Glutamate Emotion Memory Study

NCT05809609 | Recruiting

• 1 other identifier: GEMS
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical depression often includes a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. A licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the brain, and has been used as a treatment particularly for depression which hasn't got better with other types of medication. Glutamate plays a role in learning and memory so the investigators are interested in understanding how ketamine can affect how people with depression remember past negative and positive memories and how they experience reward. The investigators are conducting a study in depressed participants who did not improve with the standard antidepressant treatment to expand our understanding on how ketamine can influence memory, the way people understand emotions and learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks before and after the administration of the study drug, and an MRI scan after administration of the drug. MRI is a type of brain scan that allows us to see how the brain responds during for example memories of things which have happened in the past. This project will help us understand how NMDA antagonists may work in depression.

Conditions

Treatment Resistant Depression; Depression; Major Depressive Disorder

Keywords

Ketamine; Memory; Mental Health; Learning

Outcome Measures

Primary Outcomes (2)

• Change in magnitude of negative and positive valence adjectives in the autobiographical memory task using a self-reported questionnaire.

  To investigate the effects of ketamine on: \- negative emotional bias associated with autobiographical memories in TRD patients. Each negative (guilty/ashamed, depressed/sad, angry/frustrated, upset, anxious/worried, worthless) and positive (grateful, energetic/motivated, hopeful, confident, loved, happy) valence adjectives. will be rated on a scale from 0 to 100. Change in magnitude will be assessed calculating the difference in ratings of negative and positive adjectives using a self-reported questionnaire from baseline to after treatment

  -1 and 1 days after ketamine/placebo treatment

• Brain activation as measured by functional magnetic resonance in a network of areas related to autobiographical memories, including the medial prefrontal cortex and associated networks during the autobiographical memory task.

  To investigate the effects of ketamine on: \- on brain circuit associated with autobiographical memories

  1 days after ketamine/placebo treatment

Secondary Outcomes (12)

• Accuracy on a computer-based task of facial expression recognition (FERT)

  -1 day, and up to 2 hours after ketamine/placebo treatment

• Reaction time on a computer-based task of facial expression recognition (FERT)

  -1 day, and up to 2 hours after ketamine/placebo treatment

• Accuracy to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)

  Up to 2 hours after ketamine/placebo treatment

• Reaction time to classify positive and negative descriptor words using the Emotional Categorisation Task (ECAT)

  Up to 2 hours after ketamine/placebo treatment

• Number of positive and negative words correctly recalled (hits) and number of words incorrectly recalled (false alarms) using the Emotional Recall Task (EREC)

  Up to 2 hours after ketamine/placebo treatment

Study Arms (2)

Ketamine

EXPERIMENTAL

Participants in this arm will receive a single intravenous injection, 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 fail to respond to at least two antidepressant trials of adequate dose and duration.

Ketamine

No intervention (placebo) OTHER

Placebo injection (0.9% sodium chloride)

Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give informed consent for participation in the study
• Sufficiently fluent English to understand and complete the tasks
• Registered with a GP and consents to GP being informed of participation in the study
• Participants need to meet a number of concurrent clinical criteria:
• Current criteria for Major Depressive Disorder, in a current major depressive episode as determined by the SCID-5.
• Inadequate response to at least one and no more than three antidepressant treatments.
• Currently taking a licensed antidepressant at a therapeutic dose for at least four weeks.
• Pre-menopausal women and male participants engaging in sex with a risk of pregnancy must agree to use a highly effective method of contraception from Screening Visit until 30 days after receiving the study medication treatment.
• Acceptable methods of contraception include:
• Condoms
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal or transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation oral, injectable or implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• History of /or current DSM-5 bipolar disorder, schizophrenia or emotionally unstable personality disorder \[co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD) are allowed\]
• Participants who fulfil current criteria for other comorbid disorders may still be entered into the study, if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality
• Diagnosis of a major cognitive disorder or evidence of cognitive impairment
• Clinically significant risk of suicide
• Participants undergoing or who have undergone electroconvulsive therapy for the treatment of the current episode of depression
• Substance or alcohol use disorder over the past 6 months
• Regular alcohol consumption of more than 21 units a week or excessive alcohol consumption up to three days before any of the in-person study visits or inability to abstain from alcohol for more than 3 days
• Moderate cigarette use (\> 10 cigarettes per day)
• History of, or current general medical conditions that in the opinion of the Investigator may interfere with the safety of the participant or the scientific integrity of the study
• Current pregnancy (as determined by urine pregnancy test), breastfeeding, planning a pregnancy, or unwillingness to practice birth control during the course of the study
• Clinically significant abnormalities of laboratory tests, physical examination, or 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 past history of heart rhythm disorders
• Clinically significant untreated hypertension
• Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, United Kingdom

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Depressive Disorder, Major; Psychological Well-Being

Interventions

Ketamine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Catherine Harmer, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sara Costi, MD

CONTACT

01865 618303; sara.costi@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: SPONSOR

Model Details: Participants will be assigned to receive 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 26, 2022
• First Posted: April 12, 2023
• Study Start: July 1, 2022
• Primary Completion: November 28, 2024
• Study Completion: December 28, 2024
• Last Updated: May 21, 2024

Record last verified: 2024-05

Locations

GB (1)