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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prucalopride | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prucalopride | Drug | 1mg prucalopride capsule, once daily for seven days |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susannah E Murphy, DPhil | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Oxford | Oxford | OX3 7JX | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37098409 | Derived | de Cates AN, Martens MAG, Wright LC, Gibson D, Spitz G, Gould van Praag CD, Suri S, Cowen PJ, Murphy SE, Harmer CJ. 5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action. Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Nov;8(11):1124-1134. doi: 10.1016/j.bpsc.2023.03.014. Epub 2023 Apr 23. |
| Label | URL |
|---|---|
| Psychopharmacology and Emotion Research Laboratory | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 16, 2019 | Aug 13, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 28, 2022 | Nov 8, 2022 | SAP_004.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 5, 2018 | Aug 13, 2019 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| C406662 | prucalopride |
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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.
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| Placebo | Other | Lactose placebo capsule, once daily for seven days |
|
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 |