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

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Mark Borchert, M.D., Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00140413
First received: August 31, 2005
Last updated: March 27, 2015
Last verified: March 2015

August 31, 2005
March 27, 2015
December 2004
February 2014   (final data collection date for primary outcome measure)
Change in Anthropometric Measures Over Time [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
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).
Prevalence and type of endocrinopathies at baseline; growth and obesity at two years.
Complete list of historical versions of study NCT00140413 on ClinicalTrials.gov Archive Site
Not Provided
Endocrine outcomes as correlated with radiographic, ocular, and developmental findings.
Not Provided
Not Provided
 
Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia
Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Growth Hormone Deficiency
  • Septo-Optic Dysplasia
  • Hypopituitarism
Drug: Nutropin AQ
Daily injection. Dosage dependent on weight.
  • 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.
    Intervention: Drug: Nutropin AQ
  • 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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
February 2014
February 2014   (final data collection date for primary outcome measure)

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.
Both
up to 5 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00140413
03.261
No
Mark Borchert, M.D., Children's Hospital Los Angeles
Children's Hospital Los Angeles
Genentech, Inc.
Principal Investigator: Mark Borchert, MD Childrens Hospital Los Angeles; University of Southern California
Principal Investigator: Mitchell Geffner, MD Children's Hospital Los Angeles
Children's Hospital Los Angeles
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP