Effect of Growth Hormone on Early Brain Development in Girls With Turner Syndrome

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01367834

Enrollment

Registered

2011-06-07

Start date

2010-05-31

Completion date

2014-05-31

Last updated

2017-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Turner Syndrome

Keywords

Turner Syndrome, growth hormone, brain development

Brief summary

The purpose of this research study is to learn about brain development in very young girls with Turner syndrome (TS) and the effect that growth hormone (GH) therapy has on early brain development.

Detailed description

Studies in older children and adults have found that IQ (intelligence quotient) in individuals with Turner syndrome (TS) and the general population are similar. However, many individuals with TS have a nonverbal learning disability which may cause problems with imagining and working with objects in space (for example: building blocks, working puzzles, copying designs, driving a car) as well as problems in planning, paying attention, and getting along with people their own age. Studies of brain structure have found changes in the size and function of specific areas of the brain that are involved in these nonverbal processes. However, there are no data published on brain structure or function in girls with Turner Syndrome in the first few years of life when brains are learning and growing most rapidly. In a recent study, very young, short girls with Turner Syndrome (TS)(averaging 2 years in age) were treated with Growth Hormone (GH) and almost reached an average height after 2 years. The risks of GH for the young girls in that study appeared to be the same as those for older girls. Therefore, it is now recommended that GH therapy be considered as soon as a child with TS has growth failure. Growth failure often occurs during infancy; therefore, more children with TS are now receiving GH therapy as young as 12 months of age. In this study, the investigators wish to start understanding what effect GH has on learning and brain growth when given between the ages of 12 and 24 months. In this study, the girls with TS will have developmental studies, a physical examination, magnetic resonance imaging (MRI), and blood drawn at one and two years of age. Some of the girls in this study will receive GH from 12 until 24 months of life, while others will not. Brain growth and development will be compared between those who have been treated with GH and those who have not. This is a pilot study in which the investigators will gather data to design a larger study that can answer these questions.

Interventions

DRUGsomatotropin

Subjects will receive 5 mg somatotropin (growth hormone) pens with cartridges. Subcutaneous injections are to be given every evening around bedtime. Dosing regimen: 50 mcg/kg/day to be adjusted at 4 month intervals to the closest 0.1 mg. Subjects will be given 12 months of treatment (from 12 to 24 months of life). Subjects will visit their pediatrician or pediatric endocrinologist at 4 and 8 months of life.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

11 Months to 13 Months

Healthy volunteers

Inclusion criteria

* Diagnosis of Turner syndrome * Less than the 50th percentile for length for the general female population

Exclusion criteria

* Prior Growth Hormone (GH) therapy * Diabetes * Allergy to metacresol (a preservative in the GH liquid that is injected) * Contraindications for Magnetic Resonance Imaging (MRI) (such as metal in the body) * Part of a Y chromosome in child's karyotype * Parent/guardian is not willing for child to be randomized to be in the treatment group (receives Growth Hormone injections for one year) or the control group (receives no Growth Hormone during the study) * Parent/guardian is not willing for child to have some of her developmental testing digitally recorded for scoring

Design outcomes

Primary

Measure	Time frame	Description
Total Brain Volume	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in total brain volume as determined by magnetic resonance imaging (MRI)

Secondary

Measure	Time frame	Description
White Matter Tracts (SLF)	Change in FA from 12 months of age scan in 24 months of age scan	Change in the fractional anisotropy (FA) of white matter tracts using Diffusion Tensor Imaging (DTI); superior longitudinal fasciculus
Volume of Brain Lobes (Central)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of central brain region (precentral gyrus, postcentral gyrus, rolandic operculum) as determined by MRI.
Volume of Brain Lobes (Frontal)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of frontal lobes as determined by MRI.
Volume of Brain Lobes (Occipital)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of occipital lobes as determined by MRI.
Volume of Brain Lobes (Parietal)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of parietal lobes as determined by MRI.
Volume of Brain Lobes (Limbic)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of parietal lobes as determined by MRI.
Volume of Brain Lobes (Insular Cortex)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of parietal lobes as determined by MRI.
Volume of Brain Lobes (Temporal)	Change in volume from 12 months of age scan in 24 months of age scan	Percent change in volumes of temporal lobes as determined by MRI.

Countries

United States

Participant flow

Recruitment details

Subjects were recruited locally in the UNC\_Chapel Hill pediatric endocrinology clinic and nationally through the Turner Syndrome Society, Turner Syndrome family internet groups, and advertisements on our UNC research website.

Participants by arm

Arm	Count
Growth Hormone Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life. somatotropin: Subjects will receive 5 mg somatotropin (growth hormone) pens with cartridges. Subcutaneous injections are to be given every evening around bedtime. Dosing regimen: 50 mcg/kg/day to be adjusted at 4 month intervals to the closest 0.1 mg. Subjects will be given 12 months of treatment (from 12 to 24 months of life). Subjects will visit their pediatrician or pediatric endocrinologist at 4 and 8 months of life.	11
Control Subjects will receive no GH or placebo.	6
Total	17

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Study was ended.	0	1
Overall Study	Withdrawal by Subject	2	2

Baseline characteristics

Characteristic	Control	Growth Hormone	Total
Age, Categorical <=18 years	6 Participants	11 Participants	17 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	12.73 months STANDARD_DEVIATION 0.5	13.12 months STANDARD_DEVIATION 0.82	12.96 months STANDARD_DEVIATION 0.73
Region of Enrollment United States	6 participants	11 participants	17 participants
Sex: Female, Male Female	6 Participants	11 Participants	17 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 11	0 / 6
serious Total, serious adverse events	0 / 11	0 / 6

Outcome results

Primary