PROMOTE: Effects of 5-HT4 Agonism on Cognition and Sleep in Peopl With Low Mood

Cognitive symptoms are common in depression and can persist even when other symptoms of depression have improved. These difficulties can include impairments in memory, attention and executive function, and there remains a need for treatments that specifically target cognitive dysfunction associated with depression. Evidence from preclinical and human experimental studies suggests that activation of the serotonin 4 receptor (5-HT4R) may represent a potential therapeutic approach for targeting cognitive symptoms in depression. The 5-HT4R is expressed in brain regions involved in learning and memory, and experimental studies have investigated whether selective activation of this receptor can influence cognitive processes relevant to depression. Prucalopride is a selective 5-HT4R agonist. In previous human experimental studies, we have found evidence that prucalopride can influence cognitive processes, including learning and memory, in healthy volunteers and people who have recovered from depression. The present study extends this work by investigating the cognitive effects of prucalopride in people who are currently experiencing low mood. The study will use an experimental medicine approach to examine the effects of 5-HT4R activation on cognitive processes relevant to depression. In addition, the study will investigate the effect of prucalopride on sleep architecture. Sleep will be assessed in the home environment using wearable chest patches capable of sleep staging. The study will provide proof-of-concept evidence regarding the effects of 5-HT4R activation on cognition and sleep in people experiencing low mood. These data will inform the design and feasibility of a future randomised controlled trial evaluating prucalopride in people with depression and cognitive impairment.