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

NCT07848477 | Not Yet Recruiting

• 1 other identifier: PROMOTE (2544373)
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Low Mood; Depression - Major Depressive Disorder

Keywords

Low Mood; Cognition; Sleep; Depression; prucalopride; 5-HT4 receptor; cognitive function

Outcome Measures

Primary Outcomes (1)

• Auditory Verbal Learning Test (AVLT)

  Verbal learning and memory will be assessed using the Auditory Verbal Learning Test, including measures of immediate recall, delayed recall, and recognition memory. AVLT performance will be compared between prucalopride and placebo groups following the intervention.

  Day 14 (post-intervention)

Secondary Outcomes (12)

• Sleep outcomes measured using wearable sleep monitoring

  Baseline (Day 0) and Days 1-4 of the intervention

• Digit Span Task

  Baseline and Day 14 (post-intervention)

• Emotional Go/No-Go (EGNG)

  Day 14 (post-intervention)

• Probabilistic Reversal Learning Task (PRL)

  Day 14 (post-intervention)

• Mnemonic Similarity Task (MST)

  Day 14 (post-intervention)

Other Outcomes (6)

• State Subjective Cognition Scale (SSCS)

  Baseline and daily during the 14-day intervention.

• Positive and Negative Affect Schedule (PANAS)

  Baseline and daily during the 14-day intervention.

• Patient Health Questionnaire-9 (PHQ-9)

  Baseline, Day 7 and Day 14 of the intervention

Study Arms (2)

Prucalopride

EXPERIMENTAL

Participants will receive daily oral prucalopride for 14 days.

Drug: Prucalopride

Placebo

PLACEBO COMPARATOR

Participants will receive daily oral placebo for 14 days.

Drug: Placebo Comparator

Interventions

Prucalopride DRUG

Prucalopride will be administered orally once daily for 14 days. Participants will receive 1 mg once daily on Days 1-2 and 2 mg once daily on Days 3-14.

Prucalopride

Placebo Comparator DRUG

A matching placebo (lactose) will be administered orally once daily for 14 days. Participants will take one placebo capsule on Days 1-2 and two placebo capsules on Days 3-14, matching the dosing schedule of the prucalopride intervention.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18-65
• Male or female
• Participant is willing and able to give informed consent for participation in the research
• Body mass index in the range of 18-35 inclusive
• Current PHQ-9 score in the range of 9-15

You may not qualify if:

• Any current or previous episode of a severe mental illness, other than Depressive Disorder. Comorbid Anxiety disorders will be allowed, but not OCD or PTSD.
• A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia
• Body Mass Index outside the range of 18 to 35 inclusive
• Any significant current medical condition likely to interfere with conduct of the study or analysis of data
• Ongoing psychopharmacological treatment for depression, including hypnotics (psychotherapy will be allowed as long as not newly-started in the last 6 weeks)
• High consumption of illicit substances to an extent that would make complying with study protocol challenging (including alcohol, caffeine, nicotine)
• Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study
• Currently pregnant, trying to get pregnant, or breast feeding
• Current, or a significant history of, gastro-intestinal disorder or irritable bowel syndrome
• Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose
• Participation in a study that involves the use of a medication or novel vaccine within the last three months
• Participation in a study using the same tasks in the last year
• Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging, including yellow/blue colourblindness
• A head injury causing concussion or loss of consciousness within the last six months
• Moderate to high risk of suicide or self-harm

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Warneford Hospital

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Related Publications (9)

• 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.

  PMID: 40400441 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.

  PMID: 36396622 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.

  PMID: 38315296 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.

  PMID: 39109752 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.

  PMID: 37266996 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.

  PMID: 34602607 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.

  PMID: 31615585 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.

  PMID: 32241310 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.

  PMID: 20932356 BACKGROUND

MeSH Terms

Conditions

Consciousness Disorders; Depression

Interventions

prucalopride

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Susannah E Murphy, DPhil

  Department of Psychiatry, University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susannah Murphy, PhD

CONTACT

+441865618313; susannah.murphy@psych.ox.ac.uk

Finley T Watton, MBiomedSci Neurosciences

CONTACT

+447593941882; finley.watton@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants randomised to a active medication group (n=30) or placebo group (n=30)

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: September 30, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Available following the publication of the study results
• Access Criteria: Available to researchers on request, subject to approal by the study team/institution and applicable ethical and data protection requirements

Locations

GB (1)