Acute serotonergic modulation of brain regions and behaviors implicated in mood regulation

ISRCTN ISRCTN10650334
DOI https://doi.org/10.1186/ISRCTN10650334
EudraCT/CTIS number 2019-003470-12
Secondary identifying numbers NRO-080
Submission date
05/12/2019
Registration date
10/03/2020
Last edited
10/03/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Mental and Behavioural Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Selective serotonin reuptake inhibitors (SSRIs) are considered first-line treatment in depression. However, the exact mechanism of this drug is still not fully understood today. The aim of this study is to investigate the effect of a single oral dose of SSRIs on brain and behavior and compare it to placebo (dummy drug) in healthy volunteers.

Who can participate?
Female and male healthy volunteers between 20 and 30 years of age

What does the study involve?
All participants receive a single oral dose of the SSRI escitalopram and placebo. One group receives escitalopram first and then undergoes a magnetic resonance imaging (MRI) scan 3-4 hours later. After a wash-out period of 8 weeks, this group of participants receives a placebo pill and then again undergoes MRI. A second group starts with the placebo pill and then, after 8 weeks, receives escitalopram. Neither the participants nor the experimenter will know if the participants receive the escitalopram or the placebo pill. Only after the study has finished will the experimenter learn the treatment orders. Before each MRI scan session, participants fill out questionnaires assessing depression and mood.

What are the possible benefits and risks of participating?
Participants receive financial compensation for taking part in the study. A single oral dose of SSRI rarely has minimal temporary side effects, such as nausea, changes in sleep, less sexual arousal, restlessnees, or headaches. MRI scanning does not have harmful effects, only rarely may participants experience circulatory problems.

Where is the study run from?
Max Planck Institute for Human Cognitive and Brain Sciences (Germany)

When is the study starting and how long is it expected to run for?
October 2011 to April 2013

Who is funding the study?
Max Planck Institute for Human Cognitive and Brain Sciences (Germany)

Who is the main contact?
Dr Julia Sacher
sacher@cbs.mpg.de

Contact information

Dr Julia Sacher
Scientific

Max Planck Institute for Human Cognitive and Brain Sciences
Stephanstrasse 1A
Leipzig
04103
Germany

Phone +49 (0)341 9940-2409
Email sacher@cbs.mpg.de
Ms Carolin Lewis
Public

Max Planck Institute for Human Cognitive and Brain Sciences
Department of Neurology
Stephanstraße 1A
Leipzig
04103
Germany

Phone +49 7071 29-85736
Email lewis@cbs.mpg.de

Study information

Study designSingle-centre double-blind placebo-controlled crossover study
Primary study designInterventional
Secondary study designRandomised cross over trial
Study setting(s)Other
Study typeOther
Participant information sheet Not available in web format, please use contact details to request a participant information sheet.
Scientific titleAcute serotonergic modulation of intrinsic functional connectivity and function in brain regions and behaviors implicated in mood regulation - a pharmacological fMRI study in healthy volunteers
Study acronymSEROTONIN
Study objectivesHypothesis 1: It is hypothesized that an acute serotonergic challenge has a large-scale impact on the intrinsic functional connectivity of most cortical and subcortical areas and is not limited to specific networks.

Hypothesis 2: It is hypothesized that an acute serotonergic challenge alters BOLD response in main areas of the reward system and explore, whether these early alterations affect only responses to punishment or responses to both reward and punishment.

Hypothesis 3: It is hypothesized that an acute serotonergic challenge alters BOLD response in amygdala and explore, whether this affects cognitive performance and emotional distraction.
Ethics approval(s)Approved 11/10/2010, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig (ethics board of the Medical Faculty of the University of Leipzig, Käthe-Kollwitz-Straße 82, 04109 Leipzig, Germany; Tel: +49 (0)341/97 154 90; Email: ethik@medizin.uni-leipzig.de), ref: 246-2009-09112009
Health condition(s) or problem(s) studiedEffects of the antidepressant escitalopram in healthy volunteers
InterventionThe researchers administer a single oral dose of 20 mg escitalopram, a selective serotonin reuptake inhibitor (SSRI), or placebo to healthy participants in a double-blind, placebo-controlled, crossover design. Two treatment orders are randomly assigned to participants to ensure complete balancing of treatments. Escitalopram or placebo are administered at two different test days separated by a wash-out period of 8 weeks. At the first test day, participants undergo a baseline MRI scan before initial drug administration. For the drug MRI scans, the researchers measure participants 3-4 hours after drug administration, during peak concentration of escitalopram in blood. Scanning time is approx. 60 minutes per scan, consisting of structural MRI, resting state fMRI, and functional MRI (cognitive load task and reward task). Before each scan session, participants fill out questionnaires assessing depression (Hamilton Rating Scale for Depression) and mood (Profile of Mood states, and MOODS spectrum self-report).
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Escitalopram
Primary outcome measureStructural, functional, and resting-state MRI data measured during baseline, placebo, and drug sessions
Secondary outcome measures1. Reward and punishment processing measured using a monetary reward task, which participants perform during the functional MRI scans at baseline, placebo, and drug sessions
2. Cognitive performance measured using a cognitive load task, which participants perform during the functional MRI scans at baseline, placebo, and drug sessions
Overall study start date11/10/2011
Completion date31/12/2018

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
SexBoth
Target number of participants20
Total final enrolment24
Key inclusion criteria1. 20-30 years of age
2. Naive to antidepressants
Key exclusion criteria1. Current or past psychiatric diagnosis as assessed with SKID-I and SKID-II interview
2. Major head trauma or neurological disease, current or in history
3. Use of psychotropic medication or of recreational drugs
4. MRI contraindications such as metal implants, claustrophobia, pregnancy
5. Smoking
6. Irregular sleep/wake rhythm (e.g., regular nightshifts or cross timeline travel)
Date of first enrolment01/11/2011
Date of final enrolment30/04/2013

Locations

Countries of recruitment

  • Germany

Study participating centre

Max Planck Institute for Human Cognitive and Brain Sciences
Stephanstrasse 1A
Leipzig
04103
Germany

Sponsor information

Max Planck Institute for Human Cognitive and Brain Sciences
Research organisation

Stephanstrasse 1A
Leipzig
04103
Germany

Phone +49 341 9940-00
Email info@cbs.mpg.de
Website https://www.cbs.mpg.de/en

Funders

Funder type

Research organisation

Max-Planck-Institut für Kognitions- und Neurowissenschaften
Private sector organisation / Other non-profit organizations
Alternative name(s)
Max Planck Institute for Human Cognitive and Brain Sciences, MPI for Human Cognitive and Brain Sciences
Location
Germany

Results and Publications

Intention to publish date01/06/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryStored in repository
Publication and dissemination planThe publication in the publications list includes the results of this study (results for hypothesis 1). Publication of the functional imaging results (hypothesis 2 and 3) is currently ongoing - planned publication in a high-impact peer-reviewed journal.
IPD sharing planThe datasets generated during and/or analysed during the current study will be stored in a repository
Type of data: Statistic maps of functional connectivity analysis
Repository name: Neurovault.org
Weblink: https://identifiers.org/neurovault.collection:190
Process for requesting access: freely available
Consent from participants: Participants gave their consent that the results of this study will be published for scientific purposes.
Data anonymization: pseudonymised

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 06/10/2014 16/12/2019 Yes No

Editorial Notes

16/12/2019: Trial's existence confirmed by ethics board of the Medical Faculty of the University of Leipzig.