Body Composition in Infants With Klinefelter Syndrome and Effects of Testosterone Treatment

This research study in infant males with Klinefelter syndrome (47,XXY) will learn more about body composition (muscle and fat) and male hormones and look at the effect of testosterone shots on body composition. The Investigators know that older boys and men with Klinefelter syndrome often have more fat compared to muscle than adults without Klinefelter syndrome, but we do not know if this difference is present at birth or develops over time. The Investigators will learn if body composition and motor skills are improved with testosterone treatment in infants with Klinefelter syndrome.

Study Overview

• Status: Completed
• Conditions: Klinefelter Syndrome
• Intervention / Treatment: Drug: testosterone cypionate 200mg/ml

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male infants with 47,XXY karyotype

Exclusion Criteria:

• Gestational age at birth <36 weeks
• Birth weight <5%ile or >95% for gestational age
• History of thrombosis in a first degree relative
• Exposure to androgen therapy outside of the study protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Testosterone treatment; Testosterone cypionate (200 mg/ml) intramuscular injection	Drug: testosterone cypionate 200mg/ml; Subjects in this group will be randomized to receive testosterone cypionate 200 mg/ml to be given intramuscularly every 4 weeks for a total of 3 doses.
No Intervention: No treatment; Subjects will not receive any testosterone during the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Fat Percent Z-score	Body fat percentage will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period. Age and sex-normed z-scores will be calculated. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Change in the z-score over time, if following a normal growth curve, is 0. Positive change in z-scores indicates a gain in body fat above growth typically expected. Negative change in z-scores indicates a gain in body fat that is less than typically expected.	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Luteinizing Hormone (LH)	Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.	baseline only
Serum Follicle Stimulating Hormone (FSH)	Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.	baseline only
Serum Total Testosterone	Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured.	baseline only
Serum Inhibin B (INHB)	Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured.	baseline only
Serum Anti-Mullerian Hormone (AMH)	Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.	baseline only
Leptin	Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.	baseline only
Change in Raw Score on the Alberta Infant Motor Scale	Muscle tone and motor development will be assessed by an occupational therapist using the standardized Alberta Infant Motor Scale (AIMS). The AIMS scale measures infant motor maturation from birth until the age of independent walking. An occupational therapists assesses 58 motor behavior items in 4 position categories: prone (21 items), supine (9 items), sitting (12 items) & standing(16 standing). Each item receives one point (range of raw scores 0-58), with higher scores indicating more skills acquired. For change in scores, the raw score at 3 months was subtracted from the baseline raw score.	3 months
Change in Score on the Movement Assessment of Infants (MAI)	Muscle tone and motor development will be assessed by an occupational therapist using the standardized Movement Assessment of Infants (MAI). The MAI evaluates four domains: muscle tone, primitive reflex, automatic reactions and volitional movement. All items are scored 1-5 and summed to generate a "Total Risk Score". Lower scores indicate better function, and Total Risk Scores of 8 or more indicate high risk.	3 months
Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2	Motor development will be assessed by an occupational therapist using the standardized Peabody Developmental Motor Scales 2. Standard scores are normalized to age with a mean of 100 and standard deviation of 15. Change in standard score was calculated as the differences between the subject's standard score at 3 months minus the standard score at baseline. A positive change in standard scores would indicate greater growth on the measure relative to peers, while a negative number would indicate slower growth on the measure relative to peers.	3 months
Change in Penile Length	Stretched penile length will be measured by a physician before randomization and at the end of the study period.	Baseline and 3 months
Change in Fat Free Mass	Fat free mass (lean mass) will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period.	Baseline and 3 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Shanlee M Davis, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2015
• Primary Completion (Actual): January 31, 2018
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: March 31, 2015
• First Submitted That Met QC Criteria: March 31, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: body composition; Klinefelter syndrome; XXY; sex chromosome variation; sex chromsome aneuploidy
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Hypogonadism; Syndrome; Klinefelter Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 14-1720; UL1TR001082 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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