants 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
Intramyocellular Lipid (IMCL)	-30 ratio Interval -85.0 to 43.0

SECONDARY outcome

Timeframe: Baseline and 20 weeks

Population: Data not available for one subject

Percentage of total body fat is quantified by DEXA scanning

Outcome measures

Measure	Single Arm n=19 Participants 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
Change in Percentage of Total Body Fat	-1.6 percentage of total body fat Interval -6.5 to 0.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Single Arm n=20 Participants 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
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]) Whole body insulin sensitiity	1.05 dL/min per μU/mL Interval -2.44 to 3.73
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]) hepaic glucose output (HGO)	-0.16 dL/min per μU/mL Interval -2.58 to 7.49
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]) peripheral glucose disposal (Rd)	1.16 dL/min per μU/mL Interval -3.08 to 3.85

SECONDARY outcome

Timeframe: Baselne to 20 weeks

Skeletal muscle mass was assesed by regional DEXA to quantify appendicular lean tissues which is primarily muscle.

Outcome measures

Measure	Single Arm n=20 Participants 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
Change in Skeletal Muscle Mass by DEXA	1.2 kilograms Interval -1.1 to 4.8

SECONDARY outcome

Timeframe: Baseline to week 20

Outcome measures

Measure	Single Arm n=20 Participants 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
Plasma Lipids Fasting triglycerides	-0.33 mg/dL Interval -2.7 to 0.43
Plasma Lipids Total cholesterol	-0.52 mg/dL Interval -1.74 to 0.88
Plasma Lipids LDL cholesterol	-0.23 mg/dL Interval -1.45 to 0.7
Plasma Lipids HDL cholesterol	-0.10 mg/dL Interval -0.6 to 0.05

SECONDARY outcome

Timeframe: Baseline to week 20

HOMA-IR is a measure of insulin resistance

Outcome measures

Measure	Single Arm n=20 Participants 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
Change in HOMA-IR	-0.75 microU/L) x fasting glucose (nmol/L)/22 Interval -6.94 to 4.18

SECONDARY outcome

Timeframe: Baseline to week 20

FFA (plasma free fatty acids) are measure of lipid metabolism

Outcome measures

Measure	Single Arm n=20 Participants 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
Change in Basal FFAs in Plasma	-0.1 mEq/L Interval -0.22 to 0.21

SECONDARY outcome

Timeframe: Baseline to 20 weeks

Outcome measures

Measure	Single Arm n=20 Participants 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
Change in Plasma Free Fatty Acids During Glucose Clamp	-0.1 grams Interval -0.12 to 0.17

Adverse Events

Open Label Testosterone Treatment

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Open Label Testosterone Treatment n=20 participants at risk No serious adverse events occurred PSA and Framingham CV Disease Risk Score did not increase
Skin and subcutaneous tissue disorders Skin irritation	5.0% 1/20 • Number of events 1 • 20 weeks for each participant No serious adverse events occurred.

Additional Information

Fred Sattler, MD

University of Southern California

Phone: 323-409-4635

Email: fsattler@usc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place