Clinical trial NCT00458991: rhGH Therapy on Hepatic Drug Metabolism
Official title: Recombinant Human Growth Hormone Therapy and Drug Metabolism
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Growth Hormone Deficiency, Dwarfism
Keywords: Recombinant Human Growth Hormone
growth hormone deficiency
short stature
phenotyping
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2007-04-11
Enrollment: 9
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Kansas City
country: United States
facility: Children's Mercy Hospital and Clinics
state: Missouri
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital
state: Ohio
Study officials:
affiliation: Virginia Commonwealth University
name: Mary J Kennedy, PharmD
role: PRINCIPAL_INVESTIGATOR
References: