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

NCT00550485 | Completed

• 1 other identifier: L3/2005
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Sleep stages

  after 6 days of intake of escitalopram

• Sleep continuity

  after 6 days of intake of escitalopram

• ABCB1 gene expression

  baseline and after 6 days of intake of escitalopram

• Metabolic changes

  baseline and after 6 days of intake of escitalopram

Study Arms (2)

1

OTHER

Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A)

Drug: escitalopram

2

OTHER

Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B)

Drug: escitalopram

Interventions

escitalopram DRUG

escitalopram 4 mg

1; 2

Eligibility Criteria

• Age: 20 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy males 20-30 years

You may not qualify if:

• any medication

Sponsors & Collaborators

• Max-Planck-Institute of Psychiatry: lead

Study Sites (1)

Max Planck Institute of Psychiatry

Munich, 81667, Germany

Location

MeSH Terms

Interventions

Escitalopram

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Axel Steiger, MD

  Max-Planck-Institute of Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: October 30, 2007
• Study Start: October 1, 2007
• Primary Completion: July 6, 2018
• Study Completion: July 6, 2018
• Last Updated: March 27, 2019

Record last verified: 2019-03

Locations

DE (1)