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

Primary Purpose

Growth Hormone Deficiency

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
growth hormone (Nutropin)
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Growth Hormone Deficiency focused on measuring growth hormone

Eligibility Criteria

1 Month - 17 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

growth hormone

healthy controls

Arm Description

children with proven growth hormone deficiency

No growth hormone is given

Outcomes

Primary Outcome Measures

Glucose Production rate,Gluconeogenesis, glycogenolysis.

Secondary Outcome Measures

Insulin resistance
Proteolysis
Glucagon response

Full Information

First Posted
August 8, 2006
Last Updated
April 10, 2017
Sponsor
Baylor College of Medicine
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00362063
Brief Title
304-C03/L3301n: Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency
Official Title
Effects of Growth Hormone on Glucose and Protein Metabolism in Children With Growth Hormone Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 2006 (undefined)
Primary Completion Date
April 2018 (Anticipated)
Study Completion Date
April 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
Genentech, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Deficiency
Keywords
growth hormone

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
growth hormone
Arm Type
Experimental
Arm Description
children with proven growth hormone deficiency
Arm Title
healthy controls
Arm Type
No Intervention
Arm Description
No growth hormone is given
Intervention Type
Drug
Intervention Name(s)
growth hormone (Nutropin)
Intervention Description
growth hormone (Nutropin), 0.3mg/kg/week administered subcutaneously daily.
Primary Outcome Measure Information:
Title
Glucose Production rate,Gluconeogenesis, glycogenolysis.
Time Frame
13 hours fasting
Secondary Outcome Measure Information:
Title
Insulin resistance
Time Frame
13 hours fasting
Title
Proteolysis
Time Frame
13 hours fasting
Title
Glucagon response
Time Frame
for 2hrs after glucagon administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)." 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luisa M Rodriguez
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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