Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2010 by Baylor College of Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Genentech
Information provided by:
Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00362063
First received: August 8, 2006
Last updated: December 21, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention
Growth Hormone Deficiency
Drug: growth hormone (Nutropin)

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Glucose Production rate,Gluconeogenesis, glycogenolysis. [ Time Frame: 13 hours fasting ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   1 Month to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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)."

Exclusion Criteria:

The exclusion criteria will include for both groups age less than 1 or more than 17 y/o, evidence of anemia (hemoglobin less tan 12 mg/dl), the use of medications that can directly impact blood sugar (steroids, oral contraceptives etc), history or proof of chemical abuse, lack of supportive family environment, allergies to local anesthetics and elevated liver enzymes. The GHD children will have a head MRI, and children with evidence of tumors or space occupying lesions will be excluded. GHD subjects with adrenal insufficiency and or hypothyroidism. will not be considered for the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00362063

Contacts
Contact: Luisa M Rodriguez, MD 832-822-1002 lrodrigu@bcm.tmc.edu

Locations
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Lori C Malone, MS    832-822-3784    lmalone@bcm.tmc.edu   
Principal Investigator: Luisa M Rodriguez, MD         
Sponsors and Collaborators
Baylor College of Medicine
Genentech
Investigators
Principal Investigator: Luisa M Rodriguez Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Luisa M. Rodriguez, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00362063     History of Changes
Other Study ID Numbers: 304-C03/L3301n
Study First Received: August 8, 2006
Last Updated: December 21, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
growth hormone

Additional relevant MeSH terms:
Dwarfism, Pituitary
Dwarfism
Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014