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Ketamine as an Adjunctive Therapy for Major Depression (KARMA-dep)

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ClinicalTrials.gov Identifier: NCT03256162
Recruitment Status : Completed
First Posted : August 21, 2017
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Brief Summary:
Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.

Condition or disease Intervention/treatment Phase
Major Depressive Episode Unipolar Depression Bipolar Depression Drug: Ketamine Drug: Midazolam Phase 1

Detailed Description:
Pragmatic, randomised, controlled, parallel-group, pilot trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a depressive episode. The investigators aim to recruit up to 20 participants who will be eligible for this study and randomly allocate 10 patients to each group. The participants will undergo usual inpatient care as prescribed by their treating team for the index acute depressive episode. Both participants and assessors will be blind to treatment allocation. Consented participants will be randomly allocated in a 1:1 ratio to a four week course of either once-weekly ketamine or midazolam infusions. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. Blood samples will be taken at four time-points in the first infusion session and before the final infusion for neuroplasticity biomarker studies. Both groups will continue treatment as usual. Participates will also be followed up over a three month period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial
Actual Study Start Date : September 7, 2017
Actual Primary Completion Date : September 21, 2018
Actual Study Completion Date : September 21, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine
Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Ketamine
A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.
Other Name: Ketalar

Active Comparator: Midazolam
Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Midazolam
A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
Other Name: Hypnovel




Primary Outcome Measures :
  1. The Hamilton Rating Scale for Depression-24 item version (HRSD-24) [ Time Frame: 15 weeks ]

    The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.

    Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.

    Participants will have a baseline (T0) HRSD-24 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks.



Secondary Outcome Measures :
  1. The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16) [ Time Frame: 15 weeks ]

    The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.

    Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks.


  2. The Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: 4 weeks ]

    The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.

    Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.


  3. The Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 4 weeks ]

    The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.

    Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.


  4. Young Mania Rating Scale (YMRS; mood item) [ Time Frame: 4 weeks ]

    Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.

    Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.


  5. The Patient-Rated Inventory of Side Effects (PRISE) [ Time Frame: 4 weeks ]

    The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing.

    Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.


  6. The Montreal Cognitive Assessment (MoCA) [ Time Frame: 15 weeks ]

    The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.

    The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥18 years old
  • Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21
  • Voluntary admission for treatment of an acute depressive episode
  • Meet Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-V) criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)

Exclusion Criteria:

  • Current involuntary admission
  • Medical condition rendering unfit for ketamine/midazolam
  • Active suicidal intention
  • Dementia
  • History of Axis 1 diagnosis other than major depression
  • Electroconvulsive Therapy (ECT) administered within the last two months
  • Alcohol/substance dependence in previous six-months
  • Pregnancy or inability to confirm use of adequate contraception during the trial
  • Breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256162


Locations
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Ireland
St Patrick's University Hospital
Dublin, Ireland, D8
Sponsors and Collaborators
St Patrick's Hospital, Ireland
Investigators
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Principal Investigator: Declan M McLoughlin, PhD St Patrick's Mental Health Services and Trinity College Dublin

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Responsible Party: Prof Declan McLoughlin, Professor, St Patrick's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT03256162     History of Changes
Other Study ID Numbers: 01/17
2016-004764-18 ( EudraCT Number )
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof Declan McLoughlin, St Patrick's Hospital, Ireland:
ketamine
glutamate
Additional relevant MeSH terms:
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Ketamine
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents