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

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ClinicalTrials.gov Identifier: NCT00362063
Recruitment Status : Active, not recruiting
First Posted : August 9, 2006
Last Update Posted : April 12, 2017
Genentech, Inc.
Information provided by (Responsible Party):
Luisa M. Rodriguez, Baylor College of Medicine

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.

Condition or disease Intervention/treatment
Growth Hormone Deficiency Drug: growth hormone (Nutropin)

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency
Study Start Date : January 2006
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Glucose Production rate,Gluconeogenesis, glycogenolysis. [ Time Frame: 13 hours fasting ]

Secondary Outcome Measures :
  1. Insulin resistance [ Time Frame: 13 hours fasting ]
  2. Proteolysis [ Time Frame: 13 hours fasting ]
  3. Glucagon response [ Time Frame: for 2hrs after glucagon administration ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00362063

United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Genentech, Inc.
Principal Investigator: Luisa M Rodriguez Baylor College of Medicine

Responsible Party: Luisa M. Rodriguez, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00362063     History of Changes
Other Study ID Numbers: H-14859
First Posted: August 9, 2006    Key Record Dates
Last Update Posted: April 12, 2017
Last Verified: April 2017

Keywords provided by Luisa M. Rodriguez, Baylor College of Medicine:
growth hormone

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