Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00397059
Recruitment Status : Completed
First Posted : November 8, 2006
Last Update Posted : February 6, 2008
H. Lundbeck A/S
Information provided by:
University of Southern Denmark

Brief Summary:
To study the impact of CYP2C19 polymorphism on escitalopram pharmacokinetics and pharmacodynamics measured as changes in pupil diameter

Condition or disease Intervention/treatment Phase
Healthy Drug: Escitalopram Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Pupillary Changes as a Potential Biomarker for Escitalopram in Relation to CYP2C19 Polymorphism
Study Start Date : December 2006
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Dynamic pupillometry
  2. Pharmacokinetics
  3. AUC

Secondary Outcome Measures :
  1. Cmax
  2. Tmax

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Healthy volunteer
  • Age: 18-45 years
  • Phenotyped for CYP2C19 activity

Exclusion Criteria:

  • Drug or alcohol abuse
  • Allergy towards escitalopram

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00397059

Layout table for location information
Clinical Pharmacology, University of Southern Denmark
Odense, Denmark, DK-5000
Sponsors and Collaborators
University of Southern Denmark
H. Lundbeck A/S
Layout table for investigator information
Principal Investigator: Kim Brosen, dr. med. University of Southern Denmark

Layout table for additonal information Identifier: NCT00397059    
Other Study ID Numbers: AKF-371
EudraCT no: 2006-001976-19
First Posted: November 8, 2006    Key Record Dates
Last Update Posted: February 6, 2008
Last Verified: February 2008
Keywords provided by University of Southern Denmark:
healthy volunteers
Additional relevant MeSH terms:
Layout table for MeSH terms
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents