rhGH Therapy on Hepatic Drug Metabolism

NCT ID: NCT00458991

Last Updated: 2017-04-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 9 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2001-06-30
• Study Completion Date: 2008-09-30

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.

Conditions

Growth Hormone Deficiency, Dwarfism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary J Kennedy, PharmD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

University of California at San Diego

San Diego, California, United States

Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, United States

Children's Mercy Hospital and Clinics

Kansas City, Missouri, United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

U10HD045934-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PPRU 10734

Identifier Type: -

Identifier Source: org_study_id