Effects of Seven Day Prucalopride Administration in Healthy Volunteers

Not Applicable

Completed

• Conditions: Depression; Depressive Disorder; Mood Disorders; Molecular Mechanisms of Pharmacological Action; Mental Disorders; Antidepressive Agents; Cognition
• Interventions: Other: Placebo; Drug: Prucalopride

• Registration Number: NCT03572790
• Lead Sponsor: University of Oxford

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-06-07
• Study Start: 2018-06-11
• Study First Submitted QC: 2018-06-27
• Study First Posted: 2018-06-28
• Primary Completion: 2019-05-17
• Study Completion: 2019-05-17
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-14
• Last Update Posted: 2022-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Prucalopride	Prucalopride	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Vigilance to fearful and happy faces on the Facial Dot Probe Task (FDOT)	Completed on Day 7	Vigilance derived from reaction time
Resting state connectivity	Completed on Day 6	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
Neural response to emotional faces	Completed on Day 6	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	Completed on Day 6	BOLD signal to scenes that have previously been seen compared to novel scenes in a network including the hippocampus and parahippocampal regions
Reward sensitivity	Completed on Day 7	Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT)
Categorisation, recall, and recognition of emotional words	Completed on Day 7	Accuracy and reaction time to categorise positive and negative descriptor words; number of words correctly (hits) and incorrectly (false alarms) recalled and recognised
Relative and global cerebral blood flow	Completed on Day 6	Arterial spin labelling (ASL) global and cerebral blood flow
Visual short term memory on the Oxford Memory Test (OMT)	Completed on Day 7	Proportion of correct probe selections, absolute error for probe location, reaction time, and proportion of misbinding errors

Trial Locations

Locations (1)

University of Oxford; 🇬🇧 Oxford, United Kingdom