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Ketamine's Actions on Rumination Mechanisms as an Antidepressant (KARMA)

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ClinicalTrials.gov Identifier: NCT04656886
Recruitment Status : Completed
First Posted : December 7, 2020
Last Update Posted : December 7, 2020
Sponsor:
Collaborator:
Johnson & Johnson
Information provided by (Responsible Party):
King's College London

Brief Summary:
Rumination and anhedonia are two of the most common characteristics of depression that persist during remission and are not easily targeted by commonly prescribed antidepressants. Ketamine, an NMDA receptor antagonist, has emerged within the last decade as a potent, fast-acting antidepressant that can significantly improve anhedonia as early as two hours after a single infusion. The brain mechanisms, however, by which ketamine exerts its antidepressant action remain largely unknown. The aim of this study is to examine the early antidepressant action of ketamine, 2h post infusion, in patients who remitted from depression using fMRI. Participants are scanned while performing a personalised, autobiographical, emotional memory task and a monetary reward task. Ketamine is expected to reduce the activation of limbic areas such as the amygdala during emotional memory recall. Increased activations after ketamine are expected in reward processing areas, including striatal regions.

Condition or disease Intervention/treatment Phase
Remission in Depression Drug: Intravenous Infusion Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: A group of remitted depressed participants will receive an intravenous infusion of ketamine or an inactive placebo, in a double-blind, cross over design. A minimun of 1 week is required between the two study sessions.
Masking: Double (Participant, Investigator)
Masking Description: Both the participants and the investigator are blind.
Primary Purpose: Basic Science
Official Title: Ketamine's Actions on Rumination Mechanisms as an Antidepressant
Actual Study Start Date : September 2014
Actual Primary Completion Date : May 2018
Actual Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants
Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketalar
0.5mg/kg of ketalar (ketamine). Single, intravenous, steady state infusion over 40min.
Drug: Intravenous Infusion
Placebo Comparator: Saline
Single, intravenous, steady state infusion over 40min.
Drug: Intravenous Infusion



Primary Outcome Measures :
  1. Ketamine's effects, 2h post infusion, on the activation of brain areas important for autobiographical emotional memory recall. [ Time Frame: 1 YEAR ]
    To investigate the role of limbic areas and NMDA receptor blockade during autobiographical memory retrieval using fMRI

  2. Ketamine's effects, 2h post infusion, on the activation of brain areas important for reward processing and anhedonia. [ Time Frame: 1 YEAR ]
    To investigate the role of striatal areas and NMDA receptor blockade during a monetary reward task using fMRI.



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Right-handed male and female volunteers with a history of depression between the ages of 18 and 50 years.
  • Good command of the English language.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of and agrees to comply with all aspects of the study.
  • Willing and able to comply with scheduled visits, dosing plan, laboratory trials and any other necessary procedures.
  • Are willing for data to be shared and disseminated after being anonymised.

Exclusion Criteria:

  • Have a current or previously diagnosed psychiatric disorder except depression.
  • Have one or more immediate family members with a current or previously diagnosed psychotic disorder.
  • Have a medically significant condition which renders them unsuitable for the study (e.g., diabetes, severe cardiovascular disease, hepatic or renal failure etc.).
  • Show MR contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) which would render them unsuitable for the study.
  • Have previously experienced an adverse response to ketamine.
  • Have excessive use of alcohol (in excess of 28 units a week), caffeine (>6 cups of coffee a day), or other drugs.
  • Have taken any other medication during the course of the study that has not been discussed - this should be documented by the investigators. (As an exception, 1g paracetamol/24 hours may be taken up to 24 hours prior to any MRI scan).
  • Have taken illicit drugs 7 days prior to admission, have consumed alcohol or caffeine within 24 hours prior to admission or have consumed nicotine within 4 hours prior to admission.
  • Have taken grapefruit juice- or Seville orange-containing products 24 hours prior to admission.
  • Use of any prescribed medication in the 3 weeks prior to enrolment or non-prescription medication (other than paracetamol) or herbal preparations in the previous 7 days.
  • Have a significant history of drugs of abuse (including benzodiazepines) or positive drugs of abuse test.
  • Had acute illness within 2 weeks before the start of study.
  • Have clinically significant abnormalities in clinical chemistry (including liver function tests), haematology or urinalysis results.
  • Have a history or presence of gastrointestinal, hepatic or renal disease or other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
  • Have been diagnosed hypertension, or supine systolic BP outside of the range of 90 to 140 mmHg and a supine diastolic BP outside the range of 40 to 90 mmHg, after a period of acclimatisation
  • Have a decrease in systolic BP of > 25 mmHg or a decrease in diastolic BP of > 15 mmHg when going from resting in bed to standing position, with or without symptoms such as dizziness or light-headedness. (For determination of orthostatic hypotension, lying and standing BP will be recorded after the subject has rested for 10 minutes and has had resting BP recorded followed by measurements taken at 1, 2 and 5 minutes after standing)
  • Had treatment in the previous 3 months with any drug known to have a well-defined potential for hepatotoxicity (e.g., halothane)
  • Subjects who, in the opinion of the investigator, should not participate in the study for reasons of safety
Publications:
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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT04656886    
Other Study ID Numbers: HR14/15-0650
First Posted: December 7, 2020    Key Record Dates
Last Update Posted: December 7, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Our consent procedures include asking for permission to share anonymised data with other researchers.

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