Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Reward Emotion Learning and Ketamine Study (RELAKS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04850911
Recruitment Status : Not yet recruiting
First Posted : April 20, 2021
Last Update Posted : April 20, 2021
Sponsor:
Collaborators:
Medical Research Council
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
CatherineHarmer, University of Oxford

Tracking Information
First Submitted Date  ICMJE April 1, 2021
First Posted Date  ICMJE April 20, 2021
Last Update Posted Date April 20, 2021
Estimated Study Start Date  ICMJE April 2021
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2021)
  • 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2021)
  • 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 ]
    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. [ Time Frame: 24 hours after ketamine administration ]
    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. [ Time Frame: 24 hours after ketamine administration ]
    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. [ Time Frame: Final component completed 24 hours after ketamine administration before scanning ]
    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. [ Time Frame: 1-week after ketamine infusion ]
    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. [ Time Frame: 1-week after ketamine infusion ]
    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. [ Time Frame: 1-week after ketamine infusion ]
    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. [ Time Frame: 1-week after ketamine infusion ]
    Between groups comparison of visual analogue scale ratings in response to Oxford Cognition Stress Task.
  • Recognition of positive and negative facial expressions. [ Time Frame: Immediately and 24 hours after ketamine infusion ]
    Recognition accuracy for positive and negative facial expressions
  • Recognition of positive and negative facial expressions. [ Time Frame: Immediately and 24 hours after ketamine infusion ]
    Reaction time to recognise positive and negative facial expressions
  • Categorisation of emotional words. [ Time Frame: 24 hours after ketamine infusion ]
    Accuracy of categorisation for positive and negative descriptor words.
  • Recognition of emotional words. [ Time Frame: 24 hours after ketamine infusion ]
    Reaction time to categorise positive and negative descriptor words.
  • Recall of emotional words. [ Time Frame: 24 hours after ketamine infusion ]
    Number of words correctly (hits) and incorrectly (false alarms) recalled.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Reward Emotion Learning and Ketamine Study
Official Title  ICMJE Reward Emotion Learning and Ketamine Study
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator)
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.
Primary Purpose: Basic Science
Condition  ICMJE
  • Depression
  • Major Depressive Disorder
  • Treatment Resistant Depression
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    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.
  • Other: No intervention (placebo)
    Placebo injection (0.9% sodium chloride)
Study Arms  ICMJE
  • Experimental: Ketamine
    Participants in this arm will receive a single intravenous, antidepressant dose of ketamine hydrochloride (0.5mg/kg)
    Intervention: Drug: Ketamine Hydrochloride
  • Placebo Comparator: Placebo
    Participants in this arm will receive a single intravenous injection of an inactive placebo (0.9% sodium chloride).
    Intervention: Other: No intervention (placebo)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2021)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date November 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Erdem Pulcu, PhD 01865613154 erdem.pulcu@psych.ox.ac.uk
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04850911
Other Study ID Numbers  ICMJE RELAKS_HV
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party CatherineHarmer, University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE
  • Medical Research Council
  • Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators  ICMJE
Principal Investigator: Catherine Harmer, PhD University of Oxford
PRS Account University of Oxford
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP