Pharmacokinetic and Pharmacodynamic Effects of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-Gene
Information source: Max-Planck-Institute of Psychiatry
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pharmacokinetics
Intervention: escitalopram (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Max-Planck-Institute of Psychiatry Official(s) and/or principal investigator(s):
Axel Steiger, MD, Principal Investigator, Affiliation: Max-Planck-Institute of Psychiatry
Overall contact:
Axel Steiger, MD, Phone: 0049 8930622, Ext: 236, Email: steiger@mpipsykl.mpg.de
Summary
The ABCB1-gene product P-glycoprotein is an integral membrane protein that actively
transports substrates out of the intracellular compartment. One of the major sites of its
action is the blood-brain-barrier. It is highly expressed in brain capillary endothelial
cells and involved in limiting the access of substrates such as antidepressants to the CNS. A
single nucleotide polymorphism (SNP) of the ABCB1-gene was recently identified showing a
different treatment response to antidepressant drugs depending on the genotype. Therefore, it
is assumed that healthy subjects with different genotypes of that SNP will be associated with
significantly different brain levels of the antidepressant escitalopram after 6 days of
intake. For determining intracerebral escitalopram levels, a 19-F magnetic resonance
spectroscopy will be used. Sleep recordings are a useful bio-marker for effects of
antidepressants on the CNS. Selective 5-HT1-reuptake inhibitors (e. g. escitalopram) cause a
suppression of REM sleep and a stronger fragmentation of sleep compared to untreated
subjects. Higher plasma levels of antidepressants affected the sleep to a greater extent than
lower levels. In line with this finding, we suppose that sleep EEG recordings of healthy
subjects with different genotypes of the above mentioned SNP will be differently affected
after taking 6 days escitalopram. In addition, there is good evidence that sleep is involved
in various forms of memory processing. For example, it has been repeatedly shown that the
performance in motor tasks (procedural learning) is correlated with the amount of stage 2
NonREM and REM sleep, respectively. Hence we hypothesize, that a drug-induced impairment of
sleep (e. g. reduction of REM sleep) is associated with an impairment of procedural learning.
In addition, effects of drug intake on the gene expression in lymphocytes and metabolic
changes will be assessed. Functional magnetic resonance imaging will be applied to detect
potential drug-induced changes of corticolimbic circuitries.
Clinical Details
Official title: Blood-Brain-Barrier Permeability of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-Gene: Effect on Sleep and Procedural Learning
Study design: Basic Science, Open Label, Parallel Assignment
Primary outcome: Brain levels of escitalopram as assessed by a 19-F magnetic resonance spectroscopy
Secondary outcome: Sleep-EEG, functional MRI, learning, gene expression, metabolic changes
Eligibility
Minimum age: 20 Years.
Maximum age: 60 Years.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- healthy males 20-30 years and 50-60 years
Exclusion Criteria:
- any medication
Locations and Contacts
Axel Steiger, MD, Phone: 0049 8930622, Ext: 236, Email: steiger@mpipsykl.mpg.de
Max Planck Institute of Psychiatry, Munich 81667, Germany; Recruiting
Axel Steiger, MD, Phone: 0049 8930622, Ext: 236, Email: steiger@mpipsykl.mpg.de
Michael Kluge, MD, Phone: 0049 8930622, Ext: 396, Email: kluge@mpipsykl.mpg.de
Additional Information
Starting date: October 2007
Ending date: June 2009
Last updated: April 21, 2008
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