Hypogonadism, Hypogonadotropic
Conditions
Brief summary
Obesity can lead to low testosterone concentrations in young men. This study will study the effects of low testosterone in those men and the result of treating them with clomiphene.
Detailed description
The prevalence of obesity has increased in children over the past few decades. Approximately 20% of adolescent boys are now considered obese. It is well accepted that obese children are at increased risk for high blood pressure, lipid abnormalities and type 2 diabetes. Recent studies have uncovered yet another undesirable effect of obesity. The testosterone levels of obese boys are only half those of lean boys at completion of puberty. Testosterone is important for muscle and bone development. Men with low testosterone are at higher risk of insulin resistance and inflammation, which lead to type 2 diabetes and heart disease. Since testosterone is the major reproductive hormone, these obese boys are at risk of decreased fertility. Men are supposed to achieve their peak testosterone levels at puberty. Thereafter, there is a decline in testosterone levels at the rate of 2% per year for the rest of life. Thus there is a clear need to develop a deeper understanding of low testosterone in these males who are entering their peak fertility years. There are no approved treatments for this disorder. The investigators propose to conduct a randomized placebo controlled trial to evaluate the effect of treatment with clomiphene in obese young men(age 18-30 years) who have low testosterone concentrations. Clomiphene is a drug that increases testosterone concentrations and possibly increases sperm production. In contrast, testosterone replacement therapy decreased fertility and cannot be used in young men. Investigators will study the effect of treatment with clomiphene or placebo tablets for 12 weeks in 30 subjects. The study will evaluate:- 1. testicular function: Testosterone and two proteins secreted by testis(insulin like factor 3 and inhibin B) will be measured in the blood before and after treatment with clomiphene or placebo. 2. insulin resistance: Investigators will measure insulin and glucose levels in the blood. 3. inflammation: Investigators will measure proteins that induce inflammation.
Interventions
DRUGClomiphene
clomiphene capsule 25mg twice a week
DRUGPlacebo
placebo capsule 25mg twice a week
Sponsors
Sandeep Singh Dhindsa, M.D., F.A.C.E
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Males * Age 18-30 years inclusive will be recruited. A total of 90 males will be recruited:- * 30 obese males (defined as BMI ≥30 kg/m2) with HH, * 30 obese males with normal FT concentrations and * 30 lean males (defined as BMI \<25 kg/m2) with normal FT concentrations.
Exclusion criteria
* Use of androgens, clomiphene, hCG, aromatase inhibitors or over the counter health supplements which contain androgens currently or in the past 6 months * Hematocrit \> 50% * Congestive heart failure * currently suffering from depression * type 1 diabetes * Hepatic disease (transaminase \> 3 times normal) or cirrhosis * Renal impairment (eGFR\<30 ml/min/1.73m2) * HIV or Hepatitis C positive status * Participation in any other concurrent clinical trial * currently suffering from foot ulcer, significant periodontal disease or any other chronic infectious condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Free Testosterone | 12 weeks | after clomiphene or placebo treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obese Males With Hypogonadism-active Subjects will be randomized to receive clomiphene capsules
Clomiphene: clomiphene capsule 25mg twice a week | 1 |
| Obese Males With Hypogonadism-placebo Subjects will be randomized to receive placebo capsules
Placebo: placebo capsule 25mg twice a week | 0 |
| Obese Males With Normal Testosterone comparison group | 3 |
| Lean Males With Normal Testosterone comparison group | 5 |
| Total | 9 |
Baseline characteristics
| Characteristic | Obese Males With Hypogonadism-active | Total | Lean Males With Normal Testosterone | Obese Males With Normal Testosterone | Obese Males With Hypogonadism-placebo |
|---|---|---|---|---|---|
| Age, Continuous | 22 years STANDARD_DEVIATION 0 | 23.9 years STANDARD_DEVIATION 3.5 | 21.8 years STANDARD_DEVIATION 1.8 | 28 years STANDARD_DEVIATION 2 | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 7 Participants | 3 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 9 Participants | 5 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 1 | 0 / 0 | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 | 0 / 3 | 0 / 5 |
Outcome results
Primary
Serum Free Testosterone
after clomiphene or placebo treatment
Time frame: 12 weeks
Population: Only one volunteer was randomized.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Obese Males With Hypogonadism-active | Serum Free Testosterone | 85 pg/ml |