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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00397059
First Posted: November 8, 2006
Last Update Posted: February 6, 2008
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.
Collaborator:
H. Lundbeck A/S
Information provided by:
University of Southern Denmark
  Purpose
To study the impact of CYP2C19 polymorphism on escitalopram pharmacokinetics and pharmacodynamics measured as changes in pupil diameter

Condition Intervention Phase
Healthy Drug: Escitalopram Phase 4

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University of Southern Denmark:

Primary Outcome Measures:
  • Dynamic pupillometry
  • Pharmacokinetics
  • AUC

Secondary Outcome Measures:
  • Cmax
  • Tmax


Estimated Enrollment: 16
Study Start Date: December 2006
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Drug or alcohol abuse
  • Allergy towards escitalopram
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00397059


Locations
Denmark
Clinical Pharmacology, University of Southern Denmark
Odense, Denmark, DK-5000
Sponsors and Collaborators
University of Southern Denmark
H. Lundbeck A/S
Investigators
Principal Investigator: Kim Brosen, dr. med. University of Southern Denmark
  More Information

ClinicalTrials.gov Identifier: NCT00397059     History of Changes
Other Study ID Numbers: AKF-371
EudraCT no: 2006-001976-19
First Submitted: November 6, 2006
First Posted: November 8, 2006
Last Update Posted: February 6, 2008
Last Verified: February 2008

Keywords provided by University of Southern Denmark:
Escitalopram
Pharmacokinetics
Pharmacodynamics
CYP2C19
Pupillometry
healthy volunteers

Additional relevant MeSH terms:
Citalopram
Dexetimide
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
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents