Hypogonadotropic Hypogonadism in Obese Young Males

• Sponsor: Sandeep Singh Dhindsa, M.D., F.A.C.E (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03245827
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arms: 4
• Actual Duration (Months): 30.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism, Hypogonadotropic	Drug: Clomiphene; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Hypogonadotropic Hypogonadism in Obese Young Males
• Actual Study Start Date: Apr 1, 2019
• Actual Primary Completion Date: Oct 29, 2021
• Actual Study Completion Date: Oct 29, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Serum Free Testosterone [12 weeks]

   after clomiphene or placebo treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 30 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Louis Univeristy	Saint Louis	Missouri	United States	63104

Sponsors and Collaborators

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

Investigators

• Principal Investigator: sandeep dhindsa, md, St. Louis University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 2, 2020

More Information

Publications

None provided.

• Responsible Party: Sandeep Singh Dhindsa, M.D., F.A.C.E, Professor, St. Louis University
• ClinicalTrials.gov Identifier: NCT03245827
• Other Study ID Numbers: 28389
• First Posted: Aug 10, 2017
• Last Update Posted: Jun 29, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Hypogonadism; Clomiphene

Study Results

Participant Flow

Arm/Group Title	Obese Males With Hypogonadism-active	Obese Males With Hypogonadism-placebo	Obese Males With Normal Testosterone	Lean Males With Normal Testosterone
Arm/Group Description	Subjects will be randomized to receive clomiphene capsules Clomiphene: clomiphene capsule 25mg twice a week	Subjects will be randomized to receive placebo capsules Placebo: placebo capsule 25mg twice a week	comparison group	comparison group
Period Title: Overall Study
STARTED	1	0	3	5
COMPLETED	1	0	3	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Obese Males With Hypogonadism-active	Obese Males With Hypogonadism-placebo	Obese Males With Normal Testosterone	Lean Males With Normal Testosterone	Total
Arm/Group Description	Subjects will be randomized to receive clomiphene capsules Clomiphene: clomiphene capsule 25mg twice a week	Subjects will be randomized to receive placebo capsules Placebo: placebo capsule 25mg twice a week	comparison group	comparison group	Total of all reporting groups
Overall Participants	1	0	3	5	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22 (0)	28 (2)	21.8 (1.8)	23.9 (3.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN	0 0%	0 0%	0 0%
Male	1 100%	0 NaN	3 100%	5 100%	9 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 0%	0 0%	0 0%
Asian	0 0%	0 NaN	0 0%	2 40%	2 22.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 0%	0 0%	0 0%
Black or African American	0 0%	0 NaN	0 0%	0 0%	0 0%
White	1 100%	0 NaN	3 100%	3 60%	7 77.8%
More than one race	0 0%	0 NaN	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only one volunteer was randomized.

Arm/Group Title	Obese Males With Hypogonadism-active	Obese Males With Hypogonadism-placebo
Arm/Group Description	Subjects will be randomized to receive clomiphene capsules Clomiphene: clomiphene capsule 25mg twice a week	Subjects will be randomized to receive placebo capsules Placebo: placebo capsule 25mg twice a week
Measure Participants	1	0
Mean (Standard Deviation) [pg/ml]	85 (NA)

Adverse Events

Time Frame	3 months
Adverse Event Reporting Description	no subjects were recruited in placebo group
Arm/Group Title	Obese Males With Hypogonadism-active		Obese Males With Hypogonadism-placebo		Obese Males With Normal Testosterone		Lean Males With Normal Testosterone
Arm/Group Description	Subjects will be randomized to receive clomiphene capsules Clomiphene: clomiphene capsule 25mg twice a week		Subjects will be randomized to receive placebo capsules Placebo: placebo capsule 25mg twice a week		comparison group		comparison group
All Cause Mortality
	Obese Males With Hypogonadism-active		Obese Males With Hypogonadism-placebo		Obese Males With Normal Testosterone		Lean Males With Normal Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/3 (0%)		0/5 (0%)
Serious Adverse Events
	Obese Males With Hypogonadism-active		Obese Males With Hypogonadism-placebo		Obese Males With Normal Testosterone		Lean Males With Normal Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/3 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Obese Males With Hypogonadism-active		Obese Males With Hypogonadism-placebo		Obese Males With Normal Testosterone		Lean Males With Normal Testosterone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/3 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.