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Cognitive ChangeOxSENSENCT06363487

Semaglutide and Cognition in Healthy Volunteers

A study testing Semaglutide, 0.5 mg/mL in people with Cognitive Change, run by University of Oxford at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA). It is a safe medication approved for use in type-2 diabetes mellitus (T2DM) and obesity. Primarily, it works by counteracting insulin-resistance and inducing weight loss. Read more about this study

Who is it for?
Ages 21 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Cognitive Change
What is being tested?
Semaglutide, 0.5 mg/mL
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
70 participants
Where
1 siteUnited Kingdom
Study dates
6 Jun 2024to 11 Dec 2024
Phase
Interventional
Are there results?
None posted in the registry

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 21 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Male or female
  • Aged from 21 to 55 years
  • Body Mass Index (BMI) from 18 to 30 (because our main outcomes involve cognitive and energy measures, this decision regarding the BMI range has been taken with the purpose of including a more homogeneous sample of healthy participants in terms of baseline cognitive and energy levels)
  • Sufficiently fluent English to understand and complete the tasks
  • Participant is willing and able to give informed consent for participation in the research
  • Not currently taking any regular medications (except the contraceptive pill)

Who cannot join

  • Currently on any regular prescribed medications (except the contraceptive pill), unless unlikely to compromise safety or affect data quality in the opinion of the medical supervisor according to clinical judgement
  • History of, or current significant psychiatric illness in the opinion of the medical supervisor according to clinical judgement
  • Current alcohol or substance misuse disorder (<6 months)
  • Current moderate or severe dyslexia
  • History of, or current significant medical illness in the opinion of the medical supervisor according to clinical judgement
  • History of, or current pancreatitis
Show all 15Show fewer
  • History of, or current severe congestive heart failure, end-stage renal disease, hepatic disease
  • History of, or current significant neurological condition (e.g., epilepsy)
  • History of, or current significant thyroid disorder
  • History (including family history) of, or current multiple endocrine neoplasia syndrome type-2 (MEN 2) or medullary thyroid carcinoma (MTC)
  • Known type-1 or type-2 diabetes mellitus
  • Known hypersensitivity to the study drug (i.e., semaglutide)
  • Pregnant, breast feeding, or person of child-bearing potential not using appropriate contraceptive measures including hormonal contraception, intrauterine device, bilateral tubal occlusion, vasectomised partner, condom, absolute sexual abstinence - periodic sexual abstinence, withdrawal, and spermicides-only are not acceptable methods of contraception
  • Participation in a study that uses the same or similar computer tasks (O-ETB, see below) as those used in the present study
  • Participation in a study that involves the use of a medication within the last 3 months

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Department of Psychiatry, University of Oxford

    Oxford, Oxfordshire, OX3 7JX

Other trials in United Kingdom

About this study

Official title: Effects of Single-dose Semaglutide on Cognition and Energy in Healthy Volunteers

Semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA). It is a safe medication approved for use in type-2 diabetes mellitus (T2DM) and obesity. Primarily, it works by counteracting insulin-resistance and inducing weight loss. It also acts on several other interconnected neurobiological, immunological (esp. inflammatory), endocrine-metabolic, and gut-brain axis processes that play a role in depressive symptoms. Its effects on cognition and energy are currently unknown. In this study we are using semaglutide as an experimental tool to further investigate these relationships.

Read the detailed description

Semaglutide is a novel GLP-1RA licensed for T2DM and obesity, which mainly works by offsetting insulin-resistance and stimulating weight loss (1). It also acts on various neurobiological, immunological, endocrine-metabolic, and gut-brain axis processes that play a role in depressive symptoms (2). Preliminary evidence suggests these drugs are safe from a neuropsychiatric perspective (3) and could be beneficial in unipolar (4) and bipolar depression (5) - an outcome possibly mediated by inflammatory pathways (6).

The proposed study investigates the effects of semaglutide on cognition and energy, which are currently unknown. Work in our laboratory established that short-term use of conventional antidepressants in healthy volunteers shifts reward sensitivity and emotional cognition (7) - an important neuropsychological mechanism of antidepressant action (8). An experimental medicine trial that assesses the effects of semaglutide on reward sensitivity emotional cognition can validate its potential to be repurposed for treating depressive disorders (9). Moreover, brain insulin resistance, likely lessened by semaglutide, is associated with deficit in impulse-control as well as non-emotional cognitive and energy impairment in people with depression (10). Finally, defining the overall cognitive and energy profile of semaglutide is important for the many people already taking it for its licensed indications (i.e., T2DM, obesity).

Therefore, the primary objective of this study is to assess the effect of a single dose of semaglutide 0.5mg subcutaneous injection vs placebo on reward sensitivity tasks in healthy volunteers. Secondary objectives include the investigation of the effects of semaglutide on other cognitive domains (emotional processing, impulsivity, memory) and energy/activity levels. Psychological questionnaires are also measured as relevant covariates.

Being tested
Semaglutide, 0.5 mg/mL, Placebo, 0.9% NaCl 1.5mL
Keywords
Semaglutide, Healthy volunteers, Experimental medicine, Cognition, Reward, Emotional processing, Memory, Energy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Semaglutide, 0.5 mg/mLDrug

    Injected subcutaneously (pre-filled pen) in the upper arm (preferred site), in the abdomen, or in the thigh according to participant's preference. The participant will be asked to wear an eye blindfold during the time of the study medication/placebo administration, to avoid compromising blinding. It is not possible to blind the researcher administering the medication/placebo because semaglutide comes in specific pre-filled pens. The person who administers the subcutaneous injection will be suitably trained and experienced, and have been authorised to do so by the Principal Investigator - they will not be involved in other aspects of the study for that participant to avoid compromising blinding.

  • Placebo, 0.9% NaCl 1.5mLOther

    Injected subcutaneously (subcutaneous injection syringe) in the upper arm (preferred site), in the abdomen, or in the thigh according to participant's preference. The participant will be asked to wear an eye blindfold during the time of the study medication/placebo administration, to avoid compromising blinding. The person who administers the subcutaneous injection will be suitably trained and experienced, and have been authorised to do so by the Principal Investigator - they will not be involved in other aspects of the study for that participant to avoid compromising blinding.

Study groups in NCT06363487
Study groupRoleWhat they receive
SemaglutideExperimentalSemaglutide pre-filled pen, 0.5mg in 1.5mL, subcutaneous injection
Receives: Drug: Semaglutide, 0.5 mg/mL
PlaceboPlacebo comparatorSaline solution 0.9% NaCl, solution for injection 1.5mL, subcutaneous injection syringe
Receives: Other: Placebo, 0.9% NaCl 1.5mL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reward (learning)

    Win/loss and valence on a computer-based task of reward processing (i.e., probabilistic instrumental learning task), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  2. Reward (effort-based)

    Win/loss and valence on a computer-based task of reward processing (i.e., apple-gathering task), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  3. Reward (primary)

    Valence on a computer-based task of reward processing (i.e., taste strip task), comparing those receiving drug vs placebo.

    Measured: 6-7 days

Secondary outcomes (5)

  1. Emotional processing

    Accuracy and reaction times on a computer-based task of emotional processing (i.e., facial expression recognition), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  2. Emotional impulsivity

    Accuracy and reaction times on a computer-based task of emotional response inhibition (i.e., affective go/no-go task), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  3. Memory (short- and medium-term) processing

    Accuracy and reaction times on a computer-based tasks of (short- and medium-term) memory (auditory-verbal learning task), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  4. Memory (working) processing

    Accuracy and reaction times on a computer-based task of working memory (N-back), comparing those receiving drug vs placebo.

    Measured: 6-7 days

  5. Energy/activity

    Ecological momentary assessment (4 times/day) on 7-point Likert energy/activity scale (very tired to very energetic, very inactive to very active)

    Measured: Across 6-7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2024
  2. Study start6 Jun 2024
  3. Primary completion11 Dec 2024
  4. Study completion11 Dec 2024

Resources

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
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06363487
Sponsor's protocol ID
R87970/RE001
Acronym
OxSENSE
Status last verified
Apr 2024
First submitted
9 Apr 2024
Last updated
6 Jun 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Anonymised research data without any personal data (e.g., reaction time data) will also be stored on private Open Science Framework (OSF) project components that are accessible only to the research team. We have previously confirmed with the University's Sponsor (formerly CTRG) in December 2019 that OSF can be used in this way to store anonymised data (with no personal data or linking files). Parts of the data might be uploaded to online data repositories or made publicly available on OSF in a completely anonymised fashion, to facilitate open science. Data uploaded in this way will be stored on OSF indefinitely.

Publications

  • Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. 2024 Feb 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK551568/

    PubMed 31855395

  • Detka J, Glombik K. Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression. Pharmacol Rep. 2021 Aug;73(4):1020-1032. doi: 10.1007/s43440-021-00274-8. Epub 2021 May 18.

    PubMed 34003475

  • O'Neil PM, Aroda VR, Astrup A, Kushner R, Lau DCW, Wadden TA, Brett J, Cancino AP, Wilding JPH; Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials. Diabetes Obes Metab. 2017 Nov;19(11):1529-1536. doi: 10.1111/dom.12963. Epub 2017 Jul 21.

    PubMed 28386912

  • Pozzi M, Mazhar F, Peeters GGAM, Vantaggiato C, Nobile M, Clementi E, Radice S, Carnovale C. A systematic review of the antidepressant effects of glucagon-like peptide 1 (GLP-1) functional agonists: Further link between metabolism and psychopathology: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders. J Affect Disord. 2019 Oct 1;257:S0165-0327(19)30593-2. doi: 10.1016/j.jad.2019.05.044. Epub 2019 May 28.

    PubMed 31153593

  • Mansur RB, Ahmed J, Cha DS, Woldeyohannes HO, Subramaniapillai M, Lovshin J, Lee JG, Lee JH, Brietzke E, Reininghaus EZ, Sim K, Vinberg M, Rasgon N, Hajek T, McIntyre RS. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: A pilot, open-label study. J Affect Disord. 2017 Jan 1;207:114-120. doi: 10.1016/j.jad.2016.09.056. Epub 2016 Oct 1.

    PubMed 27721184

  • Moulton CD, Pickup JC, Amiel SA, Winkley K, Ismail K. Investigating incretin-based therapies as a novel treatment for depression in type 2 diabetes: Findings from the South London Diabetes (SOUL-D) Study. Prim Care Diabetes. 2016 Apr;10(2):156-9. doi: 10.1016/j.pcd.2015.06.003. Epub 2015 Jun 29.

    PubMed 26137918

  • Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004 Jul;161(7):1256-63. doi: 10.1176/appi.ajp.161.7.1256.

    PubMed 15229059

  • Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017 May;4(5):409-418. doi: 10.1016/S2215-0366(17)30015-9. Epub 2017 Jan 31.

    PubMed 28153641

  • Godlewska BR, Harmer CJ. Cognitive neuropsychological theory of antidepressant action: a modern-day approach to depression and its treatment. Psychopharmacology (Berl). 2021 May;238(5):1265-1278. doi: 10.1007/s00213-019-05448-0. Epub 2020 Jan 15.

    PubMed 31938879

  • Hamer JA, Testani D, Mansur RB, Lee Y, Subramaniapillai M, McIntyre RS. Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression. Exp Neurol. 2019 May;315:1-8. doi: 10.1016/j.expneurol.2019.01.016. Epub 2019 Jan 26.

    PubMed 30695707

  • Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature. 2006 Aug 31;442(7106):1042-5. doi: 10.1038/nature05051. Epub 2006 Aug 23.

    PubMed 16929307

  • Bonnelle V, Veromann KR, Burnett Heyes S, Lo Sterzo E, Manohar S, Husain M. Characterization of reward and effort mechanisms in apathy. J Physiol Paris. 2015 Feb-Jun;109(1-3):16-26. doi: 10.1016/j.jphysparis.2014.04.002. Epub 2014 Apr 18.

    PubMed 24747776

  • Amsterdam JD, Settle RG, Doty RL, Abelman E, Winokur A. Taste and smell perception in depression. Biol Psychiatry. 1987 Dec;22(12):1481-5. doi: 10.1016/0006-3223(87)90108-9. No abstract available.

    PubMed 3676376

  • Harmer CJ, O'Sullivan U, Favaron E, Massey-Chase R, Ayres R, Reinecke A, Goodwin GM, Cowen PJ. Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatry. 2009 Oct;166(10):1178-84. doi: 10.1176/appi.ajp.2009.09020149. Epub 2009 Sep 15.

    PubMed 19755572

  • Colwell, M. J., Murphy, S., & Harmer, C. J. (2022). Emotional Go/No-Go Task (Oxford) (Psychopy). Zenodo. https://doi.org/10.5281/zenodo.6207865

Questions about this trial

What is this clinical trial studying?

A study testing Semaglutide, 0.5 mg/mL in people with Cognitive Change, run by University of Oxford at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reward (learning) (time frame: 6-7 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06363487, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2025.

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