rhGH Therapy on Hepatic Drug Metabolism
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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 | Intervention |
---|---|
Growth Hormone Deficiency, Dwarfism |
Drug: Dextromethorphan and Caffeine |
Study Type: | Observational |
Study Design: | Observational Model: Cohort Time Perspective: Prospective |
Official Title: | Recombinant Human Growth Hormone Therapy and Drug Metabolism |
Enrollment: | 9 |
Study Start Date: | June 2001 |
Study Completion Date: | September 2008 |
Primary Completion Date: | September 2008 (Final data collection date for primary outcome measure) |
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Drug: Dextromethorphan and Caffeine
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.
Ages Eligible for Study: | 4 Years to 14 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
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
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 |
Principal Investigator: | Mary J Kennedy, PharmD | Virginia Commonwealth University |
Additional Information:
No publications provided
Responsible Party: | Mary Jayne Kennedy, Virginia Commonwealth University |
ClinicalTrials.gov Identifier: | NCT00458991 History of Changes |
Other Study ID Numbers: | PPRU 10734, U10HD045934-01 |
Study First Received: | April 9, 2007 |
Last Updated: | August 4, 2011 |
Health Authority: | United States: Federal Government |
Keywords provided by University of Louisville:
Recombinant Human Growth Hormone growth hormone deficiency short stature phenotyping |
Additional relevant MeSH terms:
Dwarfism Dwarfism, Pituitary Endocrine System Diseases Bone Diseases, Developmental Bone Diseases Musculoskeletal Diseases Genetic Diseases, Inborn Bone Diseases, Endocrine Hypopituitarism Pituitary Diseases Hypothalamic Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Caffeine |
Dextromethorphan Hormones Central Nervous System Stimulants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Neurotransmitter Agents Excitatory Amino Acid Antagonists |
ClinicalTrials.gov processed this record on October 01, 2012