Effects of Seven Day Prucalopride Administration in Healthy Volunteers

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

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 Overview

• Status: Completed
• Conditions: Mental Disorders; Depressive Disorder; Depression; Mood Disorders; Molecular Mechanisms of Pharmacological Action; Cognition; Antidepressive Agents
• Intervention / Treatment: Drug: Prucalopride; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX3 7JX
    • University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Lactose placebo capsule, once daily for seven days
Experimental: Prucalopride	Drug: Prucalopride; 1mg prucalopride capsule, once daily for seven days; Other Names: Resolor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Susannah E Murphy, DPhil, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2018
• Primary Completion (Actual): May 17, 2019
• Study Completion (Actual): May 17, 2019

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: June 27, 2018
• First Posted (Actual): June 28, 2018

Study Record Updates

• Last Update Posted (Actual): November 18, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Functional Magnetic Resonance Imaging (fMRI); Emotional Processing; Prucalopride; Resolor; 5-HT4
• Additional Relevant MeSH Terms: Pathologic Processes; Depressive Disorder; Disease; Mental Disorders; Mood Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Serotonin Agents; Serotonin Receptor Agonists; Laxatives; Serotonin 5-HT4 Receptor Agonists; Prucalopride
• Other Study ID Numbers: Pruc_7d

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No