Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism

Tracking Information
First Submitted Date ICMJE	November 6, 2006
First Posted Date ICMJE	November 8, 2006
Last Update Posted Date	February 6, 2008
Study Start Date ICMJE	December 2006
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 7, 2006)	Dynamic pupillometry; Pharmacokinetics; AUC
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00397059 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 7, 2006)	Cmax; Tmax; T½
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism
Official Title ICMJE	Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism
Brief Summary	To study the impact of CYP2C19 polymorphism on escitalopram pharmacokinetics and pharmacodynamics measured as changes in pupil diameter
Detailed Description	Escitalopram, the therapeutic active S-enantiomer of citalopram, is a selective serotonine reuptake inhibitor (SSRI) used for treatment of depression and anxiety disorders. The antidepressant effect is probably due to a stimulation of the serotonergic neurotransmission caused by the inhibition of the presynaptic serotonin reuptake. This inhibition may also be responsible for the increased pupil diameter seen in volunteers treated with racemic citalopram. Based on escitaloprams pharmacodynamic properties it is expected to have the same affect on pupil diameter. A dose/response relationship has not yet been established but theoretically the pupillary changes might serve as a biomarker for the serotonergic effect of escitalopram. Escitalopram is demethylated in part by the polymorphic cytochrome P450 enzyme 2C19 (CYP2C19); but the impact of CYP2C19 polymorphism on the total metabolism of escitalopram is still to be investigated. Objective: The aim of this study is to investigate the pharmacokinetics and pharmacodynamics in CYP2C19 extensive metabolizers (EMs) and poor metabolizers (PMs) and to investigate whether change in pupil size reaction to a light stimulus can act as a biomarker for the serotonergic effect of escitalopram. The study will be conducted as a randomized, double blinded; placebo controlled two phases cross-over trial with single and repeated doses of 20 mg escitalopram and equivalent placebo. Sixteen healthy volunteers (8 EMs and 8 PMs) will participate in the trial. Prior to the trial, approximately 400 volunteers will be phenotyped by omeprazole metabolic ratio in order to identify the CYP2C19 EMs and PMs. During the two phases blood samples will be drawn and pupil sizes will be measured at fixed time points after drug administration.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double; Primary Purpose: Treatment
Condition ICMJE	Healthy
Intervention ICMJE	Drug: Escitalopram
Study Arms	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: November 7, 2006)	16
Original Enrollment ICMJE	Same as current
Actual Study Completion Date	October 2007
Actual Primary Completion Date	October 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Healthy volunteer; Age: 18-45 years; Phenotyped for CYP2C19 activity Exclusion Criteria: Drug or alcohol abuse; Allergy towards escitalopram
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 45 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Denmark
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00397059
Other Study ID Numbers ICMJE	AKF-371; EudraCT no: 2006-001976-19
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor ICMJE	University of Southern Denmark
Collaborators ICMJE	H. Lundbeck A/S
Investigators ICMJE	Principal Investigator: Kim Brosen, dr. med. University of Southern Denmark
PRS Account	University of Southern Denmark
Verification Date	February 2008
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP