Low MoodPROMOTENCT07848477
PROMOTE: Effects of 5-HT4 Agonism on Cognition and Sleep in Peopl With Low Mood
A study testing Prucalopride in people with Low Mood and Depression - Major Depressive Disorder, run by University of Oxford at 1 site in United Kingdom.
Trial 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". Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Low Mood, Depression - Major Depressive Disorder
- What is being tested?
- Prucalopride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2026to Jul 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
- Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion)
- Ongoing psychopharmacological treatment for depression, including hypnotics (psychotherapy will be allowed as long as not newly-started in the last 6 weeks)
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- 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
- Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Chief Investigator.
- Additional Exclusion Criteria for Participants in the Sleep Study Cohort:
- Unable to undergo cardiac monitoring
- Unable to wear the sleep patch device for full monitoring period
- Implanted neurostimulator or pacemaker
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
Warneford Hospital
Oxford, Oxfordshire, OX3 7JX
Susannah Murphy, PhD, +441865618313, susannah.murphy@psych.ox.ac.uk
Susannah E Murphy, DPhil
About this study
Official title: Investigating the Effect of 5-HT4 Receptor Agonism on Cognition and Sleep in People With Low Mood
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.
Read the detailed description
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.
- Conditions
- Low Mood, Depression - Major Depressive Disorder
- Being tested
- Prucalopride, Placebo Comparator
- Keywords
- Low Mood, Cognition, Sleep, Depression, prucalopride, 5-HT4 receptor, cognitive function
- Medical subject headings
- Consciousness Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrucaloprideDrug
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.
Placebo ComparatorDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Prucalopride | Experimental | Participants will receive daily oral prucalopride for 14 days. Receives: Drug: Prucalopride |
| Placebo | Placebo comparator | Participants will receive daily oral placebo for 14 days. Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 14 (post-intervention)
Secondary outcomes (12)
Sleep outcomes measured using wearable sleep monitoring
Sleep will be assessed using a wearable chest patch in a subset of participants (n=20 total, 10 per intervention group). Measures will include sleep duration, sleep quality and sleep staging. Sleep outcomes will be compared between the prucalopride and placebo groups.
Measured: Baseline (Day 0) and Days 1-4 of the intervention
Digit Span Task
Maximum digit span will be assessed as a measure of working memory and compared between the prucalopride and placebo groups
Measured: Baseline and Day 14 (post-intervention)
Emotional Go/No-Go (EGNG)
Inhibitory control will be assessed using the EGNG task, including measures of commission errors, omission errors, and reaction time. Performance will be compared between prucalopride and placebo groups follwing the intervention.
Measured: Day 14 (post-intervention)
Probabilistic Reversal Learning Task (PRL)
Cognitive flexibility and reward-based learning will be assessed using the PRL task, including measures such as response accuracy, reversal errors, and sensitivity to reward and punishment. Performance will be compared between prucalopride and placebo groups following the intervention.
Measured: Day 14 (post-intervention)
Mnemonic Similarity Task (MST)
Pattern separation and recognition memory will be assessed using the MST. Performance will be compared between the prucalopride and placebo groups following the intervention.
Measured: Day 14 (post-intervention)
Serial Addition Task (SAT)
Working memory will be assessed using the SAT. Performance will be compared between the prucalopride and placebo groups following the intervention
Measured: Day 14 (post-intervention)
Matrix Span Task
Visual working memory assessed using the Matrix Span Task, administered remotely via the NeuroUX app. Performance (accuracy/reaction time) will be compared between prucalopride and placebo groups.
Measured: Baseline and Days 2, 3, 5, 6, 8, 10, 11 and 13 of the 14-day intervention.
Variable Difficulty List Memory Test (VDLMT)
Verbal learning and recognition memory will be assessed using the VDLMT, administered remotely via the NeuroUX app. Performance will be compared between the prucalopride and placebo groups.
Measured: Baseline and Days 1, 2, 4, 6, 7, 9, 11, 12 and 14 of the 14-day intervention.
N-Back Test
Working memory will be assessed using the 2-back version of the N-back task, administered remotely via the NeuroUX app. Performance will be compared between the prucalopride and placebo groups.
Measured: Baseline and Days 1, 3, 4, 6, 8, 9, 11, 13 and 14 of the 14-day intervention.
Digit Symbol Substitution Task (DSST)
Processing speed will be assessed using the DSST, administered remotely via the NeuroUX app. Performance will be compared between the prucalopride and placebo groups.
Measured: Baseline and Days 1, 3, 5, 7, 8, 10, 12 and 13 of the 14-day intervention.
Quick Tap 2 Test
Response inhibition will be assessed using the Quick Tap 2 test, a go/no-go task administered remotely via the NeuroUX app. Performance will be compared between the prucalopride and placebo groups.
Measured: Baseline and Days 2, 4, 5, 7, 9, 10, 12 and 14 of the 14-day intervention.
Paired Associates Learning (PAL)
Verbal associative and episodic memory will be assessed using the PAL task. Performance will be compared between the prucalopride and placebo groups.
Measured: Day 14 (post-intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2026
- Study startOct 2026 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Low MoodStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants randomised to a active medication group (n=30) or placebo group (n=30)
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susannah E Murphy, DPhil, Principal investigator, Department of Psychiatry, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07848477
- Sponsor's protocol ID
- PROMOTE (2544373)
- Acronym
- PROMOTE
- Status last verified
- Sep 2026
- First submitted
- 23 Sep 2026
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised individual participant data (IPD) that underlie the results reported in publications arising from this study will be available to researchers upon request, subject to appropriate ethical, data protection and institutional requirements
Publications
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.
PubMed 40400441Colwell 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.
PubMed 36396622Ahern 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.
PubMed 38315296de 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.
PubMed 39109752Singh 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.
PubMed 37266996de 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.
PubMed 34602607Murphy 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.
PubMed 31615585Murphy 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.
PubMed 32241310Conradi 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.
PubMed 20932356