Brief Title
rhGH Therapy on Hepatic Drug Metabolism
Official Title
Recombinant Human Growth Hormone Therapy and Drug Metabolism
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.
Study Type
Observational
Condition
Growth Hormone Deficiency, Dwarfism
Intervention
Dextromethorphan and Caffeine
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
9
Start Date
June 2001
Completion Date
September 2008
Primary Completion Date
September 2008
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
Gender
All
Ages
4 Years - 14 Years
Accepts Healthy Volunteers
No
Contacts
Mary J Kennedy, PharmD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00458991
Organization ID
PPRU 10734
Secondary IDs
U10HD045934-01
Responsible Party
Sponsor
Study Sponsor
University of Louisville
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study Sponsor
Mary J Kennedy, PharmD, Principal Investigator, Virginia Commonwealth University
Verification Date
April 2017