Effects of Seven Day Prucalopride Administration in Healthy Volunteers

University of Oxford50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Molecular Mechanisms of Pharmacological Action Depression

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Recognition of positive and negative facial expressions

Accuracy to recognise positive and negative facial expressions (anger, disgust, fear, happy , sad, surprise)

Time frame: Completed on Day 7

Performance on Auditory Verbal Learning Task (AVLT)

Accuracy on AVLT (number of items recalled across blocks)

Time frame: Completed on Day 7

Secondary Outcomes

Neural response to emotional faces

Blood Oxygen Level Dependent (BOLD) signal in a network including the amygdala, anterior cingulate cortex, and orbitofrontal cortex

Time frame: 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

Time frame: Completed on Day 6

Reward sensitivity

Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT)

Time frame: 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

Time frame: Completed on Day 7

Vigilance to fearful and happy faces on the Facial Dot Probe Task (FDOT)

Vigilance derived from reaction time

Time frame: 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

Time frame: Completed on Day 6

Relative and global cerebral blood flow

Arterial spin labelling (ASL) global and cerebral blood flow

Time frame: 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

Time frame: Completed on Day 7

Effects of Seven Day Prucalopride Administration in Healthy Volunteers

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes