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

Summary

Serotonin is a chemical in the brain that plays an important role in mood, sleep, and other functions. It works by attaching to different types of serotonin receptors on brain cells. These receptors act like "locks", with serotonin acting like a "key". Different types of serotonin receptors have different effects in the brain. Prucalopride is a licensed medication used to treat constipation. It acts on a particular serotonin receptor, called the serotonin 4 receptor. Researchers are interested in this receptor because understanding how it works in the brain may help us learn more about depression and could contribute to the development of new treatments in the future. The purpose of this study is to investigate the effects of prucalopride in people experiencing low mood. We will compare prucalopride with a placebo (a treatment with no active medication) to find out whether activating the serotonin 4 receptor affects sleep and aspects of thinking, including memory, attention and decision making.

Timeline

Start

2026-10

Primary completion

2028-07

Completion

2028-07

Publications

• Background De Giorgi R, Waters S, Gillespie AL, Quinton AMG, Colwell MJ, Murphy SE, Cowen PJ, Harmer CJ. Effects of 28-day simvastatin administration on emotional processing, reward learning, working memory, and salivary cortisol in healthy participants at-risk for depression: OxSTEP, an online experimental medicine trial. Psychol Med. 2025 May 22;55:e155. doi: 10.1017/S0033291725001187.
• Background Colwell MJ, Tagomori H, Chapman S, Gillespie AL, Cowen PJ, Harmer CJ, Murphy SE. Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research. Transl Psychiatry. 2022 Nov 17;12(1):484. doi: 10.1038/s41398-022-02249-6.
• Background Ahern E, White J, Slattery E. Change in Cognitive Function over the Course of Major Depressive Disorder: A Systematic Review and Meta-analysis. Neuropsychol Rev. 2025 Mar;35(1):1-34. doi: 10.1007/s11065-023-09629-9. Epub 2024 Feb 5.
• Background de Cates AN, Harmer CJ, Harrison PJ, Cowen PJ, Emmanuel A, Travis S, Murphy SE, Taquet M. Association between a selective 5-HT4 receptor agonist and incidence of major depressive disorder: emulated target trial. Br J Psychiatry. 2024 Sep;225(3):371-378. doi: 10.1192/bjp.2024.97.
• Background Singh S, Strong R, Xu I, Fonseca LM, Hawks Z, Grinspoon E, Jung L, Li F, Weinstock RS, Sliwinski MJ, Chaytor NS, Germine LT. Ecological Momentary Assessment of Cognition in Clinical and Community Samples: Reliability and Validity Study. J Med Internet Res. 2023 Jun 2;25:e45028. doi: 10.2196/45028.
• Background de Cates AN, Wright LC, Martens MAG, Gibson D, Turkmen C, Filippini N, Cowen PJ, Harmer CJ, Murphy SE. Deja-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task. Transl Psychiatry. 2021 Oct 4;11(1):497. doi: 10.1038/s41398-021-01568-4.
• Background Murphy SE, Wright LC, Browning M, Cowen PJ, Harmer CJ. A role for 5-HT4 receptors in human learning and memory. Psychol Med. 2020 Dec;50(16):2722-2730. doi: 10.1017/S0033291719002836. Epub 2019 Oct 16.
• Background Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, Harmer CJ. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med. 2021 May;51(7):1111-1120. doi: 10.1017/S0033291720000604. Epub 2020 Apr 3.
• Background Conradi HJ, Ormel J, de Jonge P. Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study. Psychol Med. 2011 Jun;41(6):1165-74. doi: 10.1017/S0033291710001911. Epub 2010 Oct 8.

Drugs

Indications