Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response
Primary Purpose
Depression
Status
Completed
Phase
Phase 4
Locations
Austria
Study Type
Interventional
Intervention
Escitalopram
Sponsored by
About this trial
This is an interventional basic science trial for Depression focused on measuring major depressive disorder, MDD, imaging genetics, pharmacoMRI
Eligibility Criteria
Inclusion Criteria:
- Male or female
- Age 18 -45 years
- Right-handedness
- DSM-IV diagnosis of a major depressive episode (SCID)
- a MADRS score ≥20 and ≤ 30
- ability to be managed as outpatients
- ability to fulfill the criteria to undergo an MRI scan
- Caucasian subjects of European ancestry
Exclusion Criteria:
- previous or concurrent major medical or neurological illness
- clinically significant abnormal values in routine laboratory screening or general physical examination
- DSM-IV diagnosis of substance dependence within the past year, except for caffeine or nicotine or current substance abuse
- DSM-IV diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or an anxiety disorder as a primary diagnosis
- the use of any psychotropic drug within the last two months unresponsiveness of a former major depressive episode to an adequate antidepressive drug dosing of at least 6 weeks duration or any kind of therapy resistance
- a history of severe drug allergy or hypersensitivity or known hypersensitivity to escitalopram
- being acutely suicidal either indicated by a score ≥ 5 on item 10 (suicidal thoughts) on the MADRS or a score ≥ 4 on the HAM-D 21 (suicidal thoughts) or according to the investigator´s opinion
- failures to comply with the study protocol or to follow the instructions of the investigating team
- current pregnancy or breast feeding
- metallic implants or other contraindications to MRI
Sites / Locations
- Medical University of Vienna, Dept. of Psychiatry and Psychotherapy
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Escitalopram
Arm Description
Escitalopram, p.o., 10 mg/d; optional 20 mg/d after 2 weeks for 8 weeks
Outcomes
Primary Outcome Measures
BOLD signal
Secondary Outcome Measures
Full Information
NCT ID
NCT01251471
First Posted
December 1, 2010
Last Updated
October 28, 2016
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT01251471
Brief Title
Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response
Official Title
Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response
Study Type
Interventional
2. Study Status
Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The aim of this pharmaco-MRI study is to investigate neural correlates of variable antidepressant treatment response driven by genetic variation in multiple genes involved in depression.
Thirty Major Depressive Disorder (MDD) patients with a concurrent major depressive episode will undergo three MRI scanning sessions after escitalopram treatment initiation. Furthermore, extensive behavioral assessments and measures of potential peripheral markers such lymphocyte mRNA or pharmacological parameters on platelets or lymphocytes will be performed.
Imaging measures have been suggested to be superior for drug response assessment as compared to psychometric scales, which hardly correlate with biological parameters. Since imaging techniques are too expensive and sophisticated for a broad clinical use, this study will provide pilot data on potential peripheral biomarkers of neural activation being related to drug response.
Detailed Description
The aim of this pharmaco-MRI study is to investigate neural correlates of variable antidepressant treatment response driven by genetic variation in multiple genes involved in depression.
Thirty Major Depressive Disorder (MDD) patients with a concurrent major depressive episode will undergo three MRI scanning sessions at baseline, 4 hours and 8 weeks after escitalopram treatment initiation. During each MRI session, one structural and 3 fMRI scans each engaging different brain circuitries will be performed. All subjects will undergo extensive behavioral assessment and will be genotyped. Furthermore, potential peripheral markers such lymphocyte mRNA or pharmacological parameters on platelets or lymphocytes will be assessed.
The investigators expect that genetic variants which have been associated with variable response to SSRIs in previous Imaging Genetics studies are modulating neural targets of drug response. Moreover, peripheral markers are expected to correlate with these brain region measurements.
Imaging measures have been suggested to be superior for drug response assessment as compared to psychometric scales, which hardly correlate with biological parameters. Since imaging techniques are too expensive and sophisticated for a broad clinical use, this study will provide pilot data on peripheral biomarkers of neural activation being related to drug response. Furthermore, this study will demonstrate whether and how genotypes impact on the dynamics of neural drug response in vivo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression
Keywords
major depressive disorder, MDD, imaging genetics, pharmacoMRI
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Escitalopram
Arm Type
Experimental
Arm Description
Escitalopram, p.o., 10 mg/d; optional 20 mg/d after 2 weeks for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Other Intervention Name(s)
Lexapro, Cipralex, Seroplex, Lexamil
Intervention Description
10 mg/d; optional 20 mg/d after 2 weeks.
Primary Outcome Measure Information:
Title
BOLD signal
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female
Age 18 -45 years
Right-handedness
DSM-IV diagnosis of a major depressive episode (SCID)
a MADRS score ≥20 and ≤ 30
ability to be managed as outpatients
ability to fulfill the criteria to undergo an MRI scan
Caucasian subjects of European ancestry
Exclusion Criteria:
previous or concurrent major medical or neurological illness
clinically significant abnormal values in routine laboratory screening or general physical examination
DSM-IV diagnosis of substance dependence within the past year, except for caffeine or nicotine or current substance abuse
DSM-IV diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or an anxiety disorder as a primary diagnosis
the use of any psychotropic drug within the last two months unresponsiveness of a former major depressive episode to an adequate antidepressive drug dosing of at least 6 weeks duration or any kind of therapy resistance
a history of severe drug allergy or hypersensitivity or known hypersensitivity to escitalopram
being acutely suicidal either indicated by a score ≥ 5 on item 10 (suicidal thoughts) on the MADRS or a score ≥ 4 on the HAM-D 21 (suicidal thoughts) or according to the investigator´s opinion
failures to comply with the study protocol or to follow the instructions of the investigating team
current pregnancy or breast feeding
metallic implants or other contraindications to MRI
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lukas Pezawas, MD
Organizational Affiliation
Medical University of Vienna, Dept. of Psychiatry and Psychotherapy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna, Dept. of Psychiatry and Psychotherapy
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Citations:
PubMed Identifier
20156570
Citation
Scharinger C, Rabl U, Sitte HH, Pezawas L. Imaging genetics of mood disorders. Neuroimage. 2010 Nov 15;53(3):810-21. doi: 10.1016/j.neuroimage.2010.02.019. Epub 2010 Feb 13.
Results Reference
background
PubMed Identifier
20816317
Citation
Pezawas L, Meyer-Lindenberg A. Imaging genetics: Progressing by leaps and bounds. Neuroimage. 2010 Nov 15;53(3):801-3. doi: 10.1016/j.neuroimage.2010.08.001. No abstract available.
Results Reference
background
PubMed Identifier
22111678
Citation
Rabl U, Scharinger C, Muller M, Pezawas L. Imaging genetics: implications for research on variable antidepressant drug response. Expert Rev Clin Pharmacol. 2010 Jul;3(4):471-89. doi: 10.1586/ecp.10.35.
Results Reference
background
Links:
URL
http://www.meduniwien.ac.at/psychiatrie/
Description
Dep. Psychiatry and Psychotherapy
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Neural, Genetic, and Peripheral Correlates of SSRI Pharmaco-Response
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