Diabetes Mellitus Type 2
Conditions
Keywords
DM type 2, Hypogonadism, Testosterone, AndroGel
Brief summary
This is to study the effect of replacing testosterone on different inflammatory cells in type 2 diabetics with low testosterone levels.
Detailed description
Type 2 diabetes is an atherosclerotic, pro-inflammatory and pro-oxidative stress. Hypogonadism( low testosterone) is also associated with increased levels of inflammatory mediators and atherosclerosis. This project is about studying the effect of testosterone replacement on different inflammatory cells in blood and urine. It will also compare the dose dependent effect on inflammatory cells. This also involves comparing level of inflammation in hypogonadic diabetic males treated with testosterone with those not treated with any replacement therapy. This study involves applying AndroGel for 8 wks and studying effects during this time and thereafter.
Interventions
Sponsors
Solvay Pharmaceuticals
University at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
35 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Males with age 35-75 years inclusive. * Evidence of hypogonadism: low free testosterone. * Type 2 Diabetes * People on stable doses of cholesterol lowering medications, blood pressure medications and multi-vitamins are allowed. * If currently on testosterone replacement,testosterone treatment will be held for 8 weeks. * BP under control even if on medication.
Exclusion criteria
* Coronary event or procedure in previous past 4 wks. * High PSA * H/O prostate cancer * Hepatic or renal disease * Participation in any other concurrent clinical trial * Any other life- threatening , non cardiac disease. * Uncontrolled BP * Congestive heart failure * High hemoglobin * Use of investigational agent or therapeutic regimen within 30 days of study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | 8 weeks | To measure the percent change from baseline at 8 weeks in Nuclear Factor kB DNA binding activity (in arbitrary units normalized to 100% at baseline) between AndroGel and Placebo using electrophoretic mobility shift assay (EMSA). Values at 8 weeks are converted to percent change and compared between the groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | 8 weeks | Comparison of relative percent change from baseline at 8 weeks in reactive oxygen species generation (measured as arbitrary units normalized to 100% at baseline) in mononuclear cells after either AndroGel or placebo using chemiluminescence PMSF activation assay. Values at 8 weeks are converted to percentage of the baseline and compared between the groups |
| Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | 8 week | To measure the relative percent change from baseline in the inflammatory mediator (CRP) at 8 weeks (values in ng/ml normalized to100% at baseline) following treatment with androgel compared to placebo. Values (in ng/ml) are converted to percentage of baseline at 8 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Androgel 5g androgel 5g
androgel: androgel 5g | 17 |
| Androgel 10g androgel 10g
androgel 10g: androgel 10g | 17 |
| Placebo placebo
placebo: placebo | 15 |
| Total | 49 |
Baseline characteristics
| Characteristic | Androgel 5g | Androgel 10g | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 14 Participants | 12 Participants | 39 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 8 | 57 years STANDARD_DEVIATION 9 | 59 years STANDARD_DEVIATION 9 | 58 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 17 Participants | 17 Participants | 15 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 15 |
| other Total, other adverse events | 0 / 17 | 0 / 17 | 0 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 15 |
Outcome results
Primary
Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo
To measure the percent change from baseline at 8 weeks in Nuclear Factor kB DNA binding activity (in arbitrary units normalized to 100% at baseline) between AndroGel and Placebo using electrophoretic mobility shift assay (EMSA). Values at 8 weeks are converted to percent change and compared between the groups
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Androgel 5g | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | baseline | 100 Percent change from baseline | Standard Deviation 0 |
| Androgel 5g | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | 8 week | 236 Percent change from baseline | Standard Deviation 197 |
| Androgel 10g | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | baseline | 100 Percent change from baseline | Standard Deviation 0 |
| Androgel 10g | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | 8 week | 82 Percent change from baseline | Standard Deviation 61 |
| Placebo | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | baseline | 100 Percent change from baseline | Standard Deviation 0 |
| Placebo | Effect of Androgel Treatment on Relative Nuclear Factor kB Activity Compared to Placebo | 8 week | 100 Percent change from baseline | Standard Deviation 103 |
Secondary
Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone
To measure the relative percent change from baseline in the inflammatory mediator (CRP) at 8 weeks (values in ng/ml normalized to100% at baseline) following treatment with androgel compared to placebo. Values (in ng/ml) are converted to percentage of baseline at 8 weeks.
Time frame: 8 week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Androgel 5g | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Androgel 5g | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | 8 week | 68 percentage of baseline value | Standard Deviation 9 |
| Androgel 10g | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Androgel 10g | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | 8 week | 130 percentage of baseline value | Standard Deviation 18 |
| Placebo | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Placebo | Change in Inflammatory Mediator C-Reactive Protein (CRP) Following Treatment With Testosterone | 8 week | 95 percentage of baseline value | Standard Deviation 10 |
Secondary
Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo
Comparison of relative percent change from baseline at 8 weeks in reactive oxygen species generation (measured as arbitrary units normalized to 100% at baseline) in mononuclear cells after either AndroGel or placebo using chemiluminescence PMSF activation assay. Values at 8 weeks are converted to percentage of the baseline and compared between the groups
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Androgel 5g | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Androgel 5g | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | 8 week | 91 percentage of baseline value | Standard Deviation 8 |
| Androgel 10g | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Androgel 10g | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | 8 week | 125 percentage of baseline value | Standard Deviation 17 |
| Placebo | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | baseline | 100 percentage of baseline value | Standard Deviation 0 |
| Placebo | Effect of Androgel Treatment on Reactive Oxygen Species Generation Compared to Placebo | 8 week | 110 percentage of baseline value | Standard Deviation 17 |