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Ketamine Interleaved With Electroconvulsive Therapy for Depression

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ClinicalTrials.gov Identifier: NCT04082858
Recruitment Status : Not yet recruiting
First Posted : September 9, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Brief Summary:
Pragmatic, randomised, controlled, parallel group, pilot clinical trial of ketamine vs. midazolam interleaved with electroconvulsive therapy (ECT) as an adjunctive treatment for a major depressive episode. 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
Depression Drug: Ketamine Drug: Midazolam Phase 1

Detailed Description:

Patients referred for treatment with ECT at St Patrick's Mental Health Services for treatment of a depressive episode will be eligible for recruitment to the clinical trial. Participants will be invited to be randomised to a course of twice-weekly ketamine or midazolam infusions for the duration of ECT. Participants will receive the first allocated infusion following the first or second treatment with ECT. Block randomisation will be independently performed. Infusions will be delivered on separate days to ECT. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions.Treatment-as-usual will continue throughout the entire trial.

Trial Interventions: participants will receive twice-weekly infusions of either ketamine at 0.5mg/Kg or midazolam at 0.045mg/Kg. All infusions will be administered by a Consultant Anaesthetist. Repeated infusions of allocated drug have been shown to be safe and well tolerated by patients with mental illness. Minor haemodynamic changes and psychotomimetic side effects can occur and will be assessed regularly during infusions and for 120 minutes afterwards. Participants will be followed-up at six weeks and three months after the final infusion to assess for relapse according to standardised criteria.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pragmatic, randomised, controlled, parallel group, pilot clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Quadruple
Primary Purpose: Health Services Research
Official Title: Ketamine Interleaved With Electroconvulsive Therapy for Depression, A Pragmatic Randomised Controlled Pilot Trial
Estimated Study Start Date : September 26, 2019
Estimated Primary Completion Date : August 19, 2020
Estimated Study Completion Date : August 19, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine
Participants will receive twice-weekly infusions of ketamine at 0.05mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist.
Drug: Ketamine
A sub-anaesthetic dose of ketamine will be administered in twice-weekly infusions
Other Name: Ketalar

Active Comparator: Midazolam
Participants will receive twice-weekly infusions of midazolam at 0.045mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist.
Drug: Midazolam
A sub-anaesthetic dose of midazolam will be administered in twice-weekly infusions
Other Name: Hyponovel




Primary Outcome Measures :
  1. Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 18 weeks ]

    A validated, 10-item, depression rating scale to measure depressive symptomatology and response to treatment. During the infusion sessions MADRS scores will be obtained immediately pre-infusion and at +60 and +120 minutes afterwards. Depression measures will be repeated at week 6 and at three-months post infusion. This outcome measure assesses the change in MADRS scores during the pilot trial.

    A course of ECT can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks.



Secondary Outcome Measures :
  1. The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16) [ Time Frame: 18 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.

    During the infusion sessions in the pilot trial QIDS scores will be obtained immediately pre-infusion and at +60 and +120 minutes afterwards. For longer-term follow-up, depression measures will be repeated at weeks 6 and three-month follow-up.

    A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks (12 weeks + 6 weeks).


  2. The Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: 6 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 infusions.

    A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks.


  3. The Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 6 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 infusion.

    A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks


  4. Young Mania Rating Scale (YMRS; mood item) [ Time Frame: 6 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 infusion.

    A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks


  5. The Patient-Rated Inventory of Side Effects (PRISE) [ Time Frame: 6 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.

    Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each infusion.

    A course of ECT can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks


  6. The Montreal Cognitive Assessment (MoCA) [ Time Frame: 18 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 the first and final infusions and at 12 weeks after the final infusion.

    A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks (12 weeks + 6 weeks).




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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
  • Able to provide informed consent
  • Voluntary admission for treatment of an acute depressive episode
  • Meet DSM-V criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
  • Montgomery Asberg Depression Rating Scale 10 item version (MADRS) score of ≥20
  • Referred for treatment with ECT
  • Sufficiently physically healthy to receive ketamine/midazolam and ECT

Exclusion Criteria:

  • Inability to provide informed consent
  • Current involuntary admission
  • History of Axis 1 diagnosis other than major depression
  • Medical condition rendering unfit for ECT
  • Active suicidal intention
  • Presence of major neurological or organic brain disorder
  • Alcohol/substance dependence in previous six-months
  • Pregnancy or inability to confirm use of adequate contraception during the trial
  • Breastfeeding women
  • Contraindications to ketamine
  • Contraindications to midazolam

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): NCT04082858


Contacts
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Contact: Declan McLoughlin, PhD 0035312493343 ext 3343 d.mcloughlin@tcd.ie
Contact: Eimear Doody, MB 0035312493375 ext 3375 eidoody@tcd.ie

Sponsors and Collaborators
St Patrick's Hospital, Ireland
Investigators
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Principal Investigator: Declan McLoughlin, PhD St Patrick's Hospital

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Responsible Party: Prof Declan McLoughlin, Professor, St Patrick's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT04082858     History of Changes
Other Study ID Numbers: 11/18
First Posted: September 9, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
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
Electroconvulsive Therapy
Additional relevant MeSH terms:
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Ketamine
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental 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