Hypogonadotropic Hypogonadism in Obese Young Males

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.

Study Overview

• Status: Terminated
• Conditions: Hypogonadism, Hypogonadotropic
• Intervention / Treatment: Drug: Clomiphene; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Obese males with hypogonadism-active; Subjects will be randomized to receive clomiphene capsules	Drug: Clomiphene; clomiphene capsule 25mg twice a week; Other Names: active
Placebo Comparator: Obese males with hypogonadism-placebo; Subjects will be randomized to receive placebo capsules	Drug: Placebo; placebo capsule 25mg twice a week
No Intervention: Obese males with normal testosterone; comparison group
No Intervention: lean males with normal testosterone; comparison group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Free Testosterone	after clomiphene or placebo treatment	12 weeks

Collaborators and Investigators

• Sponsor: Sandeep Singh Dhindsa, M.D., F.A.C.E

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): October 29, 2021
• Study Completion (Actual): October 29, 2021

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 7, 2017
• First Posted (Actual): August 10, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene
• Other Study ID Numbers: 28389

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No