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

March 27, 2015 updated by: Mark Borchert, M.D., Children's Hospital Los Angeles

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 5 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Group 1: Receiving GH Treatment
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.
Drug: Nutropin AQ
Daily injection. Dosage dependent on weight.
No Intervention: Treatment Group 2: Control
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 normal growth were randomized to treatment or to control. The control group received no intervention; however, control subjects were switched (crossed over) to the GH replacement group if, during the course of the study, they met criteria for growth deceleration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Anthropometric Measures Over Time
Time Frame: 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).
Baseline and 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Los Angeles

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Mark Borchert, MD, Childrens Hospital Los Angeles; University of Southern California
  • Principal Investigator: Mitchell Geffner, MD, Children's Hospital Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

August 31, 2005

First Submitted That Met QC Criteria

August 31, 2005

First Posted (Estimate)

September 1, 2005

Study Record Updates

Last Update Posted (Estimate)

April 1, 2015

Last Update Submitted That Met QC Criteria

March 27, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03.261

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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