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

• ClinicalTrials.gov Identifier: NCT02408445
• Recruitment Status: Completed
• First Posted: April 3, 2015
• Results First Posted: April 15, 2020
• Last Update Posted: April 15, 2020
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Klinefelter Syndrome	Drug: testosterone cypionate 200mg/ml	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Body Composition in Infants With Klinefelter Syndrome and Effects of Testosterone Treatment
• Actual Study Start Date: May 8, 2015
• Actual Primary Completion Date: January 31, 2018
• Actual Study Completion Date: January 1, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change in Body Fat Percent Z-score [ Time Frame: Baseline and 3 months ]
   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.

Secondary Outcome Measures :

1. Serum Luteinizing Hormone (LH) [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. Ultrasensitive LH will be measured.
2. Serum Follicle Stimulating Hormone (FSH) [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. Ultrasensitive FSH will be measured.
3. Serum Total Testosterone [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. Total testosterone by mass spectroscopy will be measured.
4. Serum Inhibin B (INHB) [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. Inhibin B levels will be measured.
5. Serum Anti-Mullerian Hormone (AMH) [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. AMH levels will be measured.
6. Leptin [ Time Frame: baseline only ]
   Serum will be collected at the first study visit prior to randomization. Leptin levels will be measured.
7. Change in Raw Score on the Alberta Infant Motor Scale [ Time Frame: 3 months ]
   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.
8. Change in Score on the Movement Assessment of Infants (MAI) [ Time Frame: 3 months ]
   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.
9. Change in Total Motor Standard Score on the Peabody Developmental Motor Scales 2 [ Time Frame: 3 months ]
   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.
10. Change in Penile Length [ Time Frame: Baseline and 3 months ]
    Stretched penile length will be measured by a physician before randomization and at the end of the study period.
11. Change in Fat Free Mass [ Time Frame: Baseline and 3 months ]
    Fat free mass (lean mass) will be measured using air displacement plethysmography (PEA POD) at the beginning and end of the study period.

Eligibility Criteria

• Ages Eligible for Study: 42 Days to 108 Days (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

Investigators

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

  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:

Study Protocol and Statistical Analysis Plan  [PDF] March 9, 2015

Informed Consent Form  [PDF] February 12, 2016

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02408445
• Other Study ID Numbers: 14-1720; UL1TR001082 ( U.S. NIH Grant/Contract )
• First Posted: April 3, 2015
• Results First Posted: April 15, 2020
• Last Update Posted: April 15, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:

body composition; Klinefelter syndrome; XXY; sex chromosome variation; sex chromsome aneuploidy

Additional relevant MeSH terms:

Klinefelter Syndrome; Syndrome; Disease; Pathologic Processes; Sex Chromosome Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents