Semaglutide and Cognition in Healthy Volunteers

NCT06363487 | Completed

• 1 other identifier: R87970/RE001
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Cognitive Change

Keywords

Semaglutide; Healthy volunteers; Experimental medicine; Cognition; Reward; Emotional processing; Memory; Energy

Outcome Measures

Primary Outcomes (3)

• 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.

  6-7 days

• 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.

  6-7 days

• Reward (primary)

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

  6-7 days

Secondary Outcomes (5)

• Emotional processing

  6-7 days

• Emotional impulsivity

  6-7 days

• Memory (short- and medium-term) processing

  6-7 days

• Memory (working) processing

  6-7 days

• Energy/activity

  Across 6-7 days

Study Arms (2)

Semaglutide

EXPERIMENTAL

Semaglutide pre-filled pen, 0.5mg in 1.5mL, subcutaneous injection

Drug: Semaglutide, 0.5 mg/mL

Placebo

PLACEBO COMPARATOR

Saline solution 0.9% NaCl, solution for injection 1.5mL, subcutaneous injection syringe

Other: Placebo, 0.9% NaCl 1.5mL

Interventions

Semaglutide, 0.5 mg/mL DRUG

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.

Semaglutide

Placebo, 0.9% NaCl 1.5mL OTHER

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.

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Oxford: lead
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

Related Publications (17)

• Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. 2024 Feb 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK551568/

  PMID: 31855395 BACKGROUND

• 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.

  PMID: 34003475 BACKGROUND

• 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.

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• 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.

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

  BACKGROUND

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MeSH Terms

Interventions

semaglutide

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

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 12, 2024
• Study Start: June 6, 2024
• Primary Completion: December 11, 2024
• Study Completion: December 11, 2024
• Last Updated: June 6, 2025

Record last verified: 2024-04

Locations

GB (1)