Growth Hormone Deficiency, Hypopituitarism, Septo-Optic Dysplasia
Conditions
Keywords
Optic Nerve Hypoplasia
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.
Interventions
DRUGNutropin AQ
Daily injection. Dosage dependent on weight.
Sponsors
Genentech, Inc.
Children's Hospital Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 5 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from an IRB-approved prospective optic nerve hypoplasia (ONH) registry study at Children's Hospital Los Angeles, between January 2005 through March 2011.
Pre-assignment details
39 participants were screened for eligibility: 20 enrolled in the study; 6 failed to meet inclusion criteria; 9 declined participation; and 4 consented to participate but withdrew from the study prior to beginning any study procedures.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1A: Assigned to GH Subjects with growth deceleration were assigned to the GH replacement treatment group in accordance with standard of care. | 5 |
| Treatment Group 1B: Randomized to GH Subjects with normal growth were randomized to GH treatment or to control (no intervention). | 5 |
| Treatment Group 2: Control Subjects with normal growth were randomized to treatment or to control (no intervention). | 7 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Treatment Group 1A: Assigned to GH | Treatment Group 1B: Randomized to GH | Treatment Group 2: Control | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 5 Participants | 7 Participants | 17 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 28 Months | 41 Months | 26 Months | 30 Months |
| Body Mass Index (BMI) z-score | -0.2 Z-score | 2.06 Z-score | 1.35 Z-score | 1.14 Z-score |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
| Stature z-score | -2.16 Z-score | -0.95 Z-score | -1.3 Z-score | -1.73 Z-score |
| Weight-for-stature z-score | -0.38 Z-score | 1.94 Z-score | 1.34 Z-score | 0.82 Z-score |
| Weight z-score | -1.76 Z-score | 0.6 Z-score | -1.36 Z-score | -1.36 Z-score |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 13 | 0 / 3 |
| serious Total, serious adverse events | 0 / 13 | 0 / 3 |
Outcome results
Primary
Change in Anthropometric Measures Over Time
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).
Time frame: Baseline and 36 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment Group 1: Receiving Growth Hormone Treatment | Change in Anthropometric Measures Over Time | Change in stature z-score | 1.97 Z-score |
| Treatment Group 1: Receiving Growth Hormone Treatment | Change in Anthropometric Measures Over Time | Change in weight z-score | 1.22 Z-score |
| Treatment Group 1: Receiving Growth Hormone Treatment | Change in Anthropometric Measures Over Time | Change in weight-for-stature z-score | 0.52 Z-score |
| Treatment Group 1: Receiving Growth Hormone Treatment | Change in Anthropometric Measures Over Time | Change in body mass index (BMI) z-score | -0.06 Z-score |
| Treatment Group 2: Control | Change in Anthropometric Measures Over Time | Change in body mass index (BMI) z-score | -0.505 Z-score |
| Treatment Group 2: Control | Change in Anthropometric Measures Over Time | Change in stature z-score | -0.61 Z-score |
| Treatment Group 2: Control | Change in Anthropometric Measures Over Time | Change in weight-for-stature z-score | -0.37 Z-score |
| Treatment Group 2: Control | Change in Anthropometric Measures Over Time | Change in weight z-score | -0.38 Z-score |
| Treatment Group 3: Control Crossed Over to Treatment | Change in Anthropometric Measures Over Time | Change in body mass index (BMI) z-score | -1.035 Z-score |
| Treatment Group 3: Control Crossed Over to Treatment | Change in Anthropometric Measures Over Time | Change in weight z-score | 0.58 Z-score |
| Treatment Group 3: Control Crossed Over to Treatment | Change in Anthropometric Measures Over Time | Change in weight-for-stature z-score | 0.95 Z-score |
| Treatment Group 3: Control Crossed Over to Treatment | Change in Anthropometric Measures Over Time | Change in stature z-score | 1.39 Z-score |