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
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
Scientific
Max Planck Institute for Human Cognitive and Brain Sciences
Stephanstrasse 1A
Leipzig
04103
Germany
| Phone | +49 (0)341 9940-2409 |
|---|---|
| sacher@cbs.mpg.de |
Public
Max Planck Institute for Human Cognitive and Brain Sciences
Department of Neurology
Stephanstraße 1A
Leipzig
04103
Germany
| Phone | +49 7071 29-85736 |
|---|---|
| lewis@cbs.mpg.de |
Study information
| Study design | Single-centre double-blind placebo-controlled crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | Acute 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 acronym | SEROTONIN |
| Study objectives | Hypothesis 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) studied | Effects of the antidepressant escitalopram in healthy volunteers |
| Intervention | The 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 type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Escitalopram |
| Primary outcome measure | Structural, functional, and resting-state MRI data measured during baseline, placebo, and drug sessions |
| Secondary outcome measures | 1. 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 date | 11/10/2011 |
| Completion date | 31/12/2018 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 20 |
| Total final enrolment | 24 |
| Key inclusion criteria | 1. 20-30 years of age 2. Naive to antidepressants |
| Key exclusion criteria | 1. 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 enrolment | 01/11/2011 |
| Date of final enrolment | 30/04/2013 |
Locations
Countries of recruitment
- Germany
Study participating centre
Leipzig
04103
Germany
Sponsor information
Research organisation
Stephanstrasse 1A
Leipzig
04103
Germany
| Phone | +49 341 9940-00 |
|---|---|
| info@cbs.mpg.de | |
| Website | https://www.cbs.mpg.de/en |
Funders
Funder type
Research organisation
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 date | 01/06/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | The 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 plan | The 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.
