Effects of Seven Day Prucalopride Administration in Healthy Volunteers

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT03572790

Collaborator

(none)

Enrollment

Location

Arms

11.2

Actual Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Molecular Mechanisms of Pharmacological Action Depression Depressive Disorder Mood Disorders Mental Disorders Antidepressive Agents Cognition	Drug: Prucalopride Other: Placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jun 11, 2018

Actual Primary Completion Date :

May 17, 2019

Actual Study Completion Date :

May 17, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Prucalopride

Drug: Prucalopride

1mg prucalopride capsule, once daily for seven days

Other Names:

Resolor

Placebo Comparator: Placebo

Other: Placebo

Lactose placebo capsule, once daily for seven days

Outcome Measures

Primary Outcome Measures

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

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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)