Reward Emotion Learning and Ketamine Study

NCT04850911 | Unknown

• 1 other identifier: RELAKS_HV
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Major Depressive Disorder; Treatment Resistant Depression

Keywords

Ketamine; Learning; Memory; Habenula

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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).

  +/- 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.

  24 hours after ketamine administration

• Pupil dilation (measured by an eye tracker device) in response to decision values in the affective memory preference test.

  24 hours after ketamine administration

• Difference in pupil response to shapes learned after winning versus losing money.

  24 hours after ketamine administration

• Amount of money earned in the learning and memory task.

  Final component completed 24 hours after ketamine administration before scanning

• Change in bio-behavioral measures of stress following laboratory induced stress administered.

  1-week after ketamine infusion

Study Arms (2)

Ketamine

EXPERIMENTAL

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

Drug: Ketamine Hydrochloride

Placebo

PLACEBO COMPARATOR

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

Other: No intervention (placebo)

Interventions

Ketamine Hydrochloride DRUG

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.

Ketamine

No intervention (placebo) OTHER

Placebo injection (0.9% sodium chloride)

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council: collaborator
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: collaborator

Study Sites (1)

University of Oxford

Oxford, OX3 7JZ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Catherine Harmer, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erdem Pulcu, PhD

CONTACT

01865613154; erdem.pulcu@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 20, 2021
• Study Start: August 25, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

GB (1)