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Reward Emotion Learning and Ketamine Study (RELAKS)

Primary Purpose

Depression, Major Depressive Disorder, Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Ketamine Hydrochloride
No intervention (placebo)
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Depression focused on measuring Ketamine, Learning, Memory, Habenula

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of OxfordRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine

Placebo

Arm Description

Participants in this arm will receive a single intravenous, antidepressant dose of ketamine hydrochloride (0.5mg/kg)

Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride).

Outcomes

Primary Outcome Measures

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.
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.
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).

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
Recognition of positive and negative facial expressions.
Recognition accuracy for positive and negative facial expressions
Recognition of positive and negative facial expressions.
Reaction time to recognise positive and negative facial expressions
Categorisation of emotional words.
Accuracy of categorisation for positive and negative descriptor words.
Recognition of emotional words.
Reaction time to categorise positive and negative descriptor words.
Recall of emotional words.
Number of words correctly (hits) and incorrectly (false alarms) recalled.

Full Information

First Posted
April 1, 2021
Last Updated
March 24, 2023
Sponsor
University of Oxford
Collaborators
Medical Research Council, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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1. Study Identification

Unique Protocol Identification Number
NCT04850911
Brief Title
Reward Emotion Learning and Ketamine Study
Acronym
RELAKS
Official Title
Reward Emotion Learning and Ketamine Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 25, 2021 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Oxford
Collaborators
Medical Research Council, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression, Major Depressive Disorder, Treatment Resistant Depression
Keywords
Ketamine, Learning, Memory, Habenula

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigator
Masking Description
All members of the study team will be blinded to the condition a participant is allocated to with the exception of the team member responsible for administering the drug/placebo.
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketamine
Arm Type
Experimental
Arm Description
Participants in this arm will receive a single intravenous, antidepressant dose of ketamine hydrochloride (0.5mg/kg)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride).
Intervention Type
Drug
Intervention Name(s)
Ketamine Hydrochloride
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
No intervention (placebo)
Intervention Description
Placebo injection (0.9% sodium chloride)
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
24 hours after ketamine infusion
Title
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.
Description
BOLD signal in the habenula at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Time Frame
24 hours after ketamine administration
Title
Preference for high-reward probability shapes learned after winning money (in the Wheel of Fortune draw) during the preference test.
Description
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).
Time Frame
+/- 24 hours after ketamine administration
Secondary Outcome Measure Information:
Title
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.
Description
BOLD signal in the ventral striatum at the time of outcome presentation in both the reward maximisation and loss minimisation tasks.
Time Frame
24 hours after ketamine administration
Title
Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test.
Description
Baseline corrected pupil dilation measured at the time of option presentation during each choice trial of the affective memory preference test.
Time Frame
24 hours after ketamine administration
Title
Difference in pupil response to shapes learned after winning versus losing money.
Description
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.
Time Frame
24 hours after ketamine administration
Title
Amount of money earned in the learning and memory task.
Description
Between groups comparison of the total amount of money earned during the learning and memory task.
Time Frame
Final component completed 24 hours after ketamine administration before scanning
Title
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Description
Between groups comparison of salivary cortisol in response to Oxford Cognition Stress Task.
Time Frame
1-week after ketamine infusion
Title
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Description
Between groups comparison of salivary alpha amylase in response to Oxford Cognition Stress Task.
Time Frame
1-week after ketamine infusion
Title
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Description
Between groups comparison of heart rate in response to Oxford Cognition Stress Task.
Time Frame
1-week after ketamine infusion
Title
Change in bio-behavioral measures of stress following laboratory induced stress administered.
Description
Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task.
Time Frame
1-week after ketamine infusion
Title
Recognition of positive and negative facial expressions.
Description
Recognition accuracy for positive and negative facial expressions
Time Frame
Immediately and 24 hours after ketamine infusion
Title
Recognition of positive and negative facial expressions.
Description
Reaction time to recognise positive and negative facial expressions
Time Frame
Immediately and 24 hours after ketamine infusion
Title
Categorisation of emotional words.
Description
Accuracy of categorisation for positive and negative descriptor words.
Time Frame
24 hours after ketamine infusion
Title
Recognition of emotional words.
Description
Reaction time to categorise positive and negative descriptor words.
Time Frame
24 hours after ketamine infusion
Title
Recall of emotional words.
Description
Number of words correctly (hits) and incorrectly (false alarms) recalled.
Time Frame
24 hours after ketamine infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Erdem Pulcu, PhD
Phone
01865613154
Email
erdem.pulcu@psych.ox.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Harmer, PhD
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oxford
City
Oxford
ZIP/Postal Code
OX3 7JZ
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Reward Emotion Learning and Ketamine Study

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