Effects of Seven Day Prucalopride Administration in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Seven Day Prucalopride Administration on Emotional Processing in Healthy Volunteers

Conditions
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Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder, Mood Disorders, Mental Disorders, Antidepressive Agents, Cognition

Intervention / Treatment
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* Drug: Prucalopride
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prucalopride<br> | Drug: Prucalopride<br>* 1mg prucalopride capsule, once daily for seven days<br>* Other names: Resolor;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Lactose placebo capsule, once daily for seven days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recognition of positive and negative facial expressions | Accuracy to recognise positive and negative facial expressions (anger, disgust, fear, happy , sad, surprise) | Completed on Day 7 | 
| Performance on Auditory Verbal Learning Task (AVLT) | Accuracy on AVLT (number of items recalled across blocks) | Completed on Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural response to emotional faces | Blood Oxygen Level Dependent (BOLD) signal in a network including the amygdala, anterior cingulate cortex, and orbitofrontal cortex | Completed on Day 6 | 
| 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 | Completed on Day 6 | 
| Reward sensitivity | Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT) | Completed on Day 7 | 
| 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 | Completed on Day 7 | 
| Vigilance to fearful and happy faces on the Facial Dot Probe Task (FDOT) | Vigilance derived from reaction time | Completed on Day 7 | 
| 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 | Completed on Day 6 | 
| Relative and global cerebral blood flow | Arterial spin labelling (ASL) global and cerebral blood flow | Completed on Day 6 | 
| 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 | Completed on Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-HT4, Prucalopride, Resolor, Functional Magnetic Resonance Imaging (fMRI), Emotional Processing, Healthy Volunteers