Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboCompleted

Can a low dose of ketamine change how people with treatment-resistant depression remember their lives, deal with emotions, and make decisions?

Randomized parallel-arm placebo-controlled experimental medicine study (n=60) testing a single sub-anaesthetic IV infusion of ketamine 0.5 mg/kg versus saline in people with treatment-resistant depression to assess autobiographical memory, emotional processing and decision-making.

Target Enrollment
60 participants
Study Type
Phase NA interventional
Design
Randomized, single Blind

Detailed Description

The Glutamate Emotion Memory Study (GEMS) is a randomised, parallel-arm, placebo-controlled experimental medicine trial in adults with treatment-resistant major depressive disorder assessing a single sub-anaesthetic intravenous ketamine infusion (0.5 mg/kg over 40 minutes) versus saline.

Primary outcomes include change in valence ratings on an autobiographical memory task and fMRI measures of brain activation one day after treatment; secondary outcomes assess emotional recognition, reinforcement learning, decision-making tasks and pupillometry acutely and at follow-up.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine 0.5 mg/kg

experimental

Single IV infusion of ketamine 0.5 mg/kg over 40 minutes.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    Diluted in 40 mL 0.9% sodium chloride; infusion pump at 60 mL/h over 40 minutes.

Placebo

inactive

40 mL 0.9% sodium chloride IV infusion over 40 minutes.

Interventions

  • Placebo40 ml
    via IV• single dose• 1 doses total

    0.9% sodium chloride 40 mL; infusion pump at 60 mL/h over 40 minutes.

Participants

Ages
20 – 60
Sexes
Male & Female

Inclusion Criteria

  • 1. Male or female
  • 2. Aged 20-60 years old
  • 3. Willing and able to give informed consent for participation in the study
  • 4. Sufficiently fluent English to understand and complete the tasks
  • 5. Registered with a GP and consents to GP being informed of participation in the study
  • 6. 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
  • 7. 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
  • 8. 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
  • 9. Male participants must not donate sperm until 30 days after receiving the study medication
  • 10. Participants taking non-prescription/prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety
  • 11. Willingness to refrain from driving, cycling, or operating heavy machinery, until the following morning or a restful sleep has occurred, whichever is later
  • 12. 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

  • 1. History of or current DSM-5 bipolar disorder, schizophrenia or emotionally unstable personality disorder (co-morbid anxiety disorders and PTSD are allowed)
  • 2. Participants who fulfill current criteria for other comorbid disorders may still be entered if, in the opinion of the Investigator, the psychiatric diagnosis will not compromise safety or affect data quality
  • 3. Diagnosis of a major cognitive disorder or evidence of cognitive impairment
  • 4. Clinically significant risk of suicide
  • 5. Participants undergoing or who have undergone electroconvulsive therapy for the treatment of the current episode of depression
  • 6. Substance or alcohol use disorder over the past 6 months
  • 7. Regular alcohol consumption of more than 21 units a week or excessive alcohol consumption up to three days before any in-person study visits or inability to abstain from alcohol for more than 3 days
  • 8. Moderate cigarette use (> 10 cigarettes per day)
  • 9. History of, or current general medical conditions that in the opinion of the Investigator may interfere with safety or scientific integrity
  • 10. Current pregnancy, breastfeeding, planning a pregnancy, or unwillingness to practice birth control during the study
  • 11. Clinically significant abnormalities of laboratory tests, physical examination, or ECG unless Investigator considers inclusion safe
  • 12. Current or history of heart rhythm disorders
  • 13. Clinically significant untreated hypertension
  • 14. Any contraindication to MRI including claustrophobia, magnetic implants or inability to lie still for 1 hour or more
  • 15. Previous participation in a study using the same or similar emotional processing tasks in the last three months
  • 16. Previous lifetime use of ketamine or phencyclidine
  • 17. Participants with planned medical treatment within the study period that might interfere with the study procedures
  • 18. Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator.

Study Details

Locations

University of Oxford — Oxford, United Kingdom
NIHR Oxford cognitive health Clinical Research Facility — Oxford, United Kingdom

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