Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency
Recruitment status was Recruiting
The purpose of the proposed study is to investigate the effects of rhGH treatment on glucose, protein and fat metabolism in GHD children. Specifically, the investigators will measure the rates of glucose production, gluconeogenesis, glycogenolysis, insulin sensitivity and glucagon response before and after treatment with rhGH. In addition, the investigators will study changes in protein and fat metabolism pre and post rhGH therapy in children with GHD. The findings in the GHD children will be compared to those of a control group of age and sex matched healthy children.
Hypotheses: H1- The fraction of glucose derived from gluconeogenesis is decreased and that from glycogenolysis is increased in the post-absorptive state in untreated GHD children when compared to healthy children. H2- Treatment with rhGH will not change the overall glucose turnover but will normalize the abnormal partitioning of gluconeogenesis and glycogenolysis in GHD children. H3- GH replacement will reduce urea production and increase estimates of protein synthesis, thus optimizing the availability of amino acids for growth. H4- Untreated children with GHD after an overnight fast will have an increased glucagon challenge response that will decrease after 8 weeks of treatment with rhGH.
Specific Aims: In healthy and newly diagnosed GHD children the investigators will: 1. Measure the Glucose Production Rate (GPR) 2. Determine the fraction of glucose derived from gluconeogenesis and glycogenolysis 3. Estimate insulin sensitivity 4. Measure proteolysis and protein oxidation 5. Determine glucagon challenge response after an overnight fast. The above-mentioned parameters will be re-evaluated in the children with GHD after 8 weeks of rhGH therapy.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency|
- Glucose Production rate,Gluconeogenesis, glycogenolysis. [ Time Frame: 13 hours fasting ] [ Designated as safety issue: Yes ]
- Insulin resistance [ Time Frame: 13 hours fasting ] [ Designated as safety issue: Yes ]
- Proteolysis [ Time Frame: 13 hours fasting ] [ Designated as safety issue: No ]
- Glucagon response [ Time Frame: for 2hrs after glucagon administration ] [ Designated as safety issue: No ]
|Study Start Date:||January 2006|
|Estimated Study Completion Date:||August 2010|
|Estimated Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: growth hormone
children with proven growth hormone deficiency
Drug: growth hormone (Nutropin)
growth hormone (Nutropin), 0.3mg/kg/week administered subcutaneously daily.
No Intervention: healthy controls
No growth hormone is given
Children with growth hormone deficiency (GHD) have increased insulin sensitivity and may present with hypoglycemia during infancy. Treatment with recombinant human growth hormone (rhGH) reduces the risk for hypoglycemia and decreases insulin sensitivity. The investigators hypothesize, that GHD causes a decrease in the fraction of glucose derived form gluconeogenesis and conversely glycogenolysis and insulin sensitivity will be increased, when GHD children are compared to healthy controls. The investigators anticipate that total glucose production will be unaffected by rhGH therapy. Therefore, the GDH subjects treated with rhGH for 8 weeks will have an increase in the fraction of glucose derived form gluconeogenesis and a decrease in that form glycogenolysis and decreased insulin sensitivity. To test this hypothesis, 10 healthy and 10 GHD children will be studied using the stable isotope [U-13C] glucose and Mass Isotopes Distribution Analysis (MIDA). The investigators will be specifically measuring the rate of glucose production, gluconeogenesis, glycogenolysis, insulin sensitivity and glucagon response after an overnight fast. In addition, the investigators will measure changes in protein oxidation, proteolysis and fat metabolism using the stable isotopes [15N2] urea, [1-13C] leucine and concentrations of free fatty acids and b-hydroxybutyrate. The GHD group will be studied at the time of diagnosis and after 8 weeks of rhGH.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00362063
|Contact: Luisa M Rodriguez, MDemail@example.com|
|United States, Texas|
|Baylor College of Medicine||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Lori C Malone, MS 832-822-3784 firstname.lastname@example.org|
|Principal Investigator: Luisa M Rodriguez, MD|
|Principal Investigator:||Luisa M Rodriguez||Baylor College of Medicine|