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

• Sponsor: Rebecca Knickmeyer Santelli, PhD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01367834
• Collaborator: Pfizer (Industry)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Turner Syndrome	Drug: somatotropin	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Growth Hormone on Early Brain Development in Girls With Turner Syndrome
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 11 Months to 13 Months
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• Rebecca Knickmeyer Santelli, PhD
• Pfizer

Investigators

• Principal Investigator: Rebecca Knickmeyer, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rebecca Knickmeyer Santelli, PhD, Associate Professor, University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT01367834
• Other Study ID Numbers: 09-2171
• First Posted: Jun 7, 2011
• Last Update Posted: Mar 24, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Rebecca Knickmeyer Santelli, PhD, Associate Professor, University of North Carolina, Chapel Hill: Turner Syndrome; growth hormone; brain development
• Additional relevant MeSH terms: Turner Syndrome; Gonadal Dysgenesis; Syndrome; Hormones

Study Results

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.

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	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.	Subjects will receive no GH or placebo.
Period Title: Overall Study
STARTED	11	6
COMPLETED	9	3
NOT COMPLETED	2	3

Baseline Characteristics

Arm/Group Title	Growth Hormone	Control	Total
Arm/Group Description	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.	Subjects will receive no GH or placebo.	Total of all reporting groups
Overall Participants	11	6	17
Age (Count of Participants)
<=18 years	11 100%	6 100%	17 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	13.12 (0.82)	12.73 (0.50)	12.96 (0.73)
Sex: Female, Male (Count of Participants)
Female	11 100%	6 100%	17 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	6 100%	17 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	18.22 (1.99)	19.78 (NA)

2. Secondary Outcome

Title	Volume of Brain Lobes (Occipital)
Description	Percent change in volumes of occipital lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	14.83 (2.21)	12.16 (NA)

3. Secondary Outcome

Title	White Matter Tracts (SLF)
Description	Change in the fractional anisotropy (FA) of white matter tracts using Diffusion Tensor Imaging (DTI); superior longitudinal fasciculus
Time Frame	Change in FA from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	4	1
Mean (Standard Deviation) [percentage change]	15.12 (5.01)	16.35 (NA)

4. Secondary Outcome

Title	Volume of Brain Lobes (Central)
Description	Percent change in volumes of central brain region (precentral gyrus, postcentral gyrus, rolandic operculum) as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	17.63 (2.13)	10.23 (NA)

5. Secondary Outcome

Title	Volume of Brain Lobes (Frontal)
Description	Percent change in volumes of frontal lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	15.43 (1.84)	14.38 (NA)

6. Secondary Outcome

Title	Volume of Brain Lobes (Temporal)
Description	Percent change in volumes of temporal lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	10.79 (3.68)	5.08 (NA)

7. Secondary Outcome

Title	Volume of Brain Lobes (Parietal)
Description	Percent change in volumes of parietal lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	18.86 (5.01)	11.95 (NA)

8. Secondary Outcome

Title	Volume of Brain Lobes (Limbic)
Description	Percent change in volumes of parietal lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	15.43 (2.99)	22.71 (NA)

9. Secondary Outcome

Title	Volume of Brain Lobes (Insular Cortex)
Description	Percent change in volumes of parietal lobes as determined by MRI.
Time Frame	Change in volume from 12 months of age scan in 24 months of age scan

Outcome Measure Data

Analysis Population Description

Note that only subjects with usable MRI data are included in this analysis (this is a subset of all children completing the protocol).

Arm/Group Title	Growth Hormone	Control
Arm/Group Description	Subjects in the growth hormone (GH) arm will receive GH injections from 12-24 months of life.	No intervention
Measure Participants	5	1
Mean (Standard Deviation) [percentage change]	15.79 (2.11)	19.78 (NA)

Adverse Events

Time Frame	Baseline and 1 year
Arm/Group Title	Growth Hormone		Control
Arm/Group Description	Subjects in the somatotropin (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.		Subjects will receive no GH or placebo.
All Cause Mortality
	Growth Hormone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Growth Hormone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Growth Hormone		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/6 (0%)

Limitations/Caveats

Low scan success rate and subject drop out resulted in small sample size (5 GH treated, 1 control).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.