Effects of Seven Day Prucalopride Administration in Healthy Volunteers
Primary Purpose
Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Prucalopride
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Molecular Mechanisms of Pharmacological Action focused on measuring 5-HT4, Prucalopride, Resolor, Functional Magnetic Resonance Imaging (fMRI), Emotional Processing, Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
- Participant is willing and able to give informed consent for participation in the study
- Male or female
- Aged 18-40 years
- Sufficiently fluent English to understand and complete the task
- Right handed
- Body Mass Index in the range of 18-30
- Not currently taking any medications (except the contraceptive pill)
Exclusion Criteria:
- Not fluent in English
- Any past or current Axis 1 DSM-V psychiatric disorder
- Current usage of psychoactive medication (except the contraceptive pill, the Depo-Provera injection or the progesterone implant)
- Current usage of any medication that will influence the MRI scan
- Current or past history of drug or alcohol dependency
- Currently pregnant or breastfeeding
- Study visits due to take place during the pre-menstrual week (female participants asked details of their menstrual cycle to schedule the study outside this week)
- Not right handed
- Body Mass Index outside the range of 18-30
- History of cardiac, thyroid, or liver problems
- An autoimmune disorder
- Current, or a history of, gastro-intestinal disorder or irritable bowel syndrome
- Epilepsy
- Known lactate deficiency or any other problem absorbing lactose, galactose, or glucose
- Participation in a study which uses the same computer tasks as those used in the present study
- Participation in a study that involves the use of a medication within the last three months
- Smoker > 5 cigarettes per day
- Typically drinks > 6 caffeinated drinks per day
- Any contraindication to MRI scanning (e.g. metal objects in the body, pacemakers, significant claustrophobia)
Sites / Locations
- University of Oxford
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Prucalopride
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Recognition of positive and negative facial expressions
Accuracy to recognise positive and negative facial expressions (anger, disgust, fear, happy , sad, surprise)
Performance on Auditory Verbal Learning Task (AVLT)
Accuracy on AVLT (number of items recalled across blocks)
Secondary Outcome Measures
Neural response to emotional faces
Blood Oxygen Level Dependent (BOLD) signal in a network including the amygdala, anterior cingulate cortex, and orbitofrontal cortex
Neural response to novel vs repeated scenes
BOLD signal to scenes that have previously been seen compared to novel scenes in a network including the hippocampus and parahippocampal regions
Reward sensitivity
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT)
Categorisation, recall, and recognition of emotional words
Accuracy and reaction time to categorise positive and negative descriptor words; number of words correctly (hits) and incorrectly (false alarms) recalled and recognised
Vigilance to fearful and happy faces on the Facial Dot Probe Task (FDOT)
Vigilance derived from reaction time
Resting state connectivity
Resting state connectivity (using resting state fMRI) including the default mode network, salience network, affective network, and limbic system, identified via correlations between spontaneous BOLD activity in spatially independent regions while participants are not actively engaged in an experimental task
Relative and global cerebral blood flow
Arterial spin labelling (ASL) global and cerebral blood flow
Visual short term memory on the Oxford Memory Test (OMT)
Proportion of correct probe selections, absolute error for probe location, reaction time, and proportion of misbinding errors
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03572790
Brief Title
Effects of Seven Day Prucalopride Administration in Healthy Volunteers
Official Title
The Effect of Seven Day Prucalopride Administration on Emotional Processing in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
June 11, 2018 (Actual)
Primary Completion Date
May 17, 2019 (Actual)
Study Completion Date
May 17, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will investigate whether seven days administration of the serotonin receptor subtype 4 (5-HT4) partial agonist prucalopride has effects on emotional processing and neural activity in healthy volunteers, compared to placebo administration. Using an experimental medicine approach, the effects of prucalopride on cognitive biomarkers of antidepressant action will be characterised. In a double-blind design, participants will be randomised to receive seven days administration of either prucalopride (1mg daily) or placebo. All participants will come for a Screening visit, Research Visit One (including an MRI scan) and Research Visit Two (including measures of emotional processing and non-emotional cognition). The primary study hypothesis is that seven-day prucalopride administration will have positive effects on emotional processing and reward sensitivity. A secondary hypothesis is that seven-day prucalopride administration will alter non-emotional cognition. Finally, the study will test the hypothesis that seven day prucalopride administration will alter neural activity during an emotional faces task and a memory task.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder, Mood Disorders, Mental Disorders, Antidepressive Agents, Cognition
Keywords
5-HT4, Prucalopride, Resolor, Functional Magnetic Resonance Imaging (fMRI), Emotional Processing, Healthy Volunteers
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomly allocated to one of two groups (prucalopride or placebo). Participants in the prucalopride group will receive 1mg once daily for seven days. Participants in the placebo group will receive a lactose placebo once daily for seven days. Note that the study is not assessing the safety or efficacy of prucalopride, rather it is using prucalopride to assess the behavioural and neural effects of 5-HT4 partial agonists.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prucalopride
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Prucalopride
Other Intervention Name(s)
Resolor
Intervention Description
1mg prucalopride capsule, once daily for seven days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Lactose placebo capsule, once daily for seven days
Primary Outcome Measure Information:
Title
Recognition of positive and negative facial expressions
Description
Accuracy to recognise positive and negative facial expressions (anger, disgust, fear, happy , sad, surprise)
Time Frame
Completed on Day 7
Title
Performance on Auditory Verbal Learning Task (AVLT)
Description
Accuracy on AVLT (number of items recalled across blocks)
Time Frame
Completed on Day 7
Secondary Outcome Measure Information:
Title
Neural response to emotional faces
Description
Blood Oxygen Level Dependent (BOLD) signal in a network including the amygdala, anterior cingulate cortex, and orbitofrontal cortex
Time Frame
Completed on Day 6
Title
Neural response to novel vs repeated scenes
Description
BOLD signal to scenes that have previously been seen compared to novel scenes in a network including the hippocampus and parahippocampal regions
Time Frame
Completed on Day 6
Title
Reward sensitivity
Description
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT)
Time Frame
Completed on Day 7
Title
Categorisation, recall, and recognition of emotional words
Description
Accuracy and reaction time to categorise positive and negative descriptor words; number of words correctly (hits) and incorrectly (false alarms) recalled and recognised
Time Frame
Completed on Day 7
Title
Vigilance to fearful and happy faces on the Facial Dot Probe Task (FDOT)
Description
Vigilance derived from reaction time
Time Frame
Completed on Day 7
Title
Resting state connectivity
Description
Resting state connectivity (using resting state fMRI) including the default mode network, salience network, affective network, and limbic system, identified via correlations between spontaneous BOLD activity in spatially independent regions while participants are not actively engaged in an experimental task
Time Frame
Completed on Day 6
Title
Relative and global cerebral blood flow
Description
Arterial spin labelling (ASL) global and cerebral blood flow
Time Frame
Completed on Day 6
Title
Visual short term memory on the Oxford Memory Test (OMT)
Description
Proportion of correct probe selections, absolute error for probe location, reaction time, and proportion of misbinding errors
Time Frame
Completed on Day 7
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Participant is willing and able to give informed consent for participation in the study
Male or female
Aged 18-40 years
Sufficiently fluent English to understand and complete the task
Right handed
Body Mass Index in the range of 18-30
Not currently taking any medications (except the contraceptive pill)
Exclusion Criteria:
Not fluent in English
Any past or current Axis 1 DSM-V psychiatric disorder
Current usage of psychoactive medication (except the contraceptive pill, the Depo-Provera injection or the progesterone implant)
Current usage of any medication that will influence the MRI scan
Current or past history of drug or alcohol dependency
Currently pregnant or breastfeeding
Study visits due to take place during the pre-menstrual week (female participants asked details of their menstrual cycle to schedule the study outside this week)
Not right handed
Body Mass Index outside the range of 18-30
History of cardiac, thyroid, or liver problems
An autoimmune disorder
Current, or a history of, gastro-intestinal disorder or irritable bowel syndrome
Epilepsy
Known lactate deficiency or any other problem absorbing lactose, galactose, or glucose
Participation in a study which uses the same computer tasks as those used in the present study
Participation in a study that involves the use of a medication within the last three months
Smoker > 5 cigarettes per day
Typically drinks > 6 caffeinated drinks per day
Any contraindication to MRI scanning (e.g. metal objects in the body, pacemakers, significant claustrophobia)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susannah E Murphy, DPhil
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oxford
City
Oxford
ZIP/Postal Code
OX3 7JX
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.perloxford.org
Description
Psychopharmacology and Emotion Research Laboratory
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Effects of Seven Day Prucalopride Administration in Healthy Volunteers
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