- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04850911
Reward Emotion Learning and Ketamine Study (RELAKS)
March 24, 2023 updated by: Catherine Harmer, University of Oxford
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 Overview
Status
Recruiting
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
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 Contact
- Name: Erdem Pulcu, PhD
- Phone Number: 01865613154
- Email: erdem.pulcu@psych.ox.ac.uk
Study Locations
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Oxford, United Kingdom, OX3 7JZ
- Recruiting
- University of Oxford
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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
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
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: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ketamine
Participants in this arm will receive a single intravenous, antidepressant dose of ketamine hydrochloride (0.5mg/kg)
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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.
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Placebo Comparator: Placebo
Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride).
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Placebo injection (0.9% sodium chloride)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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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.
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24 hours after ketamine infusion
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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
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BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
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24 hours after ketamine administration
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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
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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).
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+/- 24 hours after ketamine administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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BOLD signal in the ventral striatum at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
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24 hours after ketamine administration
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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
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Baseline corrected pupil dilation measured at the time of option presentation during each choice trial of the affective memory preference test.
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24 hours after ketamine administration
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Difference in pupil response to shapes learned after winning versus losing money.
Time Frame: 24 hours after ketamine administration
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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.
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24 hours after ketamine administration
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Amount of money earned in the learning and memory task.
Time Frame: Final component completed 24 hours after ketamine administration before scanning
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Between groups comparison of the total amount of money earned during the learning and memory task.
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Final component completed 24 hours after ketamine administration before scanning
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Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time Frame: 1-week after ketamine infusion
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Between groups comparison of salivary cortisol in response to Oxford Cognition Stress Task.
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1-week after ketamine infusion
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Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time Frame: 1-week after ketamine infusion
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Between groups comparison of salivary alpha amylase in response to Oxford Cognition Stress Task.
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1-week after ketamine infusion
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Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time Frame: 1-week after ketamine infusion
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Between groups comparison of heart rate in response to Oxford Cognition Stress Task.
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1-week after ketamine infusion
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Change in bio-behavioral measures of stress following laboratory induced stress administered.
Time Frame: 1-week after ketamine infusion
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Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task.
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1-week after ketamine infusion
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Recognition of positive and negative facial expressions.
Time Frame: Immediately and 24 hours after ketamine infusion
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Recognition accuracy for positive and negative facial expressions
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Immediately and 24 hours after ketamine infusion
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Recognition of positive and negative facial expressions.
Time Frame: Immediately and 24 hours after ketamine infusion
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Reaction time to recognise positive and negative facial expressions
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Immediately and 24 hours after ketamine infusion
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Categorisation of emotional words.
Time Frame: 24 hours after ketamine infusion
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Accuracy of categorisation for positive and negative descriptor words.
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24 hours after ketamine infusion
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Recognition of emotional words.
Time Frame: 24 hours after ketamine infusion
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Reaction time to categorise positive and negative descriptor words.
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24 hours after ketamine infusion
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Recall of emotional words.
Time Frame: 24 hours after ketamine infusion
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Number of words correctly (hits) and incorrectly (false alarms) recalled.
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24 hours after ketamine infusion
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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)
August 25, 2021
Primary Completion (Anticipated)
May 1, 2023
Study Completion (Anticipated)
May 1, 2023
Study Registration Dates
First Submitted
April 1, 2021
First Submitted That Met QC Criteria
April 19, 2021
First Posted (Actual)
April 20, 2021
Study Record Updates
Last Update Posted (Actual)
March 28, 2023
Last Update Submitted That Met QC Criteria
March 24, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Depressive Disorder, Treatment-Resistant
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Ketamine
Other Study ID Numbers
- RELAKS_HV
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
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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