Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00194961
Status:
TERMINATED
Last Update Posted:
2008-03-25
First Post:
2005-09-12
Brief Title:
Effect of Growth Hormone on Leptin Cytokines and Body Composition of Children With Growth Failure Due to Chronic Kidney Disease
Sponsor:
Weill Medical College of Cornell University
Organization:
Weill Medical College of Cornell University
Study Overview
Official Title:
A Multicenter Study of the Effect of Recombinant Human Growth Hormone on Leptin and Cytokines in Relation to Body Composition in Pediatric Patients With Growth Failure Due to Chronic Kidney Disease CKD
Status:
TERMINATED
Status Verified Date:
2008-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding was not approved
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Circulating concentrations of cytokines such as leptin tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with chronic kidney disease CKD In light of the increasing recognition that growth hormone receptor signaling involves cytokine pathway activation the investigators hypothesize that maladaptation of cytokine regulation in chronic kidney disease may underlie growth failure Secondly they hypothesize that administration of recombinant human growth hormone rhGH will result in growth rate stimulation in pre-pubertal children with growth impairment due to chronic kidney disease by down regulation of the cytokine pathways
This is a non-randomized open-label study to evaluate the effect of recombinant human growth hormone on biochemicalmetabolic and immunologic parameters in relation to body composition pre- and post-recombinant human growth hormone therapy of pre-pubertal growth hormone naive children The efficacy of recombinant human growth hormone to improve growth velocity in pre-pubertal children with growth failure is a secondary objective Fifteen children are to be studied over a six month period Each patient will serve as hisher own control Six months of growth data prior to study is required
This is a non-randomized open-label study to evaluate the effect of recombinant human growth hormone on biochemicalmetabolic and immunologic parameters in relation to body composition pre- and post-recombinant human growth hormone therapy of pre-pubertal growth hormone naive children The efficacy of recombinant human growth hormone to improve growth velocity in pre-pubertal children with growth failure is a secondary objective Fifteen children are to be studied over a six month period Each patient will serve as hisher own control Six months of growth data prior to study is required
Detailed Description:
Hypothesis The energy cost of growth is increased in experimental CKD Caloric intake has been shown to correlate with height velocity in children with CKD and calorie supplementation has been clearly shown to improve height velocity in children on dialysis However when energy intake exceeds 75 of the recommended allowance further growth improvement does not occur Circulating concentrations of cytokines such as leptin tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD In light of the increasing recognition that growth hormone receptor signaling involves cytokine pathway activation we hypothesize that maladaptation of cytokine regulation in CKD may underlie growth failure Secondly we hypothesize that administration of recombinant human growth hormone rhGH will result in growth rate stimulation in pre-pubertal children with growth impairment due to CKD by down regulation of the cytokine pathways
Specific Aims This investigations primary objective will be to evaluate biochemicalmetabolic and immunologic parameters in relation to body composition pre- and post-rhGH therapy The secondary objective is to examine the efficacy of rhGH to improve growth velocity in prepubertal rhGH naïve children with growth failure secondary to CKD The safety of rhGH will be assessed by measuring the above parameters in addition to identifying if there is an increase in the incidence of slipped capital femoral epiphyses and an increase in progression of the underlying renal disease
Methods of Procedure This is an open-label study to evaluate the efficacy and safety of recombinant human growth hormone in children with chronic kidney disease and growth failure
The study involves obtaining the following
1 Medical History and Physical Examination Subjects will have a complete medical history for any potential conditionsmedications which might affect linear growth growth velocity or responsiveness to rhGH A complete physical examination will be performed including Tanner Staging accurate measurement of standing height or recumbent length if 3 years of age using a stadiometer in triplicate weight in triplicate blood pressure and funduscopic examination at each referring Center Anthropometric measurements will be made at the Body Composition Unit at St Lukes-Roosevelt Medical Center New York NY
2 Routine labs will include a CBC Hgb Hct BUN creatinine liver function studies and albumin
3 Bone Age
4 Leptin
5 Cytokines that will be measured include IL-6 TNF alpha TNFsR Rp55 type1 IL-1beta and IL-1Ra The ratio of IL-1 to IL-1Ra will be measured as intracellular and extracellular IL-1b compared to extracellular IL-Ra measured in circulation and as produced in vitro both spontaneously and in response to activation TNF alpha levels and production both intracellularly and extracellularly will be compared to TNFsRp55 type 1
6 Insulin
7 GH-IGF Axis Proteins
8 Body Composition by DXA
During the two years of the study we anticipate that 15 eligible subjects will receive rhGH at 005 mgkg daily by subcutaneous injection This estimate of patient enrollment is based upon our preliminary data and our experience with the incidence age of onset of CKD and the anticipated change in therapy as some of these patients receive transplants The dose will be calculated based on the initial weight and will be adjusted as needed every three months according to weight A parent or legal guardian will administer all doses at home after appropriate training Following treatment for 6 months and termination from the study patients who remain eligible due to persistent growth retardation will receive daily rhGH as standard of care therapy at their institution and their growth rates will be followed During the course of the study all study subjects will continue medical management and follow-up of their CKD as prescribed by their Pediatric Nephrologist Subjects may require concomitant medications such as erythropoietin calcium supplements sodium bicarbonatesodium citrate phosphate binders calcitriol andor antihypertensives as part on their on-going management
After baseline assessment Time 0 all study subjects will enter a six-month observation phase Medical history physical examination biochemical studies creatinine clearance for glomerular filtration rate GFR HgbHct Glucose Tolerance testing GTT with insulin measurements GH-IGF axis proteins cytokine and leptin studies will be obtained at Time 0 3 months and 6 months At Time 0 and at the end of six months of observation study subjects will also undergo body composition evaluation DXA for a total of two sets of studies Bone age will be assessed at these time points as well Each patient will serve as hisher own control at Time 0 for all these measurements Historical growth data will be obtained back as far as six months and further if possible
Specific Aims This investigations primary objective will be to evaluate biochemicalmetabolic and immunologic parameters in relation to body composition pre- and post-rhGH therapy The secondary objective is to examine the efficacy of rhGH to improve growth velocity in prepubertal rhGH naïve children with growth failure secondary to CKD The safety of rhGH will be assessed by measuring the above parameters in addition to identifying if there is an increase in the incidence of slipped capital femoral epiphyses and an increase in progression of the underlying renal disease
Methods of Procedure This is an open-label study to evaluate the efficacy and safety of recombinant human growth hormone in children with chronic kidney disease and growth failure
The study involves obtaining the following
1 Medical History and Physical Examination Subjects will have a complete medical history for any potential conditionsmedications which might affect linear growth growth velocity or responsiveness to rhGH A complete physical examination will be performed including Tanner Staging accurate measurement of standing height or recumbent length if 3 years of age using a stadiometer in triplicate weight in triplicate blood pressure and funduscopic examination at each referring Center Anthropometric measurements will be made at the Body Composition Unit at St Lukes-Roosevelt Medical Center New York NY
2 Routine labs will include a CBC Hgb Hct BUN creatinine liver function studies and albumin
3 Bone Age
4 Leptin
5 Cytokines that will be measured include IL-6 TNF alpha TNFsR Rp55 type1 IL-1beta and IL-1Ra The ratio of IL-1 to IL-1Ra will be measured as intracellular and extracellular IL-1b compared to extracellular IL-Ra measured in circulation and as produced in vitro both spontaneously and in response to activation TNF alpha levels and production both intracellularly and extracellularly will be compared to TNFsRp55 type 1
6 Insulin
7 GH-IGF Axis Proteins
8 Body Composition by DXA
During the two years of the study we anticipate that 15 eligible subjects will receive rhGH at 005 mgkg daily by subcutaneous injection This estimate of patient enrollment is based upon our preliminary data and our experience with the incidence age of onset of CKD and the anticipated change in therapy as some of these patients receive transplants The dose will be calculated based on the initial weight and will be adjusted as needed every three months according to weight A parent or legal guardian will administer all doses at home after appropriate training Following treatment for 6 months and termination from the study patients who remain eligible due to persistent growth retardation will receive daily rhGH as standard of care therapy at their institution and their growth rates will be followed During the course of the study all study subjects will continue medical management and follow-up of their CKD as prescribed by their Pediatric Nephrologist Subjects may require concomitant medications such as erythropoietin calcium supplements sodium bicarbonatesodium citrate phosphate binders calcitriol andor antihypertensives as part on their on-going management
After baseline assessment Time 0 all study subjects will enter a six-month observation phase Medical history physical examination biochemical studies creatinine clearance for glomerular filtration rate GFR HgbHct Glucose Tolerance testing GTT with insulin measurements GH-IGF axis proteins cytokine and leptin studies will be obtained at Time 0 3 months and 6 months At Time 0 and at the end of six months of observation study subjects will also undergo body composition evaluation DXA for a total of two sets of studies Bone age will be assessed at these time points as well Each patient will serve as hisher own control at Time 0 for all these measurements Historical growth data will be obtained back as far as six months and further if possible
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| M2758s | None | None | None |