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

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.

Study Overview

• Status: Completed
• Conditions: Turner Syndrome
• Intervention / Treatment: Drug: somatotropin

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 months to 1 year (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Growth Hormone; Subjects in the somatotropin (growth hormone, GH) arm will receive GH injections from 12-24 months of life.	Drug: 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.; Other Names: Genotropin; Growth hormone
NO_INTERVENTION: Control; Subjects will receive no GH or placebo.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rebecca Knickmeyer Santelli, PhD
• Collaborators: Pfizer
• Investigators: Principal Investigator: Rebecca Knickmeyer, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: June 2, 2011
• First Submitted That Met QC Criteria: June 6, 2011
• First Posted (ESTIMATE): June 7, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 24, 2017
• Last Update Submitted That Met QC Criteria: February 3, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: growth hormone; Turner Syndrome; brain development
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Syndrome; Turner Syndrome; Gonadal Dysgenesis; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 09-2171

Plan for Individual participant data (IPD)

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