Treatment Resistant DepressionGEMSNCT05809609
Glutamate Emotion Memory Study
A study testing Ketamine Hydrochloride in people with Treatment Resistant Depression and Depression, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Clinical depression often includes a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Treatment Resistant Depression, Depression, Major Depressive Disorder
- What is being tested?
- Ketamine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2022to 28 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 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Willing and able to give informed consent for participation in the study
- Sufficiently fluent English to understand and complete the tasks
- Registered with a GP and consents to GP being informed of participation in the study
- Participants need to meet a number of concurrent clinical criteria:
- Current criteria for Major Depressive Disorder, in a current major depressive episode as determined by the SCID-5.
- Inadequate response to at least one and no more than three antidepressant treatments.
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- Currently taking a licensed antidepressant at a therapeutic dose for at least four weeks.
- Pre-menopausal women and male participants engaging in sex with a risk of pregnancy must agree to use a highly effective method of contraception from Screening Visit until 30 days after receiving the study medication treatment.
- Acceptable methods of contraception include:
- Condoms
- Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation oral, injectable or implantable
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomy (or vasectomised partner)
- Sexual abstinence. [Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), and spermicides only are not acceptable methods of contraception.]
- Male participants must not donate sperm until 30 days after receiving the study medication.
- Participants taking non-prescription/prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety
- Willingness to refrain from driving, cycling, or operating heavy machinery, until the following morning or a restful sleep has occurred, whichever is later.
- Willingness to refrain from drinking alcohol for 3 days before the infusion visit and one day before any of the other visits throughout the study.
Who cannot join
- The participant may not enter the study if ANY of the following apply:
- History of /or current DSM-5 bipolar disorder, schizophrenia or emotionally unstable personality disorder [co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed]
- Participants who fulfil current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality
- Diagnosis of a major cognitive disorder or evidence of cognitive impairment
- Clinically significant risk of suicide
- Participants undergoing or who have undergone electroconvulsive therapy for the treatment of the current episode of depression
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- Substance or alcohol use disorder over the past 6 months
- Regular alcohol consumption of more than 21 units a week or excessive alcohol consumption up to three days before any of the in-person study visits or inability to abstain from alcohol for more than 3 days
- Moderate cigarette use (> 10 cigarettes per day)
- History of, or current general medical conditions that in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study
- Current pregnancy (as determined by urine pregnancy test), breastfeeding, planning a pregnancy, or unwillingness to practice birth control during the course of the study
- Clinically significant abnormalities of laboratory tests, physical examination, or ECG. A participant with a clinical abnormality or parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
- Current or past history of heart rhythm disorders
- Clinically significant untreated hypertension
- Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more
- Previous participation in a study using the same, or similar, emotional processing tasks in the last three months
- Previous lifetime use of ketamine or phencyclidine
- Participant with planned medical treatment within the study period that might interfere with the study procedures
- Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Department of Psychiatry, University of Oxford
Oxford
Catherine J Harmer, DPhil, +44 (0)1865 618326, catherine.harmer@psych.ox.ac.uk
About this study
Official title: Does Modulation of Glutamate Transmission in the Brain Using a Sub-anaesthetic Dose of Ketamine Affect Autobiographical Memory, Emotional Processing and Decision-making in Treatment-resistant Depression?
Clinical depression often includes a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. A licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the brain, and has been used as a treatment particularly for depression which hasn't got better with other types of medication. Glutamate plays a role in learning and memory so the investigators are interested in understanding how ketamine can affect how people with depression remember past negative and positive memories and how they experience reward.
The investigators are conducting a study in depressed participants who did not improve with the standard antidepressant treatment to expand our understanding on how ketamine can influence memory, the way people understand emotions and learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks before and after the administration of the study drug, and an MRI scan after administration of the drug. MRI is a type of brain scan that allows us to see how the brain responds during for example memories of things which have happened in the past. This project will help us understand how NMDA antagonists may work in depression.
Read the detailed description
Questions regarding the exact molecular mechanisms of ketamine and its effects on the brain circuitry and networks for the treatment of clinical depression remain largely unanswered. Thus, in the present study the investigators aim to elucidate the effect of ketamine on 1) reconsolidation of autobiographical memories, 2) connectivity of brain circuits involved in autobiographical memories, 3) measures of emotional processing, reward processing and emotional memory in patients suffering from treatment resistant depression. The ultimate goal of this project is to elucidate the antidepressant mechanisms of action of ketamine to facilitate the development of rapid acting antidepressants targeting the glutamatergic system.
- Being tested
- Ketamine Hydrochloride, No intervention (placebo)
- Keywords
- Ketamine, Memory, Mental Health, Learning
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression, Depressive Disorder, Major, Psychological Well-Being
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine HydrochlorideDrug
Ketamine is a high trapping NMDA receptor antagonist which has rapid and reliable antidepressant effects in patients with major depressive disorder (MDD) who fail to respond to at least two antidepressant trials of adequate dose and duration.
No intervention (placebo)Other
Placebo injection (0.9% sodium chloride)
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants in this arm will receive a single intravenous injection, antidepressant dose of Ketamine hydrochloride (0.5mg/kg) Receives: Drug: Ketamine Hydrochloride |
| Placebo | Placebo comparator | Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride) Receives: Other: No intervention (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in magnitude of negative and positive valence adjectives in the autobiographical memory task using a self-reported questionnaire.
To investigate the effects of ketamine on:
- negative emotional bias associated with autobiographical memories in TRD patients.
Each negative (guilty/ashamed, depressed/sad, angry/frustrated, upset, anxious/worried, worthless) and positive (grateful, energetic/motivated, hopeful, confident, loved, happy) valence adjectives. will be rated on a scale from 0 to 100. Change in magnitude will be assessed calculating the difference in ratings of negative and positive adjectives using a self-reported questionnaire from baseline to after treatment
Measured: -1 and 1 days after ketamine/placebo treatment
Brain activation as measured by functional magnetic resonance in a network of areas related to autobiographical memories, including the medial prefrontal cortex and associated networks during the autobiographical memory task.
To investigate the effects of ketamine on:
- on brain circuit associated with autobiographical memories
Measured: 1 days after ketamine/placebo treatment
Secondary outcomes (12)
Accuracy on a computer-based task of facial expression recognition (FERT)
To investigate the effects of ketamine on:
- emotional processing such as emotional recognition.
Measured: -1 day, and up to 2 hours after ketamine/placebo treatment
Reaction time on a computer-based task of facial expression recognition (FERT)
To investigate the effects of ketamine on:
- emotional processing such as emotional recognition.
Measured: -1 day, and up to 2 hours after ketamine/placebo treatment
Accuracy to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)
To investigate the effects of ketamine on:
- emotional processing such as classification of positive and negative descriptor words
Measured: Up to 2 hours after ketamine/placebo treatment
Reaction time to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)
To investigate the effects of ketamine on:
- emotional processing such as classification of positive and negative descriptor words
Measured: Up to 2 hours after ketamine/placebo treatment
Number of positive and negative words correctly recalled (hits) and number of words incorrectly recalled (false alarms) using the Emotional Recall Task (EREC)
To investigate the effects of ketamine on:
- emotional processing such as recall of positive and negative descriptor words
Measured: Up to 2 hours after ketamine/placebo treatment
Accuracy to correctly (hits) and incorrectly (false alarms) recognise positive and negative words using the Emotional Recognition Memory Task (EMEM)
To investigate the effects of ketamine on:
- emotional processing such as recognition of positive and negative descriptor words
Measured: Up to 2 hours after ketamine/placebo treatment
Reaction time to correctly (hits) and incorrectly (false alarms) recognise positive and negative words using the Emotional Recognition Memory Task (EMEM)
To investigate the effects of ketamine on:
- emotional processing such as recognition of positive and negative descriptor words
Measured: Up to 2 hours after ketamine/placebo treatment
Change in response choice during gain and loss using the Probabilistic Instrumental Learning Tasks (PILT)
To investigate the effects of ketamine on:
- reward processing
Measured: 1 day after ketamine/placebo treatment
Brain activation as measured by functional magnetic resonance imaging during the Probabilistic Instrumental Learning Tasks (PILT) in reward-related brain areas, including the ventral striatum and associated networks
To investigate the effects of ketamine on:
- on brain circuit associated with reward processing
Measured: 1 days after ketamine/placebo treatment
Explore performance on information processing and monetary win/loss reinforcement learning (RL) decision-making tasks.
To investigate the effects of ketamine on:
- choice behaviour on win and loss trials
Measured: 1 days after ketamine/placebo treatment
Explore performance on information processing and monetary win/loss reinforcement learning (RL) decision-making tasks using pupillometry
To investigate the effects of ketamine on:
- pupil dilation in context of RL decision making task
Measured: 1 days after ketamine/placebo treatment
Change in choice behaviour (effort and/or reward sensitivity) on accepted offers between session one and two using the Apples Gathering Task (AGT).
To investigate the effects of ketamine on:
- motivation processing
Measured: Up to 2 hours after ketamine/placebo treatment and 7 days after ketamine/placebo treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start1 Jul 2022
- Primary completion28 Nov 2024 (estimated)
- Study completion28 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies 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 will be assigned to receive ketamine or placebo. Ketamine is not being administered for treatment purposes, the purpose is to understand the mechanisms underpinning its effects.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine Harmer, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05809609
- Sponsor's protocol ID
- GEMS
- Acronym
- GEMS
- Status last verified
- May 2024
- First submitted
- 26 Apr 2022
- Last updated
- 21 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Modulation of Glutamate Transmission in the Brain Using a Sub-anaesthetic Dose of Ketamine Affect Autobiographical Memory, Emotional Processing and Decision-making in Treatment-resistant Depression?
- ClinicalTrials.gov ID
- NCT05809609
- Acronym / sponsor ID
- GEMS / GEMS
- Keywords
- Ketamine, Memory, Mental Health, Learning
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 28 Nov 2024 (estimated)
- Study completion
- 28 Dec 2024 (estimated)
- First posted
- 12 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Clinical depression often includes a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. A licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the brain, and has been used as a treatment particularly for depression which hasn't got better with other types of medication. Glutamate plays a role in learning and memory so the investigators are interested in understanding how ketamine can affect how people with depression remember past negative and positive memories and how they experience reward.
The investigators are conducting a study in depressed participants who did not improve with the standard antidepressant treatment to expand our understanding on how ketamine can influence memory, the way people understand emotions and learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks before and after the administration of the study drug, and an MRI scan after administration of the drug. MRI is a type of brain scan that allows us to see how the brain responds during for example memories of things which have happened in the past. This project will help us understand how NMDA antagonists may work in depression.
Detailed description
Questions regarding the exact molecular mechanisms of ketamine and its effects on the brain circuitry and networks for the treatment of clinical depression remain largely unanswered. Thus, in the present study the investigators aim to elucidate the effect of ketamine on 1) reconsolidation of autobiographical memories, 2) connectivity of brain circuits involved in autobiographical memories, 3) measures of emotional processing, reward processing and emotional memory in patients suffering from treatment resistant depression. The ultimate goal of this project is to elucidate the antidepressant mechanisms of action of ketamine to facilitate the development of rapid acting antidepressants targeting the glutamatergic system.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Participants will be assigned to receive ketamine or placebo. Ketamine is not being administered for treatment purposes, the purpose is to understand the mechanisms underpinning its effects.
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamine HydrochlorideParticipants in this arm will receive a single intravenous injection, antidepressant dose of Ketamine hydrochloride (0.5mg/kg) |
| Placebo | Placebo comparator | Other: No intervention (placebo)Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride) |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- Willing and able to give informed consent for participation in the study
- Sufficiently fluent English to understand and complete the tasks
- Registered with a GP and consents to GP being informed of participation in the study
- Current criteria for Major Depressive Disorder, in a current major depressive episode as determined by the SCID-5.
- Inadequate response to at least one and no more than three antidepressant treatments.
Key exclusion criteria (19 listed)
- The participant may not enter the study if ANY of the following apply:
- History of /or current DSM-5 bipolar disorder, schizophrenia or emotionally unstable personality disorder [co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed]
- Participants who fulfil current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality
- Diagnosis of a major cognitive disorder or evidence of cognitive impairment
- Clinically significant risk of suicide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine HydrochlorideKetamine is a high trapping NMDA receptor antagonist which has rapid and reliable antidepressant effects in patients with major depressive disorder (MDD) who fail to respond to at least two antidepressant trials of adequate dose and duration. | Drug | Ketamine |
| No intervention (placebo)Placebo injection (0.9% sodium chloride) | Other | Placebo |
Primary outcome
Change in magnitude of negative and positive valence adjectives in the autobiographical memory task using a self-reported questionnaire.
Time frame: -1 and 1 days after ketamine/placebo treatment
To investigate the effects of ketamine on: - negative emotional bias associated with autobiographical memories in TRD patients. Each negative (guilty/ashamed, depressed/sad, angry/frustrated, upset, anxious/worried, worthless) and positive (grateful, energetic/motivated, hopeful, confident, loved, happy) valence adjectives. will be rated on a scale from 0 to 100. Change in magnitude will be assessed calculating the difference in ratings of negative and positive adjectives using a self-reported questionnaire from baseline to after treatment
Brain activation as measured by functional magnetic resonance in a network of areas related to autobiographical memories, including the medial prefrontal cortex and associated networks during the autobiographical memory task.
Time frame: 1 days after ketamine/placebo treatment
To investigate the effects of ketamine on: - on brain circuit associated with autobiographical memories
12 secondary outcomes
Accuracy on a computer-based task of facial expression recognition (FERT)
Time frame: -1 day, and up to 2 hours after ketamine/placebo treatment
Reaction time on a computer-based task of facial expression recognition (FERT)
Time frame: -1 day, and up to 2 hours after ketamine/placebo treatment
Accuracy to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)
Time frame: Up to 2 hours after ketamine/placebo treatment
Reaction time to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)
Time frame: Up to 2 hours after ketamine/placebo treatment
Number of positive and negative words correctly recalled (hits) and number of words incorrectly recalled (false alarms) using the Emotional Recall Task (EREC)
Time frame: Up to 2 hours after ketamine/placebo treatment
Accuracy to correctly (hits) and incorrectly (false alarms) recognise positive and negative words using the Emotional Recognition Memory Task (EMEM)
Time frame: Up to 2 hours after ketamine/placebo treatment
Reaction time to correctly (hits) and incorrectly (false alarms) recognise positive and negative words using the Emotional Recognition Memory Task (EMEM)
Time frame: Up to 2 hours after ketamine/placebo treatment
Change in response choice during gain and loss using the Probabilistic Instrumental Learning Tasks (PILT)
Time frame: 1 day after ketamine/placebo treatment
Brain activation as measured by functional magnetic resonance imaging during the Probabilistic Instrumental Learning Tasks (PILT) in reward-related brain areas, including the ventral striatum and associated networks
Time frame: 1 days after ketamine/placebo treatment
Explore performance on information processing and monetary win/loss reinforcement learning (RL) decision-making tasks.
Time frame: 1 days after ketamine/placebo treatment
Explore performance on information processing and monetary win/loss reinforcement learning (RL) decision-making tasks using pupillometry
Time frame: 1 days after ketamine/placebo treatment
Change in choice behaviour (effort and/or reward sensitivity) on accepted offers between session one and two using the Apples Gathering Task (AGT).
Time frame: Up to 2 hours after ketamine/placebo treatment and 7 days after ketamine/placebo treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Harmer, DPhil principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketamine Hydrochloride in people with Treatment Resistant Depression and Depression, 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 21 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 21 May 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sara Costi, MD (01865 618303, sara.costi@psych.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in magnitude of negative and positive valence adjectives in the autobiographical memory task using a self-reported questionnaire. (time frame: -1 and 1 days after ketamine/placebo treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 May 2024; AzTrials last refreshed its copy on 29 Oct 2026.