Effects of Acute Prucalopride Administration in Healthy Volunteers

Study Overview
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Brief Summary
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This study will investigate whether administration of a single dose of the serotonin receptor subtype 4 (5-HT4) partial agonist prucalopride has effects on emotional processing and non-emotional cognition 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 a single dose of either prucalopride (1mg) or placebo. All participants will come for a Screening Visit to ensure their suitability for the study. If they meet study criteria, they will be invited to a Research Visit, where they will receive the study medication and wait for two hours while the drug reaches peak levels. After two hours they will be asked to complete a series of computer-based tasks measuring emotional, non-emotional cognitive processing, and reward processing. The primary study hypothesis is that acute prucalopride administration will have positive effects on processing facial expressions of emotion. Secondary hypotheses are that acute prucalopride administration will affect other measures of emotional processing, and non-emotional cognition.

Official Title
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The Effect of a Single Dose of Prucalopride on Emotional Processing in Healthy Volunteers

Conditions
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Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder, Mood Disorders, Mental Disorder, 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: Male or female Aged 18-40 years Willing and able to give informed consent for participation in the study Sufficiently fluent English to understand and complete the task Exclusion Criteria: Current usage of psychoactive medication (except the contraceptive pill, the Depo-Provera injection or the progesterone implant) Any past or current Axis 1 DSM-IV psychiatric disorder Significant medical condition Current or past gastro-intestinal disorder or irritable bowel syndrome Current pregnancy or breastfeeding Known lactate deficiency or any other problem absorbing lactose, galactose or glucose Current or past history of drug or alcohol dependency Participation in a psychological or medical study involving the use of medication within the last 3 months Previous participation in a study using the same, or similar, emotional processing tasks Smoker > 5 cigarettes per day Typically drinks > 6 caffeinated drinks per day

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 of the drug. Participants in the placebo group will receive a lactose placebo. 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>1mg prucalopride capsule | Drug: Prucalopride<br>* 1mg prucalopride tablet, encapsulated in white capsule<br>* Other names: Resolor;|
| Placebo Comparator: Placebo<br>Lactose placebo capsule | Other: Placebo<br>* Lactose placebo tablet, encapsulated in white capsule<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 identify positive vs. negative facial expressions of emotion on the FERT | Day 1: 2-5 hours post drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recall of emotional words | Number of positive and negative words correctly (and incorrectly) recalled in the EREC task | Day 1: 2-5 hours post drug administration | 
| Recognition of emotional words | Number of positive and negative words correctly (and incorrectly) recognised in the EMEM task | Day 1: 2-5 hours post drug administration | 
| Attentional vigilance to emotional faces | Attentional vigilance to fearful and happy faces in the FDOT task | Day 1: 2-5 hours post drug administration | 
| Recall of words Auditory Verbal Learning Task (AVLT) | Number of items correctly and incorrectly recalled across blocks | Day 1: 2-5 hours post drug administration | 
| Reward and loss sensitivity | Proportion of participants on each trial that chose the correct (high probability) symbol in the win condition, and the incorrect (high probability) symbol in the loss condition of the PILT task | Day 1: 2-5 hours post drug administration | 
| Working memory performance | Mean accuracy and reaction time on 1-back, 2-back and 3-back conditions compared with 0-back condition on the N-back task | Day 1: 2-5 hours post drug administration | 
| Contextual learning | Difference between reaction time and accuracy on novel and repeated arrays in the contextual cueing task | Day 1: 2-5 hours post drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-HT4, Prucalopride, Resolor, Emotional Processing, Healthy Volunteers