Semaglutide and Cognition in Healthy Volunteers (OxSENSE)

June 3, 2025 updated by: University of Oxford

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7JX
        • Department of Psychiatry, University of Oxford

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Semaglutide
Semaglutide pre-filled pen, 0.5mg in 1.5mL, subcutaneous injection
Drug: Semaglutide, 0.5 mg/mL
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 Comparator: Placebo
Saline solution 0.9% NaCl, solution for injection 1.5mL, subcutaneous injection syringe
Other: Placebo, 0.9% NaCl 1.5mL
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reward (learning)
Time Frame: 6-7 days
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)
Time Frame: 6-7 days
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)
Time Frame: 6-7 days
Valence on a computer-based task of reward processing (i.e., taste strip task), comparing those receiving drug vs placebo.
6-7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Emotional processing
Time Frame: 6-7 days
Accuracy and reaction times on a computer-based task of emotional processing (i.e., facial expression recognition), comparing those receiving drug vs placebo.
6-7 days
Emotional impulsivity
Time Frame: 6-7 days
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.
6-7 days
Memory (short- and medium-term) processing
Time Frame: 6-7 days
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.
6-7 days
Memory (working) processing
Time Frame: 6-7 days
Accuracy and reaction times on a computer-based task of working memory (N-back), comparing those receiving drug vs placebo.
6-7 days
Energy/activity
Time Frame: Across 6-7 days
Ecological momentary assessment (4 times/day) on 7-point Likert energy/activity scale (very tired to very energetic, very inactive to very active)
Across 6-7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

NIHR Oxford Health Biomedical Research Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2024

Primary Completion (Actual)

December 11, 2024

Study Completion (Actual)

December 11, 2024

Study Registration Dates

First Submitted

April 9, 2024

First Submitted That Met QC Criteria

April 9, 2024

First Posted (Actual)

April 12, 2024

Study Record Updates

Last Update Posted (Actual)

June 6, 2025

Last Update Submitted That Met QC Criteria

June 3, 2025

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R87970/RE001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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