Official Title: “Blood-Brain-Barrier Permeability of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-Gene: Effect on Sleep and Procedural Learning”

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.

Study Type: Interventional

Study Design: Basic Science, Open Label, Parallel Assignment

Study Primary Completion Date: March 2009

Intervention(s) in this Clinical Trial

• Drug: escitalopram
  • escitalopram 10 mg

Arms, Groups and Cohorts in this Clinical Trial

• Other: 1
  • Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A)
• Other: 2
  • Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B)

Primary Measures

• Brain levels of escitalopram as assessed by a 19-F magnetic resonance spectroscopy
  • Time Frame: after 6 takes of intake of escitalopram
    Safety Issue?: No

Secondary Measures

• Sleep-EEG, functional MRI, learning, gene expression, metabolic changes
  • Time Frame: after 6 days of intake of escitalopram
    Safety Issue?: No

Inclusion Criteria:

• healthy males 20-30 years and 50-60 years

Exclusion Criteria:

• any medication

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Max-Planck-Institute of Psychiatry

Overall Clinical Trial Officials and Contacts

Axel Steiger, MD Principal Investigator Max-Planck-Institute of Psychiatry  

Overall Contact: Axel Steiger, MD 0049 8930622 steiger@mpipsykl.mpg.de

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00550485

Study ID Number: L3/2005

ClinicalTrials.gov Identifier: NCT00550485

Health Authority: Germany: Federal Institute for Drugs and Medical Devices