HealthyPhase 4NCT04239339

Serotonergic Modulation of Cognition, Emotion and Brain Activation in Healthy Volunteers

A Phase 4 study testing Escitalopram 20 mg in people with Healthy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim of this project is: To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically: To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional… Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Escitalopram 20 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 66 participants
Where: 1 siteDenmark
Study dates: 28 Apr 2020to 30 Oct 2022
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy volunteer (male or female) between 18 and 45 years.

Who cannot join

Current or former primary psychiatric disorder (DSM IV Axis I or WHO ICD-10 diagnostic classification).
Current or previous neurological disease, severe somatic disease, or the consumption of drugs likely to influence the test results.
Non- fluent in Danish or pronounced visual or auditory impairments.
Current or past learning disability.
Pregnancy (females).
Lactation (females).

Show all 20Show fewer

Contraindications for MRI (pacemaker, metal implants, etc.).
Allergy to the ingredients in the administered drug.
Abnormal ECG (e.g. prolonged QT syndrome).
Dizzy when changing from supine to upright position (e.g. postural orthostatic tachycardia syndrome).
Mild hypotension (blood pressure below 100/70 mmHg) or hypertension (blood pressure above 140/90 mmHg).
Head injury or concussion resulting in loss of consciousness for more than 2 min.
Alcohol or drug abuse.
Drug use other than tobacco and alcohol within the last 30 days.
Hash > 50 x lifetime.
Drugs > 10 x lifetime (for each substance).
Nicotine addiction.
Current psychoactive medication.
Severe physical impairments affecting eyesight or motor performance.
Hamilton-6 depression scale score > 5.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

Neurobiology Research Unit
Copenhagen, DK-2100

Other trials in Denmark

About this study

The aim of this project is:

To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.

Read the detailed description

The aim of this project is:

To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.

Serotonin is a monoamine neurotransmitter implicated in diverse cognitive and affective brain functions. Serotonin has a significant role in the regulation of cognition and mood, including emotional appraisal, perception and flexible behaviour, with 5-HT receptors found in the cortex, amygdala and hippocampus. The investigators have previously shown that in healthy human experimental studies, acute dietary tryptophan depletion induces 'waiting' impulsivity and impulsive behaviours, impairs goal-directed behaviour and shifts behavioural control toward habitual responding when appetitive, but goal-directed when aversive. Reduced availability of forebrain serotonin has also shown to impair a range of cognitive processes, such as psychomotor processing, episodic memory, attention and executive function. Recently, the research team have shown that using an acute and clinically relevant dose (20 mg) of escitalopram impaired learning and cognitive flexibility, but improved response inhibition in healthy humans, suggesting a dissociation of effects possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.

The investigators now aim to investigate the effects of sub-chronic administration of 20 mg of escitalopram (i.e. three weeks) in healthy volunteers using sophisticated neuropsychological testing (Cambridge Neuropsychological Test Automated Battery and EMOTICOM) and functional magnetic resonance imaging (fMRI). Whereas 'cold' cognition refers to the use of non-emotional processing (e.g. episodic memory; spatial working memory), 'hot' cognition is emotion-laden and used in response to stimuli with affective salience (e.g. decision-making under high levels of risk of uncertainty). It has been suggested that cognitive-emotional effects, such as the re-appraisal and re-evaluation of emotions underlying learning mechanisms, may mediate improvements in mood associated with SSRI treatment. This project will help further the understanding of the role of serotonin in the regulation of cognitive and emotional processes, as well the neural correlates underlying reinforcement learning, in healthy humans.

Conditions: Healthy
Being tested: Escitalopram 20 mg, Placebo
Keywords: Serotonin, Cognition, Emotion, Neural Activation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Escitalopram 20 mgDrug
20mg daily for approximately 3 weeks.
PlaceboDrug
Placebo daily for approximately 3 weeks.

Study groups in NCT04239339
Study group	Role	What they receive
Control Group	Placebo comparator	The placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo pill. Receives: Drug: Placebo
Intervention Group	Experimental	The intervention group will be administered 20mg of Escitalopram daily for approximately 3 weeks. Receives: Drug: Escitalopram 20 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Learning Primary Outcome 1: Mean errors Stage 1 (Learning) - Probability Reversal Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 years
Learning Primary Outcome 2: Mean errors Stage 2 (Reversal) - Probability Reversal Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Learning Primary Outcome 3: Learning Rate in Reward Trial - Reinforcement Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Learning Primary Outcome 4: Learning Rate in Punishment Trials - Reinforcement Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Inhibition Primary Outcome 1: Stop Signal Reaction Time - Interleaved Stop Signal Task/Go-NoGo.
Outcome variables have been grouped a priori into carefully defined cognitive domains.
Measured: 3 Years
Executive Function Primary Outcome 1: Extra Dimensional Set Errors -3Dimensional Intra/Extra Dimensional Shift.
Outcome variables have been grouped a priori into carefully defined cognitive domains.
Measured: 3 Years
Reinforcement Behaviour Model
A model comparison will be conducted to determine the winning model of reinforcement behaviour using one, a combination of, or all these parameters. The winning model will be a single outcome model.
1. Reward Learning Rate
2. Punishment Learning Rate
3. Reinforcement Sensitivity
4. Stimulus Stickiness
Measured: 3 Years
Social Cognition Primary Outcome 1: Proportion of offers accepted - Ultimatum Game
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Social Cognition Primary Outcome 2: Agent Guilt Score - Moral Emotions Task.
1. Agent Shame Score ---------- Moral Emotions Task Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Social Cognition Primary Outcome 3: Agent Shame Score - Moral Emotions Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Primary Outcome 1: Affective bias in decreasing condition - EMOTICOM Intensity Morphing.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Primary Outcome 2: Affective bias for D' - EMOTICOM Emotion Recognition Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Primary Outcome 3: Detection threshold decreasing - EMOTICOM Intensity Morphing.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Primary Outcome 4: D'Prime for Emotion Recognition - EMOTICOM Emotion Recognition Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Biofluids: Serum Escitalopram levels
Measured: 3 Years
PET Imaging: Cerebral (particularly hippocampal) presynaptic density, as measured with 11 C-UCB-J-PET.
Collected in a sub-sample of participants.
Measured: 3 Years

Secondary outcomes (44)

Learning Secondary Outcome 1: Stage 1 Reward-Stay/Lose-Shift behaviour - Probability Reversal Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Learning Secondary Outcome 2: Stage 2 Reward-Stay/ Lose-Shift behaviour - Probability Reversal Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Learning Secondary Outcome 3: Pre Extra Dimension Set Errors - 3Dimensional Intra/Extra Dimensional Shift.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Learning Secondary Outcome 4: Proportion of Stays - Sequential Model-Based/Model-Free.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Inhibition Secondary Outcome 1: Go reaction time - Interleaved Stop Signal Task/Go-NoGo.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Inhibition Secondary Outcome 2: Go omission error rate - Interleaved Stop Signal Task/Go-NoGo.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Inhibition Secondary Outcome 3: Go commission error rate - Interleaved Stop Signal Task/Go-NoGo.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Inhibition Secondary Outcome 4: No-Go error rate - Interleaved Stop Signal Task/Go-NoGo.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Executive Function Secondary Outcome 1: Total Errors Adjusted - 3Dimensional Intra/Extra Dimensional Shift.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Executive Function Secondary Outcome 2: Strategy Score - CANTAB Spatial Working Memory.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Social Cognition Secondary Outcome 1: Fairness Sensitivity---------- Ultimatum Game
Outcome variables have been grouped a priori into carefully defined cognitive domains.
Measured: 3 Years
Emotion Recognition Secondary Outcome 1: Detection threshold increasing - EMOTICOM Intensity Morphing.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Secondary Outcome 2: Affective bias in increasing condition - EMOTICOM Intensity Morphing.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Secondary Outcome 3: Affective bias for Hit Rate - EMOTICOM Emotion Recognition Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Emotion Recognition Secondary Outcome 4: Hit Rate for Emotion Recognition - EMOTICOM Emotion Recognition Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Faces and geometric figure discrimination Outcome 1: Accuracy - Faces fMRI paradigm
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Faces and geometric figure discrimination Outcome 2: Response Speed - Faces fMRI paradigm.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Memory Outcome 1: Total Errors Adj - CANTAB Paired Associates Learning
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Memory Outcome 2: First Trial Memory Score - CANTAB Paired Associates Learning.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Memory Outcome 3: Between Search Errors - CANTAB Spatial Working Memory.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Attention Outcome 1: Target Sensitivity (A') - CANTAB Rapid Visual Processing.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Attention Outcome 2: Latency - CANTAB Rapid Visual Processing
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Attention Outcome 3: Probability of False Alarms - CANTAB Rapid Visual Processing
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Risky Decision Making Outcome Outcome 1. Quality of Decision Making - EMOTICOM Cambridge Gamble Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Risky Decision Making Outcome 2: Risk Adjustment - EMOTICOM Cambridge Gamble Task
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Risky Decision Making Outcome 3: Overall Proportion Bet - EMOTICOM Cambridge Gamble Task
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Risky Decision Making Outcome 4: Deliberation Time - EMOTICOM Cambridge Gamble Task.
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Psychomotor Speed Outcome 1: Simple reaction time - CANTAB Reaction Time Task
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Psychomotor Speed Outcome 2: Five Choice reaction time - CANTAB Reaction Time Task
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Measured: 3 Years
Neural Activations and Correlations - Reinforcement Learning fMRI paradigm
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
Measured: 3 Years
Neural Activations and Correlations - Faces fMRI paradigm
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
Measured: 3 Years
Resting State fMRI
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
Measured: 3 Years
Structural VBM
Imaging outcomes will be FWE corrected using Random Field Theory as implemented in SPM12.
Measured: 3 Years
Diffusion Tensor Imaging
Measured: 3 Years
Profile of Mood State Score
Measured: 3 Years
Beck Depression Inventory-II Score
Measured: 3 Years
State-Trait Anxiety Inventory Scale -State Score
Measured: 3 Years
State and Trait Aggression Questionnaire-State Score
Measured: 3 Years
Baret Impulsivity Scale-State Score
Measured: 3 Years
Visual Analogue Scale Score
Measured: 3 Years
Interpersonal Reactivity Index Score
Measured: 3 Years
Obsessive- Compulsive Inventory Score
Measured: 3 Years
Brief Symptom Checklist Score
Measured: 3 Years
Pittsburgh Sleep Quality Index Score
Measured: 3 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Apr 202030 Oct 2022

First posted27 Jan 2020
Study start28 Apr 2020
Primary completion30 Oct 2022
Study completion30 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (10)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 66 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04239339
Sponsor's protocol ID: H-18038352
Status last verified: Nov 2023
First submitted: 13 Jan 2020
Last updated: 18 Nov 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Upon completion of the study all data will be uploaded to the existing CIMBI Database. Researchers may apply for access to the data.

Publications

Homberg JR. Serotonin and decision making processes. Neurosci Biobehav Rev. 2012 Jan;36(1):218-36. doi: 10.1016/j.neubiorev.2011.06.001. Epub 2011 Jun 12.
PubMed 21693132
Meneses A. Are 5-HT(1B/1D) and 5-HT(2A/2B/2C) receptors involved in learning and memory processes? IDrugs. 1999 Aug;2(8):796-801.
PubMed 16127655
Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance. Neuropsychopharmacology. 2014 May;39(6):1519-26. doi: 10.1038/npp.2013.351. Epub 2014 Jan 2.
PubMed 24385133
Worbe Y, Savulich G, de Wit S, Fernandez-Egea E, Robbins TW. Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans. Int J Neuropsychopharmacol. 2015 Feb 5;18(10):pyv013. doi: 10.1093/ijnp/pyv013.
PubMed 25663044
Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, Voon V. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016 May;21(5):624-9. doi: 10.1038/mp.2015.46. Epub 2015 Apr 14.
PubMed 25869808
Park SB, Coull JT, McShane RH, Young AH, Sahakian BJ, Robbins TW, Cowen PJ. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology. 1994 Mar-Apr;33(3-4):575-88. doi: 10.1016/0028-3908(94)90089-2.
PubMed 7984295
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718. doi: 10.1093/brain/111.3.695.
PubMed 3382917
Bland AR, Roiser JP, Mehta MA, Schei T, Boland H, Campbell-Meiklejohn DK, Emsley RA, Munafo MR, Penton-Voak IS, Seara-Cardoso A, Viding E, Voon V, Sahakian BJ, Robbins TW, Elliott R. EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition. Front Behav Neurosci. 2016 Feb 24;10:25. doi: 10.3389/fnbeh.2016.00025. eCollection 2016.
PubMed 26941628
Armand S, Langley C, Johansen A, Ozenne B, Overgaard-Hansen O, Larsen K, Jensen PS, Knudsen GM, Sahakian BJ, Stenbaek DS, Fisher PM. Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study. Sci Rep. 2024 Feb 7;14(1):3149. doi: 10.1038/s41598-024-51448-2.
PubMed 38326352
Langley C, Armand S, Luo Q, Savulich G, Segerberg T, Sondergaard A, Pedersen EB, Svart N, Overgaard-Hansen O, Johansen A, Borgsted C, Cardinal RN, Robbins TW, Stenbaek DS, Knudsen GM, Sahakian BJ. Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study. Neuropsychopharmacology. 2023 Mar;48(4):664-670. doi: 10.1038/s41386-022-01523-x. Epub 2023 Jan 23.
PubMed 36683090

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Serotonergic Modulation of Cognition, Emotion and Brain Activation in Healthy Volunteers
ClinicalTrials.gov ID: NCT04239339
Acronym / sponsor ID: H-18038352
Conditions: Healthy
Keywords: Serotonin, Cognition, Emotion, Neural Activation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 66 participants (actual)
Lead sponsor: Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
Collaborators: University of Cambridge, Lundbeck Foundation
Study start: 28 Apr 2020 (actual)
Primary completion: 30 Oct 2022 (actual)
Study completion: 30 Oct 2022 (actual)
First posted: 27 Jan 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The aim of this project is:

To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.

Detailed description

The aim of this project is:

To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Control Group	Placebo comparator	Drug: PlaceboThe placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo pill.
Intervention Group	Experimental	Drug: Escitalopram 20 mgThe intervention group will be administered 20mg of Escitalopram daily for approximately 3 weeks.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Healthy volunteer (male or female) between 18 and 45 years.

Key exclusion criteria (20 listed)

Current or former primary psychiatric disorder (DSM IV Axis I or WHO ICD-10 diagnostic classification).
Current or previous neurological disease, severe somatic disease, or the consumption of drugs likely to influence the test results.
Non- fluent in Danish or pronounced visual or auditory impairments.
Current or past learning disability.
Pregnancy (females).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Escitalopram 20 mg20mg daily for approximately 3 weeks.	Drug	Intervention Group
PlaceboPlacebo daily for approximately 3 weeks.	Drug	Control Group

Primary outcome

Learning Primary Outcome 1: Mean errors Stage 1 (Learning) - Probability Reversal Learning.
Time frame: 3 years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Learning Primary Outcome 2: Mean errors Stage 2 (Reversal) - Probability Reversal Learning.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Learning Primary Outcome 3: Learning Rate in Reward Trial - Reinforcement Learning.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Learning Primary Outcome 4: Learning Rate in Punishment Trials - Reinforcement Learning.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Inhibition Primary Outcome 1: Stop Signal Reaction Time - Interleaved Stop Signal Task/Go-NoGo.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains.
Executive Function Primary Outcome 1: Extra Dimensional Set Errors -3Dimensional Intra/Extra Dimensional Shift.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains.
Reinforcement Behaviour Model
Time frame: 3 Years
A model comparison will be conducted to determine the winning model of reinforcement behaviour using one, a combination of, or all these parameters. The winning model will be a single outcome model. 1. Reward Learning Rate 2. Punishment Learning Rate 3. Reinforcement Sensitivity 4. Stimulus Stickiness
Social Cognition Primary Outcome 1: Proportion of offers accepted - Ultimatum Game
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Social Cognition Primary Outcome 2: Agent Guilt Score - Moral Emotions Task.
Time frame: 3 Years
3. Agent Shame Score ---------- Moral Emotions Task Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Social Cognition Primary Outcome 3: Agent Shame Score - Moral Emotions Task.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Emotion Recognition Primary Outcome 1: Affective bias in decreasing condition - EMOTICOM Intensity Morphing.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Emotion Recognition Primary Outcome 2: Affective bias for D' - EMOTICOM Emotion Recognition Task.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Emotion Recognition Primary Outcome 3: Detection threshold decreasing - EMOTICOM Intensity Morphing.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Emotion Recognition Primary Outcome 4: D'Prime for Emotion Recognition - EMOTICOM Emotion Recognition Task.
Time frame: 3 Years
Outcome variables have been grouped a priori into carefully defined cognitive domains. FDR correction, for multiple comparisons, using the Benjamin Hochberg procedure will be applied to the outcomes within each cognitive domain.
Biofluids: Serum Escitalopram levels
Time frame: 3 Years
PET Imaging: Cerebral (particularly hippocampal) presynaptic density, as measured with 11 C-UCB-J-PET.
Time frame: 3 Years
Collected in a sub-sample of participants.

44 secondary outcomes

Learning Secondary Outcome 1: Stage 1 Reward-Stay/Lose-Shift behaviour - Probability Reversal Learning.
Time frame: 3 Years
Learning Secondary Outcome 2: Stage 2 Reward-Stay/ Lose-Shift behaviour - Probability Reversal Learning.
Time frame: 3 Years
Learning Secondary Outcome 3: Pre Extra Dimension Set Errors - 3Dimensional Intra/Extra Dimensional Shift.
Time frame: 3 Years
Learning Secondary Outcome 4: Proportion of Stays - Sequential Model-Based/Model-Free.
Time frame: 3 Years
Inhibition Secondary Outcome 1: Go reaction time - Interleaved Stop Signal Task/Go-NoGo.
Time frame: 3 Years
Inhibition Secondary Outcome 2: Go omission error rate - Interleaved Stop Signal Task/Go-NoGo.
Time frame: 3 Years
Inhibition Secondary Outcome 3: Go commission error rate - Interleaved Stop Signal Task/Go-NoGo.
Time frame: 3 Years
Inhibition Secondary Outcome 4: No-Go error rate - Interleaved Stop Signal Task/Go-NoGo.
Time frame: 3 Years
Executive Function Secondary Outcome 1: Total Errors Adjusted - 3Dimensional Intra/Extra Dimensional Shift.
Time frame: 3 Years
Executive Function Secondary Outcome 2: Strategy Score - CANTAB Spatial Working Memory.
Time frame: 3 Years
Social Cognition Secondary Outcome 1: Fairness Sensitivity---------- Ultimatum Game
Time frame: 3 Years
Emotion Recognition Secondary Outcome 1: Detection threshold increasing - EMOTICOM Intensity Morphing.
Time frame: 3 Years
Emotion Recognition Secondary Outcome 2: Affective bias in increasing condition - EMOTICOM Intensity Morphing.
Time frame: 3 Years
Emotion Recognition Secondary Outcome 3: Affective bias for Hit Rate - EMOTICOM Emotion Recognition Task.
Time frame: 3 Years
Emotion Recognition Secondary Outcome 4: Hit Rate for Emotion Recognition - EMOTICOM Emotion Recognition Task.
Time frame: 3 Years
Faces and geometric figure discrimination Outcome 1: Accuracy - Faces fMRI paradigm
Time frame: 3 Years
Faces and geometric figure discrimination Outcome 2: Response Speed - Faces fMRI paradigm.
Time frame: 3 Years
Memory Outcome 1: Total Errors Adj - CANTAB Paired Associates Learning
Time frame: 3 Years
Memory Outcome 2: First Trial Memory Score - CANTAB Paired Associates Learning.
Time frame: 3 Years
Memory Outcome 3: Between Search Errors - CANTAB Spatial Working Memory.
Time frame: 3 Years
Attention Outcome 1: Target Sensitivity (A') - CANTAB Rapid Visual Processing.
Time frame: 3 Years
Attention Outcome 2: Latency - CANTAB Rapid Visual Processing
Time frame: 3 Years
Attention Outcome 3: Probability of False Alarms - CANTAB Rapid Visual Processing
Time frame: 3 Years
Risky Decision Making Outcome Outcome 1. Quality of Decision Making - EMOTICOM Cambridge Gamble Task.
Time frame: 3 Years
Risky Decision Making Outcome 2: Risk Adjustment - EMOTICOM Cambridge Gamble Task
Time frame: 3 Years
Risky Decision Making Outcome 3: Overall Proportion Bet - EMOTICOM Cambridge Gamble Task
Time frame: 3 Years
Risky Decision Making Outcome 4: Deliberation Time - EMOTICOM Cambridge Gamble Task.
Time frame: 3 Years
Psychomotor Speed Outcome 1: Simple reaction time - CANTAB Reaction Time Task
Time frame: 3 Years
Psychomotor Speed Outcome 2: Five Choice reaction time - CANTAB Reaction Time Task
Time frame: 3 Years
Neural Activations and Correlations - Reinforcement Learning fMRI paradigm
Time frame: 3 Years
Neural Activations and Correlations - Faces fMRI paradigm
Time frame: 3 Years
Resting State fMRI
Time frame: 3 Years
Structural VBM
Time frame: 3 Years
Diffusion Tensor Imaging
Time frame: 3 Years
Profile of Mood State Score
Time frame: 3 Years
Beck Depression Inventory-II Score
Time frame: 3 Years
State-Trait Anxiety Inventory Scale -State Score
Time frame: 3 Years
State and Trait Aggression Questionnaire-State Score
Time frame: 3 Years
Baret Impulsivity Scale-State Score
Time frame: 3 Years
Visual Analogue Scale Score
Time frame: 3 Years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
Background: PubMed 21693132Homberg JR. Serotonin and decision making processes. Neurosci Biobehav Rev. 2012 Jan;36(1):218-36. doi: 10.1016/j.neubiorev.2011.06.001. Epub 2011 Jun 12.
Background: PubMed 16127655Meneses A. Are 5-HT(1B/1D) and 5-HT(2A/2B/2C) receptors involved in learning and memory processes? IDrugs. 1999 Aug;2(8):796-801.
Background: PubMed 24385133Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance. Neuropsychopharmacology. 2014 May;39(6):1519-26. doi: 10.1038/npp.2013.351. Epub 2014 Jan 2.
Background: PubMed 25663044Worbe Y, Savulich G, de Wit S, Fernandez-Egea E, Robbins TW. Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans. Int J Neuropsychopharmacol. 2015 Feb 5;18(10):pyv013. doi: 10.1093/ijnp/pyv013.
Background: PubMed 25869808Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, Voon V. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016 May;21(5):624-9. doi: 10.1038/mp.2015.46. Epub 2015 Apr 14.
Background: PubMed 7984295Park SB, Coull JT, McShane RH, Young AH, Sahakian BJ, Robbins TW, Cowen PJ. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology. 1994 Mar-Apr;33(3-4):575-88. doi: 10.1016/0028-3908(94)90089-2.
Background: PubMed 3382917Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718. doi: 10.1093/brain/111.3.695.
Background: PubMed 26941628Bland AR, Roiser JP, Mehta MA, Schei T, Boland H, Campbell-Meiklejohn DK, Emsley RA, Munafo MR, Penton-Voak IS, Seara-Cardoso A, Viding E, Voon V, Sahakian BJ, Robbins TW, Elliott R. EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition. Front Behav Neurosci. 2016 Feb 24;10:25. doi: 10.3389/fnbeh.2016.00025. eCollection 2016.
Derived from this study: PubMed 38326352Armand S, Langley C, Johansen A, Ozenne B, Overgaard-Hansen O, Larsen K, Jensen PS, Knudsen GM, Sahakian BJ, Stenbaek DS, Fisher PM. Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study. Sci Rep. 2024 Feb 7;14(1):3149. doi: 10.1038/s41598-024-51448-2.
Derived from this study: PubMed 36683090Langley C, Armand S, Luo Q, Savulich G, Segerberg T, Sondergaard A, Pedersen EB, Svart N, Overgaard-Hansen O, Johansen A, Borgsted C, Cardinal RN, Robbins TW, Stenbaek DS, Knudsen GM, Sahakian BJ. Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study. Neuropsychopharmacology. 2023 Mar;48(4):664-670. doi: 10.1038/s41386-022-01523-x. Epub 2023 Jan 23.
Individual participant dataSharing planned: Yes. Upon completion of the study all data will be uploaded to the existing CIMBI Database. Researchers may apply for access to the data.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Escitalopram 20 mg in people with Healthy, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Learning Primary Outcome 1: Mean errors Stage 1 (Learning) - Probability Reversal Learning. (time frame: 3 years). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04239339, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.