Clinical trial NCT04939649: Ketamine As an Adjunctive Therapy for Major Depression (2)
Official title: Ketamine As an Adjunctive Therapy for Major Depression - a Randomised Controlled Trial: [KARMA-Dep (2)]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Episode
Unipolar Depression
Bipolar Depression
Keywords: ketamine
glutamate
Lead sponsor: University of Dublin, Trinity College
Sponsor class: OTHER
First posted: 2021-06-25
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pragmatic, randomised, controlled, parallel-group, superiority trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the trial is to assess the mood-rating score difference between ketamine and midazolam from before the first infusion to 24 hours after the final infusion, supplemented by a 95% confidence interval. There will also be a 24-week follow-up after the final infusion session.

Detailed description: Pragmatic, randomised, controlled, parallel-group, superiority trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a major depressive episode. The investigators aim to recruit up to 104 participants who will be eligible for this study and randomly allocate 52 patients to each group. Both participants and assessors will be blind to treatment allocation. Eligible consented participants will be randomly allocated in a 1:1 ratio to a course of up to eight infusions of either ketamine or midazolam twice weekly over up to four weeks. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. During the allocated infusions and follow-up period patients will be monitored for treatment-related adverse events relating to both mental and physical health. Participants will also be followed-up for 24 weeks after the end of the initial randomised treatment and assessment period lasting up to four weeks, in order to identify if and when relapse occurs. During the trial, both groups will continue usual inpatient care as prescribed by their treating team.

Eligibility criteria: Inclusion Criteria:

* ≥18 years old.
* Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 20 at screening and start of the first infusion.
* Voluntary admission for treatment of an acute depressive episode
* Meet DSM-5 criteria for a major depressive disorder or bipolar affective disorder (current episode depression). Diagnosis of a major depressive disorder or bipolar affective disorder (DSM-5) will be confirmed by the structured diagnostic Mini International Neuropsychiatric Interview (MINI; updated Version 7 for DSM-5).

Exclusion Criteria:

* Current involuntary admission.
* Medical condition rendering unfit for ketamine/midazolam.
* Currently taking any of the contraindicated medications that may alter the pharmacokinetics of ketamine.
* Active suicidal intention.
* Dementia.
* Lifetime history of schizophrenia or schizoaffective disorder; active anorexia nervosa or bulimia nervosa in the past 12 months; alcohol or other substance use disorder (with the exception of nicotine) in the previous six months; any DSM-5 disorder other than a major depressive episode (unipolar or bipolar) as the primary presenting problem.
* Electroconvulsive Therapy (ECT) administered within the last two months.
* Pregnancy, breastfeeding or considering becoming pregnancy whilst on the trial for up to 12 weeks after last dose or inability to confirm use of adequate contraception during the trial.
* Breastfeeding women.

Primary outcomes:
measure: Montgomery Asberg Depression Rating Scale-10 item version (MADRS)
timeFrame: 28 weeks
Secondary outcomes:
measure: The Clinician-Administered Dissociative States Scale (CADSS)
timeFrame: 4 weeks
measure: The Brief Psychiatric Rating Scale (BPRS)
timeFrame: 4 weeks
measure: Young Mania Rating Scale (YMRS; mood item)
timeFrame: 4 week
measure: Observer's Assessment of Alertness/Sedation; responsiveness subscale (OAA/S-R)
timeFrame: 4 weeks
measure: 20-item Physician Withdrawal Checklist (PWC-20)
timeFrame: 16 weeks
measure: The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR)
timeFrame: 28 weeks
measure: Patient-Rated Inventory of Side Effects (PRISE)
timeFrame: 28 weeks
measure: The Montreal Cognitive Assessment (MoCA)
timeFrame: 28 weeks
measure: EuroQol-5 dimensions-5 level scale for health status (EQ-5D-5L)
timeFrame: 28 weeks
measure: Client Service Receipt Inventory (CSRI)
timeFrame: 28 weeks
measure: Adverse events (AE) and serious adverse events (SAE) review
timeFrame: 28 weeks
measure: Concomitant Medication
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St Patrick's Univeristy Hospital
Study officials:
affiliation: University of Dublin, Trinity College and St Patrick's Mental Health Services
name: Declan M McLoughlin, PhD
role: PRINCIPAL_INVESTIGATOR
References: