Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia

Phase 4

Completed

• Conditions: Growth Hormone Deficiency; Hypopituitarism; Septo-Optic Dysplasia
• Interventions: Drug: Nutropin AQ

• Registration Number: NCT00140413
• Lead Sponsor: Children's Hospital Los Angeles

Brief Summary

Hypotheses:

1. The prevalence of endocrinopathies, and growth hormone (GH) deficiency in particular, among young children diagnosed with optic nerve hypoplasia (ONH) is higher than is commonly thought.

2. Early treatment of children with ONH and GH-deficiency can prevent adverse outcomes.

Aims:

1. Determine the prevalence and types of endocrinopathies in children diagnosed with ONH.

2. Correlate endocrine outcome with radiographic, ocular, and developmental findings in children with ONH.

3. Examine the effect of GH treatment on growth and obesity in children with ONH, GH-deficiency, and either subnormal or normal growth compared to children with ONH that are not GH-deficient.

4. Compare growth outcomes between children with isolated GH-deficiency and those with multiple hormone deficiencies.

Detailed Description

Subjects for this study will be recruited from active and newly enrolled subjects in our larger ONH study. The study duration is three years and we anticipate 38 subjects will enroll. Subjects will be recruited for this study if they present with either growth deceleration or at least one subnormal result for IGF-1 or IGFBP-3.

Baseline information collected includes: height, weight, head circumference, examinations by an endocrinologist and ophthalmologist, endocrine laboratory testing, fundus photography, electrophysiology testing, head MRI, and a developmental assessment. A glucagon stimulation test will be performed and subjects who are deemed GH-deficient and who have delayed growth will be assigned to GH treatment, in line with standard clinical practice. Those with normal growth but determined to be GH-deficient by a glucagon stimulation test will be randomized to treatment with GH vs control (no intervention; observation only).

Subjects assigned or randomized to treatment with GH will be provided with GH for the duration of their participation in the study. Enrolled subjects will return every four months to monitor progress. Subjects will undergo a physical examination at each visit, including height, weight, head circumference, and body fat. In addition, subjects assigned or randomized to growth hormone will have laboratory testing of thyroid, IGF-1 and IGFBP-3 hormones, and fasting lipid levels.

Study Timeline

• Study Start: 2004-12
• Study First Submitted: 2005-08-31
• Study First Submitted QC: 2005-08-31
• Study First Posted: 2005-09-01
• Primary Completion: 2014-02
• Study Completion: 2014-02
• Results First Submitted: 2015-02-17
• Status Verified: 2015-03
• Results First Submitted QC: 2015-03-27
• Last Update Submitted: 2015-03-27
• Results First Posted: 2015-04-01
• Last Update Posted: 2015-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• New subjects diagnosed with ONH less than or equal to 2 years of age and subjects actively enrolled (in currently approved prospective ONH study) will be eligible for enrollment.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group 1: Receiving GH Treatment	Nutropin AQ	Treatment group assignment was based on subject's stature SDS relative to the mid-parental target height (MPTH) at baseline and subsequent classification as growth deceleration or normal growth. Subjects with growth deceleration were assigned to the GH treatment group in accordance with standard of care. Subjects with normal growth were randomized to treatment or to control (no intervention). The intervention was Nutropin AQ. The starting dose was calculated as 0.3 mg/kg/wk and subsequently modified based on observed length/height velocity and serum IGF-I levels.

Primary Outcome Measures

Name	Time	Method
Change in Anthropometric Measures Over Time	Baseline and 36 months	Primary outcome measures included change in stature, weight, BMI, and weight-for-stature z-scores over the course of the study. Z-score indicates how many standard deviations an element is from the mean. It is calculated as z = (x - µ) σ, where µ is the mean of the population, and σ is the standard deviation of the population. A positive z-score indicates a datum above the mean, while a negative z-score indicates a datum below the mean. All z-scores were obtained using Epi Info ™ 3.5.4. (Centers for Disease Control, Atlanta, GA).

Trial Locations

Locations (1)

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States