304-C03/L3301n: Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency

NCT ID: NCT00362063

Last Updated: 2017-04-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2018-04-30

Brief Summary

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.

Detailed Description

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.

Conditions

Growth Hormone Deficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

growth hormone

children with proven growth hormone deficiency

Group Type: EXPERIMENTAL

growth hormone (Nutropin)

Intervention Type: DRUG

growth hormone (Nutropin), 0.3mg/kg/week administered subcutaneously daily.

healthy controls

No growth hormone is given

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

growth hormone (Nutropin)

growth hormone (Nutropin), 0.3mg/kg/week administered subcutaneously daily.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

The study population will consist of children with newly diagnosed growth hormone deficiency (GHD), between the ages of 1-17 years. The clinical evidence will be provided by one or more of the following criteria: delayed bone age, growth deceleration, short stature (more than 2 SD bellow the mean for the subject's age) and/ or height more than1.5 SD below the predicted mid-parental height. The biochemical diagnosis of GHD will be established by an abnormal growth hormone stimulation test and low IGF-1 and IGFBP-3 (growth factors). The growth hormone stimulation test will be performed following the standard Endocrinology Clinic protocol. The growth hormone stimulation test is considered the "gold standard" to diagnose Growth Hormone Deficiency. This test is part of the standard clinical practice to diagnosed GHD. An abnormal test is defined as a post stimulation Growth Hormone level less than10 ng/mL.

The control group will include healthy children between the ages of 1-17 years, not taking any medication with a normal weight for height and growth factors (IGF-1 and IGFBP-3)."

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Luisa M. Rodriguez

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luisa M Rodriguez

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

H-14859

Identifier Type: -

Identifier Source: org_study_id