Condition category
Mental and Behavioural Disorders
Date applied
01/02/2019
Date assigned
08/02/2019
Last edited
08/02/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Serotonin and dopamine are two chemical messengers in the brain that are likely to be involved in the causes and treatments of anxiety disorders. A group of drugs, selective serotonin reuptake inhibitors (SSRIs), is recommended as first-line treatment for social anxiety disorder. However, it is not well understood how the SSRIs exert their anxiety-reducing effects in the brain. The main aim of the study is to examine changes in brain serotonin and dopamine production, in participants suffering from social anxiety disorder, after treatment with the SSRI escitalopram. Treatment-induced changes in these neurotransmitters will be assessed with positron emission tomography (PET) and related to altered brain activity patterns assessed with functional magnetic resonance imaging (fMRI).

Who can participate?
Men and women between 18-64 years old, suffering from social anxiety disorder (patient group) as well as healthy volunteers (healthy control group).

What does the study involve?
Participants will undergo brain scanning both before and after 9 weeks of treatment with the SSRI escitalopram for individuals with social anxiety disorder. PET scanning is used to assess the production of serotonin and dopamine (2 scans before as well as after treatment). Patterns of brain activity during emotionally relevant tasks, e.g. viewing faces expressing different emotions, will also be recorded with fMRI. Blood and saliva samples will be collected for analyses of biological markers of social anxiety.

What are the possible benefits and risks of participating?
Benefits include free treatment of a potentially serious anxiety conditon. Subjects will also receive a small economic compensation for participating (approximately 280 USD). The risks involved are minimal, i.e. the benefits by far outweigh the risks. During PET scans, participants are exposed to radioactive material, but in low doses that do not affect normal bodily functions. Pregnant or breastfeeding women will not be included. There are also safety issues regarding MRI/fMRI scans, i.e. individuals having metallic materials within the body may not be allowed to participate. Also, individuals having heart pacemakers or having undergone surgery of the heart, may not participate. There may be unwanted side effects such as nausea or diminished libido from the study drug, although previous research indicates that escitalopram is generally well tolerated.

Where is the study run from?
Uppsala University, Sweden.

When is the study starting and how long is it expected to run for?
It is expected that the study will start in February 2019 (recruitment, initial neuroimaging, treatment) for the first subjects enrolled. Neuroimaging assessments will be repeated after 9 weeks of treatment along with clinical assessments. A one-year follow-up (with questionnaires) will also be conducted. The study is expected to be completed, for all participants, by July 2021.

Who is funding the study?
Funding has been provided by the Swedish Research Council and Riksbankens Jubileumsfond - The Swedish Foundation for Humanities and Social Sciences

Who is the main contact?
Professor Tomas Furmark, tomas.furmark@psyk.uu.se

Trial website

www.uppsalabrain.se

Contact information

Type

Scientific

Primary contact

Prof Tomas Furmark

ORCID ID

http://orcid.org/0000-0001-6821-9058

Contact details

Dept. of Psychology
Uppsala university
Box 1225
Uppsala
SE-75142
Sweden
+46184712153
tomas.furmark@psyk.uu.se

Additional identifiers

EudraCT number

2018-000207-17

ClinicalTrials.gov number

Nil known

Protocol/serial number

TF2018

Study information

Scientific title

Serotonin-dopamine interactions in social anxiety disorder

Acronym

Study hypothesis

It is hypothesised that responders (as compared no nonresponders) to treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram will exhibit alleviated social anxiety concomitantly with reduced brain serotonin synthesis capacity, assessed with PET, and reduced threat-related activation of the amygdala assessed with fMRI.

The study further evaluates, with exploratory analyses, how SSRI treatment of social anxiety disorder affects:
- Brain dopamine synthesis capacity assessed with PET
- The balance between serotonin/dopamine synthesis, i.e neurotransmitter interactions
- Functional brain connectivity between the amygdala and prefrontal cortex
- Brain structure, i.e. grey matter volume
- Telomerase activity in leukocytes

Ethics approval

Approved 18/01/2018, Regional Research Ethics Committee, Uppsala (Box 1964, SE-751 49 Uppsala, Sweden; +46 18 4717400; registrator@uppsala.epn.se), ref: 2018/001

Study design

Interventional study; non-randomised, single-group, single-centre evaluation of open-label escitalopram in patients with social anxiety disorder assessed with neuroimaging

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Social anxiety disorder

Intervention

Patients with social anxiety disorder will be treated with escitalopram 20 mg (10 mg first week), 1 tablet/daily, for 9 weeks and assessed with positron emission tomography (PET) as well as functional magnetic resonance imaging (fMRI) before and after treatment. This is a non-randomised open-label trial without treatment control group focusing on SSRI drug effects on brain parameters. Pre-treatment differences between patients and a healthy control group will also be evaluated. The brain parameters to be studied are serotonin and dopamine synthesis capacity (PET), neural activations during emotional fMRI paradigms, functional connectivity patterns, and gray matter volume.

The treatment period is 9 weeks (63 days). Participants have an extra drug supply for another 14 days because the day of the last neuroimaging assessment may vary (hence treatment could be prolonged for a maximum of 14 days). Follow-up assessment with questionnaires will be conducted after 1 year.

Intervention type

Drug

Phase

Not Applicable

Drug names

Escitalopram

Primary outcome measure

Social anxiety, measured using:
1. The Liebowitz Social Anxiety Scale (LSAS), pre- and post-treatment
2. The Clinical Global Impression-Improvement (CGI-I) scale at post-treatment

Secondary outcome measures

Social anxiety measured pre- and post-treatment using:
1. Social Interaction Anxiety Scale (SIAS)
2. Social Phobia Scale (SPS)
3. Social Phobia Screening Questionnaire (SPSQ)
4. Montgomery-Åsberg Depression Rating Scale (MADRS-S)
5. Beck Anxiety Inventory (BAI)
6. Quality of Life Inventory (QOLI)
7. Spielberger state-trait anxiety inventory (STAI-S, STAI-T)

Additional measures for research purposes (not outcome measures):
8. Karolinska Scale of Personality (KSP)
9. NEO-PI-R, personality inventory
10. Temperament and Character Inventory (TCI)
11. Karolinska Sleepiness Scale (KSS)
12. Karolinska Sleep Questionnaire (KSQ)
13. Insomnia Severity Index (ISI)
14. Ritvo Autism and Asperger Diagnostic scale (RAADS-14)
15. Tellegen Absorption Scale (TAS)
16. Mystical Experiences Scale (MES)

Overall trial start date

14/03/2016

Overall trial end date

31/07/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Social anxiety disorder according to DSM-5, must be the main diagnosis as assessed with the structured clinical interview for DSM disorders (SCID) and the MINI interview
2. Otherwise somatically healthy
3. Age 18-64
4. Willingness to participate in a brain imaging trial (giving informed consent)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

24 individuals diagnosed with social anxiety disorder + 24 healhty volunteers (controls)

Participant exclusion criteria

1. Treatment of social anxiety within the three months preceding the study
2. Current serious or dominant psychiatric disorder other than social anxiety disorder (e.g. psychosis, major depressoin, bipolar disorder)
3. Suicidal ideation
4. Chronic use of other prescribed medication that could influence the results (e.g. antidepressants, anxiolytics, certain sleeping pills and herbal drugs like St John's Wort)
5. Abuse of alcohol or narcotics
6. Pregnancy of planned pregnancy during the study period
7. Menopause
8. Previous PET examination
9. Contraindications for MRI investigation (e.g implants or other metal objects in the body, brain and heart operations)
10. Heart insufficiency or previous heart surgery
11. Contraindications for treatment with escitalopram

Recruitment start date

12/02/2019

Recruitment end date

31/07/2021

Locations

Countries of recruitment

Sweden

Trial participating centre

Uppsala university
Dept. of Psychology Box 1225
Uppsala
SE-751 42
Sweden

Sponsor information

Organisation

Uppsala university

Sponsor details

Dept. of Psychology
Box 1225
Uppsala
SE-751 42
Sweden
+46184712153
tomas.furmark@psyk.uu.se

Sponsor type

University/education

Website

https://www.psyk.uu.se/

Funders

Funder type

Research council

Funder name

Vetenskapsrådet

Alternative name(s)

Swedish Research Council, VR, SRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Sweden

Funder name

Riksbankens Jubileumsfond

Alternative name(s)

RJ

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Sweden

Results and Publications

Publication and dissemination plan

Results will be evaluated when all participants have been scanned with PET and fMRI (pre-post treatment) and completed all clinical assessments. Results will be published, soonest possible after data collection has been completed, in established international scientific journals with peer review.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/08/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes