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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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Hypotheses:
Aims:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Group 1: Receiving GH Treatment | Experimental | 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. |
|
| Treatment Group 2: Control | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nutropin AQ | Drug | Daily injection. Dosage dependent on weight. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline and 36 months |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Borchert, MD | Childrens Hospital Los Angeles; University of Southern California | Principal Investigator |
| Mitchell Geffner, MD | Children's Hospital Los Angeles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Hospital Los Angeles | Los Angeles | California | 90027 | United States |
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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Group 1: Receiving Growth Hormone 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 replacement treatment group in accordance with standard of care. Subjects with normal growth were randomized to treatment or to control (no intervention). The starting dose for GH replacement was calculated as 0.3 mg/kg/wk and subsequently modified based on observed length/height velocity and serum IGF-I levels. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Please note, 3 children were unenrolled from the study and were therefore excluded from our analysis of results. Therefore, while the participant flow section lists 20 participants, the baseline analysis and results are based on 17 participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment Group 1A: Assigned to GH | Subjects with growth deceleration were assigned to the GH replacement treatment group in accordance with standard of care. |
| BG001 | Treatment Group 1B: Randomized to GH |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Posted | Median | Inter-Quartile Range | Z-score | Baseline and 36 months |
|
36 months (study duration)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Group 1: Receiving Growth Hormone Treatment | The denominator below (# at risk) is based on the number of subjects in Group 1 who received at least one dose of growth hormone. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Non-systematic Assessment | The event was expected, consistent with the investigator's brochure and reported as a possible risk in the informed consent form. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mark Borchert | Children's Hospital Los Angeles | 323-361-6219 | mborchert@chla.usc.edu |
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| ID | Term |
|---|---|
| D004393 | Dwarfism, Pituitary |
| D025962 | Septo-Optic Dysplasia |
| D007018 | Hypopituitarism |
| D000080344 | Optic Nerve Hypoplasia |
| ID | Term |
|---|---|
| D004392 | Dwarfism |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| ID | Term |
|---|---|
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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Subjects with normal growth were randomized to GH treatment or to control (no intervention).
| BG002 | Treatment Group 2: Control | Subjects with normal growth were randomized to treatment or to control (no intervention). |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | Months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Weight z-score | 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). | Median | Inter-Quartile Range | Z-score |
|
| Stature z-score | 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). | Median | Inter-Quartile Range | Z-score |
|
| Weight-for-stature z-score | Weight (wt.) for stature expresses wt. relative to stature (length or height); data are not age specific. The wt. for stature reference data from CDC growth charts compares a child's wt. with the wt. distribution of children of the same stature but not necessarily of the same age. 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. All z-scores were obtained using Epi Info ™ 3.5.4. (Centers for Disease Control, Atlanta, GA). | Median | Inter-Quartile Range | Z-score |
|
| Body Mass Index (BMI) z-score | BMI adjusts weight for stature and is calculated as weight (kg)/height (m) squared. In children, BMI is age specific. BMI reference data from the CDC growth charts compares a child's BMI with the BMI distribution of children of the same age but not necessarily of the same stature. 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. All z-scores were obtained using Epi Info ™ 3.5.4. (Centers for Disease Control, Atlanta, GA). | Median | Inter-Quartile Range | Z-score |
|
| OG001 | 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. A total of 7 subjects were randomized to the control group, 3 of whom were crossed over to treatment due to growth deceleration. Outcome measures for these 3 who crossed over were analyzed separately, under Treatment Group 3. |
| OG002 | Treatment Group 3: Control Crossed Over to Treatment | 3 control subjects were switched (crossed over) to the GH replacement group during the course of the study due to growth deceleration. |
|
|
| 0 |
| 13 |
| 1 |
| 13 |
| EG001 | Treatment Group 2: Control | The denominator below (# at risk) is based on the number of subjects in Group 2 who received at least one dose of growth hormone. Per protocol, control subjects received no intervention; however, 3 control subjects were switched (crossed over) to the GH replacement group during the course of the study due to growth deceleration. | 0 | 3 | 0 | 3 |
|
With respect to any proposed publication, the PI must submit to the sponsor a copy of the proposed publication at least 2 months prior to submission for the purposes of: providing the sponsor the oppotunity to review and comment on the contents of proposed publication; and to identify any trade secret, proprietary or confidential information to be removed from the proposed publication. The sponsor will provide comments within 30 days of receipt of proposed publication.
| D001849 |
| Bone Diseases, Endocrine |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D000093922 | Congenital Cranial Dysinnervation Disorders |
| D015840 | Oculomotor Nerve Diseases |
| D015835 | Ocular Motility Disorders |
| D003389 | Cranial Nerve Diseases |
| D061085 | Agenesis of Corpus Callosum |
| D009421 | Nervous System Malformations |
| D005128 | Eye Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009901 | Optic Nerve Diseases |
| D015785 | Eye Diseases, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |