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REward Processing And Citalopram Study (REPAC)

Primary Purpose

Anhedonia

Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Citalopram 20mg
Placebo
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anhedonia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Participant is willing and able to give informed consent for participation in the research Aged between 18 to 65 years Sufficient knowledge of English language to understand and complete study tasks Exclusion Criteria: Current or past probable diagnosis of psychiatric illness, according to DSM-5 criteria, requiring intervention by a healthcare professional, including but not limited to psychosis, bipolar disorder, major depression, OCD, PTSD, substance abuse disorder or any eating disorder Current or past diagnosis of any significant personality disorder (e.g. borderline personality disorder) according to self-report Diagnosis of attention deficit hyperactive disorder or autistic spectrum disorder that impairs daily functioning, requires pharmacotherapy or in the opinion of the study medic would affect the scientific integrity of the study Current use of medication that might interact with the effects of citalopram or affect the scientific integrity of the study Previous suicide attempt or previous prolonged period (e.g. > 5 days) of thoughts to end life Known contraindication to citalopram including: past allergic reaction to citalopram or any other medicines, diagnosis of a cardiovascular condition, glaucoma, type 1 or type 2 diabetes, diagnosis of epilepsy, previous diagnosis of angle-closure glaucoma, or current use of any other medication whose use interacts with citalopram (according to BNF guidance) e.g. associated with prolonged QT-interval Any other current or past medical conditions which in the opinion of the study medic may interfere with the safety of the participant or the scientific integrity of the study including epilepsy/seizures, brain injury, hepatic or renal disease, diabetes, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder Severely underweight (BMI<17) or very obese (BMI>40) in a manner that renders them unsuitable for the study in the opinion of the study medic Heavy use of cigarettes (smoke > 20 cigarettes per day) Heavy use of caffeine (drink > 4 250ml cups/cans of coffee/energy drinks per day) Lactose intolerance (due to the study involving administration of a lactose placebo tablet) Known allergy to citric acid, sodium chloride, sucrose or quinine Pregnancy (as determined by urine pregnancy test taken during the Part 2 screening visit), breast feeding or plans to become pregnant past history of dependence on illicit substances or regular illicit substance use within previous three months Evidence of current or past harmful use of alcohol previous participation in a study involving the tasks used in this study or involving use of citalopram in the last year physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging ongoing deficit in sense of smell or taste e.g. following Covid-19 infection Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator Not suitable for MRI neuroimaging e.g. claustrophobia, difficulty remaining still for duration of scan Any MRI contraindications outlined in FMRIB 3 Tesla scanning safety form

Sites / Locations

  • Neurosciences building, Department of Psychiatry, Warneford hospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Citalopram

Placebo

Arm Description

Citalopram 20mg p.o. once daily for 7-9 days

Lactose p.o. once daily for 7-9 days

Outcomes

Primary Outcome Measures

Reward & aversive learning: behavioural correlates
Optimal choice learning rate of conditioned stimuli to win and loss outcomes. During an instrumental reinforcement learning task participant will complete trials with a pair of symbols (the valence will either be loss or win, which is implicit). One symbol will be high chance of that outcome (either win or loss depending on the valence of the pair) and the other low chance of the outcome. In the win pair the optimal choice is the high chance symbol (i.e. to win), in the loss pair the optimal choice is the low chance option (i.e. avoid loss). In each allocation group the proportion of participants making an optimal choice will be calculated on a trial-by-trial basis. This provide the learning rate outcome.
Reward & aversive learning: neural correlates
Activity of a network of brain regions associated with reward learning (during anticipation and outcome), in response to a positive & negative outcomes in reward learning task. This will be the difference in BOLD activation in certain brain regions (pertinent to reward processing) between allocation groups during the anticipation stage and the outcome stage of the instrumental learning task.

Secondary Outcome Measures

Resting state
Resting state fMRI activation
Subjective rating of primary reward
Subjective rating of four tastes (sweet, salt, sour & bitter) in terms of intensity, anticipation of pleasurableness and actual pleasurableness.
Reward & aversive learning: behavioural volatile reward learning task: total money won
Amount of money won/lost & total amount of money received.
Motivational reward task
Participants are asked to accept or decline hypothetical offers made of various combinations of reward and physical effort (grip strength). For a limited number of offers participants are asked to actually expend effort for offers too. The investigators will examine Proportion of offer acceptance for various levels of reward and effort proportion of accepted offers successfully obtained
Reward & aversive learning: behavioural volatile reward learning task: learning rate
Learning rate of optimal choices changes during the task. Proportion of participants in each allocation arm making an optimal choice on a trial-by-trial basis will provide the learning rate for each group. Provides sensitive measure of reward and aversive learning rates.

Full Information

First Posted
May 15, 2023
Last Updated
August 23, 2023
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT06017037
Brief Title
REward Processing And Citalopram Study
Acronym
REPAC
Official Title
REward Processing And Citalopram Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this experimental medicine study is to examine the effect of increasing serotonin on reward processing in healthy volunteers. The main questions it aims to answer are: Does a subacute increase in serotonin influence the activation regions during reward learning Does a subacute increase in serotonin influence behavioural markers of reward valuation (effort task), responsiveness (taste task) and learning (learning task) Participants will be: given a 7-day course of the selective serotonin reuptake inhibitor, citalopram. undergo behavioural testing complete a reward learning task whilst undergoing fMRI Researchers will compare results against a placebo group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anhedonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Citalopram
Arm Type
Experimental
Arm Description
Citalopram 20mg p.o. once daily for 7-9 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Lactose p.o. once daily for 7-9 days
Intervention Type
Drug
Intervention Name(s)
Citalopram 20mg
Intervention Description
Citalopram 20mg tablets, encapsulated to aid blinding. To take per oral once daily for 7-9 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Lactose monohydrate tablets encapsulated to aid blinding. To take per oral once daily for 7-9 days
Primary Outcome Measure Information:
Title
Reward & aversive learning: behavioural correlates
Description
Optimal choice learning rate of conditioned stimuli to win and loss outcomes. During an instrumental reinforcement learning task participant will complete trials with a pair of symbols (the valence will either be loss or win, which is implicit). One symbol will be high chance of that outcome (either win or loss depending on the valence of the pair) and the other low chance of the outcome. In the win pair the optimal choice is the high chance symbol (i.e. to win), in the loss pair the optimal choice is the low chance option (i.e. avoid loss). In each allocation group the proportion of participants making an optimal choice will be calculated on a trial-by-trial basis. This provide the learning rate outcome.
Time Frame
Day 7-9 of treatment
Title
Reward & aversive learning: neural correlates
Description
Activity of a network of brain regions associated with reward learning (during anticipation and outcome), in response to a positive & negative outcomes in reward learning task. This will be the difference in BOLD activation in certain brain regions (pertinent to reward processing) between allocation groups during the anticipation stage and the outcome stage of the instrumental learning task.
Time Frame
Day 7-9 of treatment
Secondary Outcome Measure Information:
Title
Resting state
Description
Resting state fMRI activation
Time Frame
Day 7-9 of treatment
Title
Subjective rating of primary reward
Description
Subjective rating of four tastes (sweet, salt, sour & bitter) in terms of intensity, anticipation of pleasurableness and actual pleasurableness.
Time Frame
Day 0 and day 7-9 of treatment
Title
Reward & aversive learning: behavioural volatile reward learning task: total money won
Description
Amount of money won/lost & total amount of money received.
Time Frame
day 7-9 of treatment
Title
Motivational reward task
Description
Participants are asked to accept or decline hypothetical offers made of various combinations of reward and physical effort (grip strength). For a limited number of offers participants are asked to actually expend effort for offers too. The investigators will examine Proportion of offer acceptance for various levels of reward and effort proportion of accepted offers successfully obtained
Time Frame
day 7-9 of treatment
Title
Reward & aversive learning: behavioural volatile reward learning task: learning rate
Description
Learning rate of optimal choices changes during the task. Proportion of participants in each allocation arm making an optimal choice on a trial-by-trial basis will provide the learning rate for each group. Provides sensitive measure of reward and aversive learning rates.
Time Frame
day 7-9 of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participant is willing and able to give informed consent for participation in the research Aged between 18 to 65 years Sufficient knowledge of English language to understand and complete study tasks Exclusion Criteria: Current or past probable diagnosis of psychiatric illness, according to DSM-5 criteria, requiring intervention by a healthcare professional, including but not limited to psychosis, bipolar disorder, major depression, OCD, PTSD, substance abuse disorder or any eating disorder Current or past diagnosis of any significant personality disorder (e.g. borderline personality disorder) according to self-report Diagnosis of attention deficit hyperactive disorder or autistic spectrum disorder that impairs daily functioning, requires pharmacotherapy or in the opinion of the study medic would affect the scientific integrity of the study Current use of medication that might interact with the effects of citalopram or affect the scientific integrity of the study Previous suicide attempt or previous prolonged period (e.g. > 5 days) of thoughts to end life Known contraindication to citalopram including: past allergic reaction to citalopram or any other medicines, diagnosis of a cardiovascular condition, glaucoma, type 1 or type 2 diabetes, diagnosis of epilepsy, previous diagnosis of angle-closure glaucoma, or current use of any other medication whose use interacts with citalopram (according to BNF guidance) e.g. associated with prolonged QT-interval Any other current or past medical conditions which in the opinion of the study medic may interfere with the safety of the participant or the scientific integrity of the study including epilepsy/seizures, brain injury, hepatic or renal disease, diabetes, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder Severely underweight (BMI<17) or very obese (BMI>40) in a manner that renders them unsuitable for the study in the opinion of the study medic Heavy use of cigarettes (smoke > 20 cigarettes per day) Heavy use of caffeine (drink > 4 250ml cups/cans of coffee/energy drinks per day) Lactose intolerance (due to the study involving administration of a lactose placebo tablet) Known allergy to citric acid, sodium chloride, sucrose or quinine Pregnancy (as determined by urine pregnancy test taken during the Part 2 screening visit), breast feeding or plans to become pregnant past history of dependence on illicit substances or regular illicit substance use within previous three months Evidence of current or past harmful use of alcohol previous participation in a study involving the tasks used in this study or involving use of citalopram in the last year physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging ongoing deficit in sense of smell or taste e.g. following Covid-19 infection Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator Not suitable for MRI neuroimaging e.g. claustrophobia, difficulty remaining still for duration of scan Any MRI contraindications outlined in FMRIB 3 Tesla scanning safety form
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Smith, MBBS
Phone
07865 618318
Email
alexander.smith@psych.ox.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Susannah Murphy, PhD
Email
susannah.murphy@psych.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Harmer, PhD
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurosciences building, Department of Psychiatry, Warneford hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7JX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexander Smith
Phone
01865618339
Email
Alexander.Smith@psych.ox.ac.uk
First Name & Middle Initial & Last Name & Degree
Catherine harmer
Email
catherine.harmer@psych.ox.ac.uk

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Research data will be anonymised and then processed for analysis. Anonymised data will be made available post-publication on Open Science Framework (OSF). defaced neural images will be shared via governed access through Zenodo with data sharing agreements in place

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REward Processing And Citalopram Study

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