Hypogonadotropic Hypogonadism, Type 2 Diabetes
Conditions
Keywords
hypogonadism, diabetes, spermatogenesis, insulin resistance
Brief summary
Low testosterone production, known clinically as hypogonadism, appears to be common complication of type 2 diabetes, affecting one in three diabetic men. Hypogonadism is known to be associated with decreased muscle mass, increased fat mass, increased inflammation and decreased fertility. In this grant, the investigators propose to study the effects of having low testosterone on 1) insulin sensitivity, the ability of the body to handle glucose 2) fat and muscle mass at specific areas of the body 3) expression of mediators of inflammation in the blood 4) semen quality. This study will compare diabetic men (with or without hypogonadism). This study will also evaluate the effect of treatment with clomiphene (a drug that increases testosterone and sperm production) or testosterone in men with diabetes and hypogonadism. The investigators hope that this project will help us understand the state of hypogonadism in young type 2 diabetic men who are in their peak fertility years and give us insights into treatment of this condition. With the rising prevalence of type 2 diabetes in the young, this project may have implications for public health.
Detailed description
This project will study young men with type 2 diabetes. We have shown that half of these men have low testosterone levels. This can lead to 1) Low muscle mass; 2) more fat mass; 3) insulin resistance; 4) low sperm count and 5) increased inflammation (that increases the risk of heart disease). This project will study these consequences in detail and also the possibility of reversing them with treatment. Information from this project will be useful in planning of future studies that will evaluate the effect of treatment of low testosterone on mortality, heart disease and stroke.
Interventions
DRUGtestosterone
intramuscular every 2 weeks
DRUGclomiphene
thrice a week
DRUGplacebo
intramuscular saline injections every 2 weeks
Sponsors
American Diabetes Association
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* T2D Males with age 18-40 years
Exclusion criteria
1. planning to have children in the next one year 2. Use of androgens, CC, hCG, aromatase inhibitors or over the counter health supplements which contain androgens currently or in the past 6 months; 3. PSA \> 4ng/ml, symptoms of severe BPH, prostate nodule or severe enlargement on digital rectal examination or h/o prostatic carcinoma 4. Hemoglobin A1c \> 8% 5. Hematocrit \> 50% 6. History of obstructive sleep apnea 7. Congestive heart failure 8. Use of thiazolidinediones or exenatide 9. currently suffering from depression, with or without treatment 10. history of severe depression in the past which needed hospitalization 11. currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition 12. Coronary event or procedure in the previous 6 months 13. Hepatic disease (transaminase \> 3 times normal) or cirrhosis 14. Renal impairment (serum creatinine \> 1.5) 15. HIV or Hepatitis C positive status 16. Participation in any other concurrent clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Resistance | 6 months | To compare the insulin sensitivity as measured by whole body glucose uptake during hyperinsulinemic euglycemic (HE) clamp in young T2D men with and without HH. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone intramuscular injections every 2 weeks
testosterone: intramuscular every 2 weeks | 1 |
| Clomiphene oral drug thrice a week
clomiphene: thrice a week | 1 |
| Placebo for Testosterone placebo for testosterone arm
placebo: intramuscular saline injections every 2 weeks | 0 |
| Placebo for Clomiphene oral placebo for clomiphene arm
placebo: oral | 0 |
| Eugonadal Obese obese men with normal testosterone level | 1 |
| Lean healthy lean men (control) | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | Testosterone | Clomiphene | Eugonadal Obese | Lean | Total | Placebo for Testosterone | Placebo for Clomiphene |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 0 | 30 years STANDARD_DEVIATION 0 | 36 years STANDARD_DEVIATION 0 | 21 years STANDARD_DEVIATION 1 | 30 years STANDARD_DEVIATION 7 | — | — |
| Region of Enrollment United States | 1 participants | 1 participants | 1 participants | 2 participants | 5 participants | — | — |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 2 |
Outcome results
Primary
Insulin Resistance
To compare the insulin sensitivity as measured by whole body glucose uptake during hyperinsulinemic euglycemic (HE) clamp in young T2D men with and without HH.
Time frame: 6 months
Population: study terminated