Long-Term Growth and Skeletal Effects of Early Growth Hormone Treatment in Turner Syndrome

Study Overview
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Brief Summary
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This is an extension study that will gather long-term data on the effect of early growth hormone (GH) treatment on adult height and other aspects of health and development in girls with Turner syndrome. The main purpose is to determine whether girls who received 2 years of GH treatment before 6 years of age achieve taller adult height than girls who were untreated during this time. The study will also look at middle ear and hearing function, and cognitive and behavioral development. Protocol completion is defined as attainment of height velocity less than or equal to 1.0 cm/year, or bone age greater than or equal to 15 years.

Official Title
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Effect of Early Growth Hormone Treatment on Long-term Growth and Skeletal Maturation in Girls With Turner Syndrome

Conditions
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Turner Syndrome

Intervention / Treatment
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* Drug: Humatrope


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously randomized in study B9R-US-GDFG (NCT00406926) Karyotype-proven Turner syndrome Exclusion Criteria: Immediate family members of study site personnel directly affiliated with the study

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 1 Control<br>No drug administration in B9R-US-GDFG (NCT00406926). Humatrope according to investigator's clinical practice and guided by the approved package insert on whether treatment is given. | Drug: Humatrope<br>* According to investigator's clinical practice and guided by the approved package insert<br>* Other names: Growth hormone;|
| Experimental: Experimental 2 Humatrope<br>Humatrope according to investigator's clinical practice and guided by the approved package insert on whether treatment is given. | Drug: Humatrope<br>* According to investigator's clinical practice and guided by the approved package insert<br>* Other names: Growth hormone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Most Mature Height Standard Deviation Score (SDS) | SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Baseline through End of Study (10 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height SDS at Various Ages | SDS reports the number of standard deviations from the mean for age and sex for an individual measurement (normal range is -2 to +2 SDS). Height SDS is derived by subtracting the population mean from individual's height value and then dividing that difference by the population standard deviation. Greater height SDS values indicate greater height. | Age 10, Age 13, Age 16 | 
| Age at Attainment of Tanner 2 Breast Development | The Tanner 2 breast development is the age at first evidence of breast development. | Baseline through End of Study (10 years) | 
| Chronological Age at First Visit Participant Attained Bone Age of 14.5 Years | Bone age was measured by standard radiograph, x-ray at baseline and annually for 10 years or until attainment of height velocity less than or equal to 1.0 centimeter per year (cm/year) and bone age greater or equal to 15 years. | Baseline through End of Study (10 years) | 
| Reports of Serious Adverse Events | Number of serious adverse events (SAEs) reported. Any adverse event from this study that results in one of the following outcomes, or is significant for any other reason were reported as an SAE: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect in the offspring of a study subject, significant for any other reason (includes cancer, other than superficial, and basal cell or squamous cell carcinomas of the skin, that did not meet other serious adverse event criteria). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | Baseline through End of Study (10 years) | 
| Percentage of Participants With Occurrence of Pre-specified Clinically Relevant Events | Percentage of participants for whom certain non-serious, pre-specified adverse events (AEs; those that are commonly observed in Turner syndrome or are known to be related to GH treatment: impaired glucose tolerance, diabetes mellitus, hypothyroidism, benign intracranial hypertension, scoliosis, slipped capital femoral epiphysis, solid tumor/leukemia, pancreatitis, ear infections, and high blood pressure) are reported. | Baseline through End of Study (10 years) | 
| Percentage of Participants With Abnormal Tympanometry Results | Percentage of participants with abnormal tympanometry [defined as middle ear dysfunction / middle ear effusion / patent pressure equalizer tube or possible tympanic membrane perforation] results at baseline, age 10 years, and age 16 years or endpoint. | Baseline, Age 10, Age 16, End of Study (10 years) | 
| Percentage of Participants With Prevalence of Abnormal Audiometry Results | Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. Prevalence was calculated as number of participants with abnormal hearing divided by number of participants with measurable pure tone audiometry results at that visit. | Baseline, Age 10, Age 16, End of Study (10 years) | 
| Percentage of Participants With Abnormal Audiometry Results Based on Pure Tone Average (PTA) | Percentage of participants with abnormal Audiometry results at baseline, age 10 years, and age 16 years or endpoint. PTA is defined as the average of pure tone hearing thresholds at 500, 1000 and 2000 Hz (Hertz), calculated separately for each ear and for each testing method (air or bone); normal PTA is defined as pure tone hearing threshold less than or equal to 20 dB HL (decibels Hearing Level), and abnormal PTA is defined as pure tone hearing threshold greater than 20 DB HL. | Baseline, Age 10, Age 16, End of Study (10 years) |