Hypogonadotropic Hypogonadism in Obese Young Males

Sandeep Singh Dhindsa, M.D., F.A.C.E

Status and phase: Terminated; Phase 2

Conditions: Hypogonadism, Hypogonadotropic

Treatments: Drug: Placebo; Drug: Clomiphene

Study type: Interventional

Funder types: Other

Identifiers

NCT03245827

28389

Details and patient eligibility

About

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.

Full 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.

Enrollment: 9 patients

Sex: Male

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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9 participants in 4 patient groups, including a placebo group

Obese males with hypogonadism-active

Active Comparator group

Description:

Subjects will be randomized to receive clomiphene capsules

Treatment:

Drug: Clomiphene

Obese males with hypogonadism-placebo

Placebo Comparator group

Description:

Subjects will be randomized to receive placebo capsules

Treatment:

Drug: Placebo

Obese males with normal testosterone

No Intervention group

Description:

comparison group

lean males with normal testosterone

No Intervention group

Description:

comparison group