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rhGH Therapy on Hepatic Drug Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00458991
Recruitment Status : Completed
First Posted : April 11, 2007
Last Update Posted : April 27, 2017
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Louisville

Brief Summary:
The purpose of the study is to understand the effect of rhGH therapy on hepatic drug metabolism in children with idiopathic growth hormone deficiency.

Condition or disease Intervention/treatment
Growth Hormone Deficiency, Dwarfism Drug: Dextromethorphan and Caffeine

Detailed Description:
Growth Hormone (GH) deficiency is a prominent cause of short stature, affecting approximately 14,000 children in the US. Although a single study has demonstrated reduces CYP1A2 activity following Gh replacement therapy, the effect of GH on the most abundant phase 1 biotransformation pathways (e.g. CYP2D6 and CYP3A4) remain largely uncharacterized. This information gap exists largely due to the lack of sufficiently safe, specific and non-invasive methods appropriate for the longitudinal evaluation of enzyme activity in young children. We can overcome these problems by employing validated phenotyping methods using caffeine, a commonly ingested dietary substance and dextromethorphan, a safe, non-sedating over the counter anti-tussive agent. Application of these methods will permit us to identify, characterize and describe the isoform-specific effects of rhGH on major phase 1 hepatic drug biotransformation pathways, thereby addressing this information gap with minimal risk to children.

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Study Type : Observational
Actual Enrollment : 9 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Recombinant Human Growth Hormone Therapy and Drug Metabolism
Study Start Date : June 2001
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Intervention Details:
  • Drug: Dextromethorphan and Caffeine
    All subjects received standard medical therapy with rhGH and at specified times low doses of the pharmacologic "probes" (e.g., caffeine and dextromethorphan) as surrogate markers to determine CYP450 activity. The only direct treatment effect measured was the biological response to rhGH.

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 14 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children recently diagnosed with idiopathic GH deficiency who were candidates for rhGH therapy were eligible for enrollment. All subjects were recruited via informed parental consent and patient assent (for children > 7 years). The anticipated sample size was 12 children.

Inclusion Criteria:

  • Children ages 4 to 14 years with a height less than the 5th percentile for age and sex or having a decelerated across two major percentiles (5th, 10th, 25th, 50th, 90th, and 95th) on standard pediatric growth curves, poor growth velocity (less than 5 centimeters/year), radiographic evidence of delayed bone age (i.e. greater than 1 SD below the mean for chronological age) and a documented diagnosis of idiopathic growth hormone deficiency [as determined by failure to raise serum GH concentrations 10 microgram/Liter following provocative testing with two growth hormone secretagogues(e.g. insulin, arginine, or clonidine)].
  • All subjects will be prepubertal, as determined by Tanner staging.

Exclusion Criteria:

  • Children receiving medications known to induce or inhibit hepatic CYP1A2, NAT-2, XO, CYP2D6 or CYP3A4 activity.
  • Subjects with a history of smoking (including exposure to second hand smoke > 8 hours per day) or illicit drug use.
  • Subjects with a history of hepatic, renal, cardiac or thyroid disorders. Presence of hepatic, renal, cardiac or thyroid disease will be established based on clinical history and results of recent laboratory tests conducted as part of the routine medical evaluation of children who are being considered for rhGH therapy.
  • Children experiencing fever or acute viral illness
  • Children who have a history of a hypersensitivity reaction to dextromethorphan or caffeine
  • Children who have received prior treatment with rhGH
  • Children who are receiving corticosteroids or thyroid hormone

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 identifier (NCT number): NCT00458991

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United States, California
University of California at San Diego
San Diego, California, United States, 92103
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Missouri
Children's Mercy Hospital and Clinics
Kansas City, Missouri, United States, 64108
United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-6010
Sponsors and Collaborators
University of Louisville
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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Principal Investigator: Mary J Kennedy, PharmD Virginia Commonwealth University
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Responsible Party: University of Louisville Identifier: NCT00458991    
Other Study ID Numbers: PPRU 10734
U10HD045934-01 ( U.S. NIH Grant/Contract )
First Posted: April 11, 2007    Key Record Dates
Last Update Posted: April 27, 2017
Last Verified: April 2017
Keywords provided by University of Louisville:
Recombinant Human Growth Hormone
growth hormone deficiency
short stature
Additional relevant MeSH terms:
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Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Central Nervous System Stimulants
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents