rhGH Therapy on Hepatic Drug Metabolism

Completed

• Conditions: Growth Hormone Deficiency, Dwarfism

• Registration Number: NCT00458991
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2001-06
• Study First Submitted: 2007-04-09
• Study First Submitted QC: 2007-04-10
• Study First Posted: 2007-04-11
• Primary Completion: 2008-09
• Study Completion: 2008-09
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-25
• Last Update Posted: 2017-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Trial Locations

Locations (4)

University of California at San Diego; 🇺🇸 San Diego, California, United States

Children's Mercy Hospital and Clinics; 🇺🇸 Kansas City, Missouri, United States

Rainbow Babies and Children's Hospital; 🇺🇸 Cleveland, Ohio, United States

Kosair Charities Pediatric Clinical Research Unit; 🇺🇸 Louisville, Kentucky, United States