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

• ClinicalTrials.gov Identifier: NCT00140413
• Recruitment Status: Completed
• First Posted: September 1, 2005
• Results First Posted: April 1, 2015
• Last Update Posted: April 1, 2015
• Sponsor: Children's Hospital Los Angeles
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Mark Borchert, M.D., Children's Hospital Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Growth Hormone Deficiency; Septo-Optic Dysplasia; Hypopituitarism	Drug: Nutropin AQ	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
• Study Start Date: December 2004
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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).

Eligibility Criteria

• Ages Eligible for Study: up to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Childrens Hospital Los Angeles

Los Angeles, California, United States, 90027

Sponsors and Collaborators

Children's Hospital Los Angeles

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

More Information

Additional Information:

Optic Nerve Hypoplasia Research 

• Responsible Party: Mark Borchert, M.D., Pediatric Neuro-Ophthalmologist, Children's Hospital Los Angeles
• ClinicalTrials.gov Identifier: NCT00140413
• Other Study ID Numbers: 03.261
• First Posted: September 1, 2005
• Results First Posted: April 1, 2015
• Last Update Posted: April 1, 2015
• Last Verified: March 2015

Keywords provided by Mark Borchert, M.D., Children's Hospital Los Angeles:

Optic Nerve Hypoplasia

Additional relevant MeSH terms:

Dwarfism, Pituitary; Hypopituitarism; Optic Nerve Hypoplasia; Septo-Optic Dysplasia; Endocrine System Diseases; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Malformations; Eye Diseases, Hereditary; Eye Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Agenesis of Corpus Callosum