rhGH Therapy on Hepatic Drug Metabolism

Growth Hormone Deficiency, Dwarfism Clinical Trial

Official title:

Recombinant Human Growth Hormone Therapy and Drug Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00458991
• Other study ID #: PPRU 10734
• Secondary ID: U10HD045934-01
• Status: Completed
• Phase: N/A
• First received: April 9, 2007
• Last updated: April 25, 2017
• Start date: June 2001
• Est. completion date: September 2008

Study information

• Verified date: April 2017
• Source: University of Louisville
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 14 Years

Eligibility

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

Related Conditions & MeSH terms

• Dwarfism
• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency, Dwarfism

Intervention

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.

Locations

Country	Name	City	State
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Children's Mercy Hospital and Clinics	Kansas City	Missouri
United States	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	University of California at San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Louisville	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

External Links

•   Pediatric Pharmacology Research Unit Website