Pharmacokinetic and Pharmacodynamic Effects of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene

Study Overview
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Brief Summary
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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 central nervous system. 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. Sleep recordings are a useful bio-marker for effects of antidepressants on the CNS. Selective serotonin 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, effects of drug intake on the gene expression in lymphocytes and metabolic changes will be assessed.

Official Title
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Blood-brain-barrier Permeability of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene: Effect on Sleep and Procedural Learning

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: escitalopram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy males 20-30 years Exclusion Criteria: any medication

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A) | Drug: escitalopram<br>* escitalopram 4 mg<br>|
| Other: 2<br>Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B) | Drug: escitalopram<br>* escitalopram 4 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography. | Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography. | after 6 days of intake of escitalopram | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep stages | Sleep stages beside REM sleep (wake, NonREM sleep) assessed by polysomnography | after 6 days of intake of escitalopram | 
| Sleep continuity | Sleep continuity measures assessed by polysomnography | after 6 days of intake of escitalopram | 
| ABCB1 gene expression | messenger ribonucleic acid (mRNA) expression of the target gene ABCB1 | baseline and after 6 days of intake of escitalopram | 
| Metabolic changes | Small molecule metabolic changes in blood serum | baseline and after 6 days of intake of escitalopram |