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

January 15, 2020 updated by: Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ireland
      • Dublin, Ireland, D8
        • St Patrick's University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Hypnovel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.
15 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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. Week 15 scores are reported.
15 weeks
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.
4 weeks
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 weeks
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.
4 weeks
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. Data below represent the number of participants from which there was an endorsement of each listed event.

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St Patrick's Hospital, Ireland

Investigators

  • Principal Investigator: Declan M McLoughlin, PhD, St Patrick's Mental Health Services and Trinity College Dublin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2017

Primary Completion (Actual)

September 21, 2018

Study Completion (Actual)

September 21, 2018

Study Registration Dates

First Submitted

August 2, 2017

First Submitted That Met QC Criteria

August 16, 2017

First Posted (Actual)

August 21, 2017

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 15, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01/17
  • 2016-004764-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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