DepressionRELAKSNCT04850911
Reward Emotion Learning and Ketamine Study
A study testing Ketamine Hydrochloride in people with Depression and Major Depressive Disorder, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression, Major Depressive Disorder, Treatment Resistant Depression
- 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
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Aug 2021to May 2023
- 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 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI between 18 and 30
- Participant is willing and able to give informed consent for participation in the study
- Sufficient knowledge of English language to understand and complete study tasks
- 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 signing legal documents within 7 days after the infusion visit.
- 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
- Any current or past DSM-V significant psychiatric disorder including any psychotic, mood and anxiety and borderline personality disorders
- History of, or current medical conditions which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions
- First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
- History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
- Current or past history of heart rhythm disorders
- Clinically significant hypertension
Show all 24Show fewer
- Increased intraocular pressure/glaucoma
- Current pregnancy (as determined by urine pregnancy test taken during Screening and Infusion Visits) or breastfeeding
- Clinically significant abnormal values for clinical chemistry (e.g. liver function tests), urine drug screen, blood pressure measurement and 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 previous intake (last three months) of any medication that has a significant potential to affect mental functioning (e.g. benzodiazepines, antidepressants, neuroleptics etc.)
- Any intake of recreational drugs in the last 3 months (e.g. marijuana, ecstasy etc.)
- Lifetime recreational use of ketamine or phencyclidine
- Regular alcohol consumption of more than 14 units a week or excessive alcohol consumption up to three days before any of the in-person study visits
- Inability to abstain from alcohol for more than 1 week
- Regular smoker (> 5 cigarettes per day)
- Excessive caffeine user (> 6 caffeinated drinks per day)
- History of recurrent rashes or history of allergic reactions to relevant substances (ketamine treatment, placebo treatment)
- Previous participation in a study using the same or similar tasks
- Current participation in another study or participation in similar study within the last 6 months
- Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator
- Claustrophobia
- Any implants (including dental implants) or pacemaker
- Tattoos above the chest
- Any other MRI contraindications outlined in FMRIB 7 Tesla scanning safety form
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
University of Oxford
Oxford, OX3 7JZ
About this study
Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. In this study the investigators will further explore the effects of ketamine on learning and memory as well as measuring the associated changes at neural level in a sample of healthy volunteers. Participants will be assigned to receive ketamine or placebo and complete a set of tasks which will allow the investigators to quantify the effect of ketamine on learning about reward and punishment and memory for learned reward associations 24 hours after ketamine infusion. This study will help the investigators to understand the basis of ketamine's antidepressant effects and aid the development of new treatments for depression.
- Being tested
- Ketamine Hydrochloride, No intervention (placebo)
- Keywords
- Ketamine, Learning, Memory, Habenula
- Medical subject headings
- Depression, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
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 have failed to respond to conventional monoaminergic agents.
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, 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.
Activation of the habenula during the Pavlovian conditioning task in response to the conditioned stimulus associated with pain stimuli and in response to the receipt of shock.
Blood Oxygen Level Dependent (BOLD) signal in the habenula at the time of the shock-associated conditioned stimulus presentation and at the time of shock delivery.
Measured: 24 hours after ketamine infusion
Habenula response to the absence of expected reward and the receipt of an unexpected loss (i.e. a negative prediction error signal) in both the reward maximisation and loss minimisation tasks.
BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Measured: 24 hours after ketamine administration
Preference for high-reward probability shapes learned after winning money (in the Wheel of Fortune draw) during the preference test.
Proportion of choices where high-reward probability shapes are selected. This will be based on the difference between the perceived reward probability of shapes learned after the winning and losing of money (an area under the curve measure).
Measured: +/- 24 hours after ketamine administration
Secondary outcomes (13)
Ventral striatum response to the expected reward and the omission an unexpected loss (i.e. a positive prediction error signal) in both the reward maximisation and loss minimisation tasks.
BOLD signal in the ventral striatum at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Measured: 24 hours after ketamine administration
Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test.
Baseline corrected pupil dilation measured at the time of option presentation during each choice trial of the affective memory preference test.
Measured: 24 hours after ketamine administration
Difference in pupil response to shapes learned after winning versus losing money.
Between groups comparison of pupil dilation in response to shapes learned after a loss and shapes learned after a win in Wheel of Fortune draw that induces experimental change in negative/positive affect.
Measured: 24 hours after ketamine administration
Amount of money earned in the learning and memory task.
Between groups comparison of the total amount of money earned during the learning and memory task.
Measured: Final component completed 24 hours after ketamine administration before scanning
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of salivary cortisol in response to Oxford Cognition Stress Task.
Measured: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of salivary alpha amylase in response to Oxford Cognition Stress Task.
Measured: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of heart rate in response to Oxford Cognition Stress Task.
Measured: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task.
Measured: 1-week after ketamine infusion
Recognition of positive and negative facial expressions.
Recognition accuracy for positive and negative facial expressions
Measured: Immediately and 24 hours after ketamine infusion
Recognition of positive and negative facial expressions.
Reaction time to recognise positive and negative facial expressions
Measured: Immediately and 24 hours after ketamine infusion
Categorisation of emotional words.
Accuracy of categorisation for positive and negative descriptor words.
Measured: 24 hours after ketamine infusion
Recognition of emotional words.
Reaction time to categorise positive and negative descriptor words.
Measured: 24 hours after ketamine infusion
Recall of emotional words.
Number of words correctly (hits) and incorrectly (false alarms) recalled.
Measured: 24 hours after ketamine infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2021
- Study start25 Aug 2021
- Primary completionMay 2023 (estimated)
- Study completionMay 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 either 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
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Responsible party
- Principal investigator, Catherine Harmer, University of Oxford
- Investigators
- Catherine Harmer, PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04850911
- Sponsor's protocol ID
- RELAKS_HV
- Acronym
- RELAKS
- Status last verified
- Mar 2023
- First submitted
- 1 Apr 2021
- Last updated
- 28 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reward Emotion Learning and Ketamine Study
- ClinicalTrials.gov ID
- NCT04850911
- Acronym / sponsor ID
- RELAKS / RELAKS_HV
- Keywords
- Ketamine, Learning, Memory, Habenula
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Medical Research Council, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Study start
- 25 Aug 2021 (actual)
- Primary completion
- May 2023 (estimated)
- Study completion
- May 2023 (estimated)
- First posted
- 20 Apr 2021 (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.
Ketamine's efficacy as an antidepressant is now well established yet the mechanisms underlying its antidepressant effect are yet to be fully described. Work in the animal literature and research in humans is suggestive of specific effects on anhedonia and memory reconsolidation. In this study the investigators will further explore the effects of ketamine on learning and memory as well as measuring the associated changes at neural level in a sample of healthy volunteers. Participants will be assigned to receive ketamine or placebo and complete a set of tasks which will allow the investigators to quantify the effect of ketamine on learning about reward and punishment and memory for learned reward associations 24 hours after ketamine infusion. This study will help the investigators to understand the basis of ketamine's antidepressant effects and aid the development of new treatments for depression.
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 either 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, 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
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- BMI between 18 and 30
- Participant is willing and able to give informed consent for participation in the study
- Sufficient knowledge of English language to understand and complete study tasks
- 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 signing legal documents within 7 days after the infusion visit.
Key exclusion criteria (24 listed)
- Any current or past DSM-V significant psychiatric disorder including any psychotic, mood and anxiety and borderline personality disorders
- History of, or current medical conditions which in the opinion of the investigator may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, hepatic or renal disease, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions
- First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
- History of unexplained hallucinations or impulse control problems (e.g. pathological gambling)
- Current or past history of heart rhythm disorders
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 have failed to respond to conventional monoaminergic agents. | Drug | Ketamine |
| No intervention (placebo)Placebo injection (0.9% sodium chloride) | Other | Placebo |
Primary outcome
Activation of the habenula during the Pavlovian conditioning task in response to the conditioned stimulus associated with pain stimuli and in response to the receipt of shock.
Time frame: 24 hours after ketamine infusion
Blood Oxygen Level Dependent (BOLD) signal in the habenula at the time of the shock-associated conditioned stimulus presentation and at the time of shock delivery.
Habenula response to the absence of expected reward and the receipt of an unexpected loss (i.e. a negative prediction error signal) in both the reward maximisation and loss minimisation tasks.
Time frame: 24 hours after ketamine administration
BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Preference for high-reward probability shapes learned after winning money (in the Wheel of Fortune draw) during the preference test.
Time frame: +/- 24 hours after ketamine administration
Proportion of choices where high-reward probability shapes are selected. This will be based on the difference between the perceived reward probability of shapes learned after the winning and losing of money (an area under the curve measure).
13 secondary outcomes
Ventral striatum response to the expected reward and the omission an unexpected loss (i.e. a positive prediction error signal) in both the reward maximisation and loss minimisation tasks.
Time frame: 24 hours after ketamine administration
Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test.
Time frame: 24 hours after ketamine administration
Difference in pupil response to shapes learned after winning versus losing money.
Time frame: 24 hours after ketamine administration
Amount of money earned in the learning and memory task.
Time frame: Final component completed 24 hours after ketamine administration before scanning
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time frame: 1-week after ketamine infusion
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time frame: 1-week after ketamine infusion
Recognition of positive and negative facial expressions.
Time frame: Immediately and 24 hours after ketamine infusion
Recognition of positive and negative facial expressions.
Time frame: Immediately and 24 hours after ketamine infusion
Categorisation of emotional words.
Time frame: 24 hours after ketamine infusion
Recognition of emotional words.
Time frame: 24 hours after ketamine infusion
Recall of emotional words.
Time frame: 24 hours after ketamine infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
- Individual participant dataSharing planned: Undecided
Related trials for Depression
Not yet recruitingObservational study
Validation of Wearable Core Body Temperature-Based Circadian Rhythm Digital Biomarkers
Mood Disorders, Major Depressive Diorder
RecruitingObservational study
A Prospective Study of Anxiety, Depression, and Bipolar Disorder in People
Anxiety Disorders, Depressive Disorder
RecruitingPhase 3
A Study of Vortioxetine in Japanese Pediatric Patients With Major Depressive Disorder
Major Depressive Disorder
Recruiting
Anticipated Patient and Caregiver Burden
Amyotrophic Lateral Sclerosis
Recruiting
A Study of Brief Behavioral Activation for the Treatment of Depression in Older Adult Cancer Survivors
Survivorship
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, PhD 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 Depression and Major Depressive Disorder, 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 24 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 28 Mar 2023. 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 Erdem Pulcu, PhD (01865613154, erdem.pulcu@psych.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activation of the habenula during the Pavlovian conditioning task in response to the conditioned stimulus associated with pain stimuli and in response to the receipt of shock. (time frame: 24 hours after ketamine infusion). 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?
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 28 Mar 2023.