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

NCT ID: NCT00140413

Last Updated: 2015-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2014-02-28

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.

Conditions

Growth Hormone Deficiency; Septo-Optic Dysplasia; Hypopituitarism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nutropin AQ

Intervention Type: DRUG

Daily injection. Dosage dependent on weight.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Nutropin AQ

Daily injection. Dosage dependent on weight.

Intervention Type: DRUG

Eligibility Criteria

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.

• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Children's Hospital Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Mark Borchert, M.D.

Pediatric Neuro-Ophthalmologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mark Borchert, MD

Role: PRINCIPAL_INVESTIGATOR

Childrens Hospital Los Angeles; University of Southern California

Mitchell Geffner, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

Locations

Childrens Hospital Los Angeles

Los Angeles, California, United States

Countries

United States

Other Identifiers

03.261

Identifier Type: -

Identifier Source: org_study_id