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

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00550485
• Other study ID #: L3/2005
• Status: Completed
• Phase: N/A
• Start date: October 2007
• Est. completion date: July 6, 2018

Study information

• Verified date: March 2019
• Source: Max-Planck-Institute of Psychiatry
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: July 6, 2018
• Est. primary completion date: July 6, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 30 Years

Eligibility

Inclusion Criteria:

• healthy males 20-30 years

Exclusion Criteria:

• any medication

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• escitalopram
escitalopram 4 mg

Locations

Country	Name	City	State
Germany	Max Planck Institute of Psychiatry	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Max-Planck-Institute of Psychiatry

Country where clinical trial is conducted

Germany, 

Outcome

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