Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00134420
Status:
COMPLETED
Last Update Posted:
2016-08-08
First Post:
2005-08-22
Brief Title:
Growth Hormone and Chromosome 18q- and Abnormal Growth
Sponsor:
The University of Texas Health Science Center at San Antonio
Organization:
The University of Texas Health Science Center at San Antonio
Study Overview
Official Title:
Growth Hormone Trial for Children With 18q- and Abnormal Growth
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We the investigators at the University of Texas Health Science Center at San Antonio want to learn if height and IQ intelligence quotient scores are improved by growth hormone GH treatment in children with chromosome 18 deletions and abnormal growth Data from a previous study showed that growth hormone improved height in all children with 18q- and growth hormone deficiency In addition most of the study participants on growth hormone treatment showed an increase in IQ scores
Detailed Description:
HYPOTHESIS
Our hypothesis with reference to children with 18q deletions who have abnormal growth are
growth hormone will improve growth and
growth hormone will improve performance IQ pIQ
Therefore our specific aims are to evaluate the impact of GH treatment on
linear growth in children with 18q deletions who have abnormal growth but who are not classically growth hormone deficient and
pIQ in children with 18q deletions who have abnormal growth
GOALS AND METHODS
We have already investigated the growth axis in 50 individuals with a cytogenetically and molecularly confirmed 18q deletion by determining the height growth velocity insulin-like growth factor 1 IGF1 IGF binding protein 3 IGFBP3 bone maturation and growth hormone GH response to pituitary stimulants clonidine and arginine To summarize children with 18q deletions are short 64 have a height more than 2 SD below the mean Affected children also grow slowly 68 have a growth velocity more than 1 SD below the mean Half of the individuals have delayed bone maturation Growth factors are skewed downward 72 of the IGF1 values and 83 of the IGFBP3 values are below the average for normal children Similarly 72 of the children failed to adequately respond to the GH stimulants In the total group of 50 children 20 40 were classically GH DEFICIENT height -2 SD velocity -1 SD bone age -2 SD IGF1 -1 SD IGFBP3 -1 SD peak GH 10 ngml by polyclonal GH assay and are on GH treatment Of the remaining 30 children 28 have multiple abnormalities of the growth axis primarily growth velocity -1 SD ABNORMAL GROWTH but did not qualify for GH treatment according to criteria set by their private insurer Almost all of these children had abnormalities suggestive of hypothalamic dysfunction involving TSH thyroid stimulating hormone and prolactin None have CNS central nervous system abnormalities of the pituitary on MRI Thus we suspect that many of these children have neurosecretory dysfunction Parental heights are slightly above average father height standard deviation score HTZ 03 - 12 mother HTZ 01 - 11 and none of the children are overweight
Of 8 children with GHD growth hormone deficiency on prolonged GH treatment growth rates are comparable to those reported by the NCGS National Collaborative Growth Study for idiopathic GHD at 1 and 2 years The mean change in height over a 28-month period for the treated group in our study was 18 SD while it was -025 SD in the untreated group p0001 No known complications of GH treatment were encountered Furthermore because of an association between 18q deletion hypomyelination and cognition some non-statural benefits of GH treatment were examined specifically the performance intelligence quotient pIQ was measured using a detailed battery of neuropsychological instruments The pIQ was measured because many of the children are hearing impaired and a full scale IQ which relies on verbal skills would underestimate their abilities The GH-treated group was compared to an untreated group The GH-treated group n8 showed an increase in pIQ of 23 points range 0 to 47 while the untreated group n6 showed no change range -2 to 6p0003 Based on these observations we conclude that GHD children with 18q deletions respond favorably to GH therapy in terms of both linear growth and pIQ In contrast children with 18q deletions with abnormal growth who are not classically GH deficient show little change in height SD and pIQ over time Therefore we propose to study NEW STUDY whether children with 18q deletions with abnormal growth can benefit from GH treatment For purposes of this proposal abnormal growth is defined as a growth velocity -1 SD
Initial auxology endocrine testing and neurocognitive evaluation will be performed at our Center Auxologic and neurocognitive testing will be repeated after 18 months of therapy at our Center These studies are done at our Center to assure consistency of evaluation which is a particular concern for the neurocognitive tests Many of the children will also participate in other studies in our Center MRI imaging psychological evaluations of family function that are not part of this application Children begun on GH treatment will need to be seen by a pediatric endocrinologist for dosage adjustment after 3 6 9 and 12 months The untreated children will also need to be seen by a pediatric endocrinologist for auxologic studies at the same time points We enrolled 20 children in this study Few of the children are located in any single geographic area therefore we will have 12-20 centers seeing individual children Rather than developing new forms standard NCGS intake forms will be used for the intermediate visits by the local pediatric endocrinologists
Control Group We have more than 20 previously studied children 53 - 28 years of age who have abnormal growth and have never received GH All have undergone extensive auxologic hormonal neurocognitive and neuroimaging evaluations These studies were done 154 - 9 months ago range 11-28 months We have already shown that in the absence of intervention height SD and pIQ are stable over time therefore these children can serve as their own controls
We also have 20 children who are GH deficient and on treatment that are participants in another study These children were evaluated prior to the initiation of treatment All are scheduled to be re-evaluated at least twice in a five-year period The data on the first 8 treated children were reported above These children will serve as important disease controls
NAME OF FDA APPROVED DRUG TO BE USED
We are using Nutropin AQ in this study
METHOD OF TREATMENT ASSIGNMENT
All children who have previously been evaluated in our Center were offered the opportunity to receive GH subject to the following limitations
The prior evaluation must have occured at least 12 months preceding the anticipated date of initiation of GH therapy
May not be on GH treatment or have been previously treated with GH
Growth velocity -1 SD with normal weight for lengthheight
Must be willing to return to our Center for reevaluation of auxologic parameters and neurocognitive testing prior to the initiation of GH therapy
Must be willing to administer GH on a daily basis for 12-15 months
Must be willing to return to our Center for re-evaluation after 12-15 months of therapy
The majority of the 20 patients for this study came from the group of children who have been previously evaluated
New children families being seen for their initial visit in our Center will be offered the opportunity to participate in the clinical trial if they have abnormal growth and are not classically GHD However these children will be randomly assigned either to treatment or non-treatment for the initial 12-month period Both treated and untreated children families must comply with limitations 2-6 above
The minority of the 20 patients for this study came from the group of children who are new
TYPE OF RANDOMIZATION
Randomization applied only to children who are new to our Center When the results of growth factor and GH provocative testing are known a two-step process will occur Children who are GHD will be started on GH and entered into an on-going study already underway in our Center They will not qualify for participation in the proposed NEW study Children who have abnormal growth will be assigned to either the treatment or non-treatment category using an adaptive randomization scheme to avoid imbalances in the numbers of subjects allocated to the two groups
PLANNED INTERIM ANALYSIS
GH-treated children will be seen at 3 6 9 and 12 months by their local pediatric endocrinologist for measurement of height and weight review of medical history and dosage adjustment Untreated children will be seen at 3 6 9 and 12 months for measurement of height and weight and review of medical history
Our hypothesis with reference to children with 18q deletions who have abnormal growth are
growth hormone will improve growth and
growth hormone will improve performance IQ pIQ
Therefore our specific aims are to evaluate the impact of GH treatment on
linear growth in children with 18q deletions who have abnormal growth but who are not classically growth hormone deficient and
pIQ in children with 18q deletions who have abnormal growth
GOALS AND METHODS
We have already investigated the growth axis in 50 individuals with a cytogenetically and molecularly confirmed 18q deletion by determining the height growth velocity insulin-like growth factor 1 IGF1 IGF binding protein 3 IGFBP3 bone maturation and growth hormone GH response to pituitary stimulants clonidine and arginine To summarize children with 18q deletions are short 64 have a height more than 2 SD below the mean Affected children also grow slowly 68 have a growth velocity more than 1 SD below the mean Half of the individuals have delayed bone maturation Growth factors are skewed downward 72 of the IGF1 values and 83 of the IGFBP3 values are below the average for normal children Similarly 72 of the children failed to adequately respond to the GH stimulants In the total group of 50 children 20 40 were classically GH DEFICIENT height -2 SD velocity -1 SD bone age -2 SD IGF1 -1 SD IGFBP3 -1 SD peak GH 10 ngml by polyclonal GH assay and are on GH treatment Of the remaining 30 children 28 have multiple abnormalities of the growth axis primarily growth velocity -1 SD ABNORMAL GROWTH but did not qualify for GH treatment according to criteria set by their private insurer Almost all of these children had abnormalities suggestive of hypothalamic dysfunction involving TSH thyroid stimulating hormone and prolactin None have CNS central nervous system abnormalities of the pituitary on MRI Thus we suspect that many of these children have neurosecretory dysfunction Parental heights are slightly above average father height standard deviation score HTZ 03 - 12 mother HTZ 01 - 11 and none of the children are overweight
Of 8 children with GHD growth hormone deficiency on prolonged GH treatment growth rates are comparable to those reported by the NCGS National Collaborative Growth Study for idiopathic GHD at 1 and 2 years The mean change in height over a 28-month period for the treated group in our study was 18 SD while it was -025 SD in the untreated group p0001 No known complications of GH treatment were encountered Furthermore because of an association between 18q deletion hypomyelination and cognition some non-statural benefits of GH treatment were examined specifically the performance intelligence quotient pIQ was measured using a detailed battery of neuropsychological instruments The pIQ was measured because many of the children are hearing impaired and a full scale IQ which relies on verbal skills would underestimate their abilities The GH-treated group was compared to an untreated group The GH-treated group n8 showed an increase in pIQ of 23 points range 0 to 47 while the untreated group n6 showed no change range -2 to 6p0003 Based on these observations we conclude that GHD children with 18q deletions respond favorably to GH therapy in terms of both linear growth and pIQ In contrast children with 18q deletions with abnormal growth who are not classically GH deficient show little change in height SD and pIQ over time Therefore we propose to study NEW STUDY whether children with 18q deletions with abnormal growth can benefit from GH treatment For purposes of this proposal abnormal growth is defined as a growth velocity -1 SD
Initial auxology endocrine testing and neurocognitive evaluation will be performed at our Center Auxologic and neurocognitive testing will be repeated after 18 months of therapy at our Center These studies are done at our Center to assure consistency of evaluation which is a particular concern for the neurocognitive tests Many of the children will also participate in other studies in our Center MRI imaging psychological evaluations of family function that are not part of this application Children begun on GH treatment will need to be seen by a pediatric endocrinologist for dosage adjustment after 3 6 9 and 12 months The untreated children will also need to be seen by a pediatric endocrinologist for auxologic studies at the same time points We enrolled 20 children in this study Few of the children are located in any single geographic area therefore we will have 12-20 centers seeing individual children Rather than developing new forms standard NCGS intake forms will be used for the intermediate visits by the local pediatric endocrinologists
Control Group We have more than 20 previously studied children 53 - 28 years of age who have abnormal growth and have never received GH All have undergone extensive auxologic hormonal neurocognitive and neuroimaging evaluations These studies were done 154 - 9 months ago range 11-28 months We have already shown that in the absence of intervention height SD and pIQ are stable over time therefore these children can serve as their own controls
We also have 20 children who are GH deficient and on treatment that are participants in another study These children were evaluated prior to the initiation of treatment All are scheduled to be re-evaluated at least twice in a five-year period The data on the first 8 treated children were reported above These children will serve as important disease controls
NAME OF FDA APPROVED DRUG TO BE USED
We are using Nutropin AQ in this study
METHOD OF TREATMENT ASSIGNMENT
All children who have previously been evaluated in our Center were offered the opportunity to receive GH subject to the following limitations
The prior evaluation must have occured at least 12 months preceding the anticipated date of initiation of GH therapy
May not be on GH treatment or have been previously treated with GH
Growth velocity -1 SD with normal weight for lengthheight
Must be willing to return to our Center for reevaluation of auxologic parameters and neurocognitive testing prior to the initiation of GH therapy
Must be willing to administer GH on a daily basis for 12-15 months
Must be willing to return to our Center for re-evaluation after 12-15 months of therapy
The majority of the 20 patients for this study came from the group of children who have been previously evaluated
New children families being seen for their initial visit in our Center will be offered the opportunity to participate in the clinical trial if they have abnormal growth and are not classically GHD However these children will be randomly assigned either to treatment or non-treatment for the initial 12-month period Both treated and untreated children families must comply with limitations 2-6 above
The minority of the 20 patients for this study came from the group of children who are new
TYPE OF RANDOMIZATION
Randomization applied only to children who are new to our Center When the results of growth factor and GH provocative testing are known a two-step process will occur Children who are GHD will be started on GH and entered into an on-going study already underway in our Center They will not qualify for participation in the proposed NEW study Children who have abnormal growth will be assigned to either the treatment or non-treatment category using an adaptive randomization scheme to avoid imbalances in the numbers of subjects allocated to the two groups
PLANNED INTERIM ANALYSIS
GH-treated children will be seen at 3 6 9 and 12 months by their local pediatric endocrinologist for measurement of height and weight review of medical history and dosage adjustment Untreated children will be seen at 3 6 9 and 12 months for measurement of height and weight and review of medical history
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None