NCT01118858

Exogenous and Endogenous Biomarkers of CYP2D6 and CYP3A4 Variability in Pediatrics

Completed Last updated 19 July 2017

What this trial tests

trial in Drug Metabolism Phenotype in 205 participants. Completed in 1 October 2015.

Timeline

1 April 2010

Primary endpoint
1 October 2015

1 October 2015

Quick facts

Lead sponsor	Children's Mercy Hospital Kansas City
Status	Completed
Study type	OBSERVATIONAL
Enrollment	205
Start date	1 April 2010
Primary completion	1 October 2015
Estimated completion	1 October 2015
Sites	2 locations across United States

Conditions studied

• Drug Metabolism Phenotype — all drugs for Drug Metabolism Phenotype →

Sponsor

Children's Mercy Hospital Kansas City

Who can join

Adults 7 to 15, any sex, with Drug Metabolism Phenotype. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Characterize the change in CYP2D6 and CYP3A4 phenotype through adolescence
  Time frame: Three years
  Growth and development adds an additional level of complexity as the genotype-phenotype relationship may change as children grow and develop. The purpose of this proposal is to characterize the relative roles of ontogeny and genetic variation towards changes in CYP2D6 and CYP3A4 activity during adolescence. Because some drugs commonly used to treat ADHD are metabolized by CYP2D6 and CYP3A4, the in

Sponsor's own description

Cytochrome P450 2D6 (CYP2D6) is an important enzyme in the body for breaking down many medications that are commonly used in children of various ages. The purpose of this proposal is to investigate the relative roles of development and genetic variation in CYP2D6 activity in school-aged children and adolescents with attention deficit and hyperactivity disorder and health controls using the over-the-counter cough suppressant, dextromethorphan or "DM", a standard probe for determining CYP2D6 phenotype. Embedded in the study design are sub-studies to search for by-products of normal body metabolism that reflect differences in enzyme activity, and a pharmacokinetic study to assess the consequences of CYP2D6 genetic variation on the systemic exposure to medications used by this patient population. Ultimately, the goal of the research is to personalize the use of medications in children by selecting the appropriate dose of the correct medication for individual patients.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Common CYP2D6 polymorphisms affecting alternative splicing and transcription: long-range haplotypes with two regulatory variants modulate CYP2D6 activity.
   Wang D, Poi MJ, Sun X, Gaedigk A, et al · · 2014 · cited 90× · PMID 23985325 · DOI 10.1093/hmg/ddt417
2. Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children.
   McWilliam SJ, Antoine DJ, Sabbisetti V, Pearce RE, et al · · 2014 · cited 54× · PMID 24661102 · DOI 10.2217/bmm.14.36
3. A longitudinal study of cytochrome P450 2D6 (CYP2D6) activity during adolescence.
   Leeder JS, Gaedigk A, Wright KJ, Staggs VS, et al · · 2022 · cited 4× · PMID 35997001 · DOI 10.1111/cts.13380