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

Not Applicable

Completed

• Conditions: Pharmacokinetics
• Interventions: Drug: escitalopram

• Registration Number: NCT00550485
• Lead Sponsor: Max-Planck-Institute of Psychiatry

Brief 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 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-10-29
• Study First Submitted QC: 2007-10-29
• Study First Posted: 2007-10-30
• Primary Completion: 2018-07-06
• Study Completion: 2018-07-06
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-25
• Last Update Posted: 2019-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 79

Inclusion Criteria

• healthy males 20-30 years

Exclusion Criteria

• any medication

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	escitalopram	Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B)
1	escitalopram	Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A)

Primary Outcome Measures

Name	Time	Method
Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography.	after 6 days of intake of escitalopram	Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Max Planck Institute of Psychiatry; 🇩🇪 Munich, Germany