Clinical trial NCT00783783: CYP2D6 Pharmacogenetics in Risperidone-Treated Children
Official title: CYP2D6 PHARMACOGENETICS IN RISPERIDONE-TREATED CHILDREN AND ADOLESCENTS WITH PSYCHIATRIC OR NEURODEVELOPMENTAL DISORDERS
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Psychiatric Disorders
Neurodevelopmental Disorders
Keywords: Psychiatric disorders
Neurodevelopmental disorders
Autism
Risperidone
Pharmacogenetics
Pharmacokinetics
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Ohio State University
name: Rainbow Babies and Children's Hospital
First posted: 2008-11-02
Enrollment: 47
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will include up to 41 risperidone-treated children and adolescents with psychiatric or neurodevelopmental (ND) disorders who participated in one of two previous risperidone pharmacokinetics investigations.

To have a larger sample of poor metabolizer subjects, we plan to enroll at least 8 additional subjects who are on stable treatment with risperidone, and perform risperidone pharmacokinetics analyses. Prospectively enrolled subjects (n = 8) will be CYP2D6 poor metabolizers and will include White / Caucasian subjects, of any socioeconomic status, and will be recruited from inpatients or outpatients at Cincinnati Children's Hospital

Brief summary: Risperidone is an important medication used to treat children with psychiatric illnesses or neurodevelopmental disorders, such as autism. Despite excellent symptom control, the potential for side effects is worrisome. Treating these disorders is difficult because not everyone responds the same way to the same risperidone dose. One reason for this is genetic differences in how people break down the drug. Understanding these differences will help clinicians choose a dose and better predict the response so patients will be treated successfully with a lower risk for side effects. This study will research these genetic differences in children with psychiatric or neurodevelopmental disorders. Hypothesis: The inter-patient variability in risperidone pharmacokinetics and exposure, adverse events, and clinical response in patients with psychiatric or neurodevelopmental disorders is associated with identifiable pharmacogenetic factors, such as CYP2D6 single nucleotide polymorphisms (SNPs).


Eligibility criteria: Inclusion Criteria:

* Previous risperidone PK study participation (CCHMC, Rainbow Babies and Children's Hospital or OSU)
* CYP2D6 PM predicted phenotype
* Actively taking risperidone
* Under 18 years of age at time of enrollment
* Signed, dated informed consent forms

Exclusion Criteria:

* Investigators are unable to contact the subject/legal guardian(s)
* Subject is no longer taking risperidone
* CYP2D6 predicted phenotype other than PM
* Subject is non-White, with respect to race, for PK study participation
* Subject is 18 years of age or older
* Subject is less than 5 years of age
* Subject is pregnant at the time of the full PK study
* Subject/legal guardian unwilling or unable to participate in the study

Primary outcomes:
measure: association of common CYP2D6 polymorphisms with risperidone area under the curve
timeFrame: pre-dose (sample 1 = 0-30 minutes before first oral dose), and three at well-timed post-dose points (sample 2 = 15-30 minutes after dose; sample 3 = 60-90 minutes after dose; sample 4 = 4-6 hours after dose)
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Shannon N Saldana, PharmD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aman MG, Vinks AA, Remmerie B, Mannaert E, Ramadan Y, Masty J, Lindsay RL, Malone K. Plasma pharmacokinetic characteristics of risperidone and their relationship to saliva concentrations in children with psychiatric or neurodevelopmental disorders. Clin Ther. 2007 Jul;29(7):1476-86. doi: 10.1016/j.clinthera.2007.07.026.
citation: Cabovska B, Cox SL, Vinks AA. Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 1;852(1-2):497-504. doi: 10.1016/j.jchromb.2007.02.007. Epub 2007 Feb 15.
citation: Sherwin CM, Saldana SN, Bies RR, Aman MG, Vinks AA. Population pharmacokinetic modeling of risperidone and 9-hydroxyrisperidone to estimate CYP2D6 subpopulations in children and adolescents. Ther Drug Monit. 2012 Oct;34(5):535-44. doi: 10.1097/FTD.0b013e318261c240.