rhGH Therapy on Hepatic Drug Metabolism

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Louisville
ClinicalTrials.gov Identifier:
NCT00458991
First received: April 9, 2007
Last updated: August 4, 2011
Last verified: April 2007
  Purpose

The purpose of the study is to understand the effect of rhGH therapy on hepatic drug metabolism in children with idiopathic growth hormone deficiency.


Condition Intervention
Growth Hormone Deficiency, Dwarfism
Drug: Dextromethorphan and Caffeine

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Recombinant Human Growth Hormone Therapy and Drug Metabolism

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Enrollment: 9
Study Start Date: June 2001
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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

Ages Eligible for Study:   4 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458991

Locations
United States, California
University of California at San Diego
San Diego, California, United States, 92103
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Missouri
Children's Mercy Hospital and Clinics
Kansas City, Missouri, United States, 64108
United States, Ohio
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-6010
Sponsors and Collaborators
University of Louisville
Investigators
Principal Investigator: Mary J Kennedy, PharmD Virginia Commonwealth University
  More Information

Additional Information:
No publications provided

Responsible Party: Mary Jayne Kennedy, Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00458991     History of Changes
Other Study ID Numbers: PPRU 10734, U10HD045934-01
Study First Received: April 9, 2007
Last Updated: August 4, 2011
Health Authority: United States: Federal Government

Keywords provided by University of Louisville:
Recombinant Human Growth Hormone
growth hormone deficiency
short stature
phenotyping

Additional relevant MeSH terms:
Dwarfism
Dwarfism, Pituitary
Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Caffeine
Dextromethorphan
Hormones
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on July 28, 2014