Ketamine as an adjunctive therapy for Major Depression - a randomised controlled pilot trial: The KARMA-Dep Trial

Ketamine as an adjunctive therapy for Major Depression - a randomised controlled pilot trial: The KARMA-Dep Trial - Karma-dep trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-004764-18-IE

Enrollment

Registered

2016-11-30

Start date

2017-07-24

Completion date

Unknown

Last updated

2021-10-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression

Interventions

Trade Name: Ketalar Product Name: Ketalar 10mg / ml Solution for Injection / Infusion Product Code: N01AX03 Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: Ketamine CAS Numb

Eligibility

Sex/Gender

All

Inclusion 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 DSM-IV criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Main Objective: The aim of this trial is to assess ketamine as an adjunctive therapy in major depression. We hypothesise that ketamine will accelerate the recovery time in those patients who have been admitted to hospital with a depressive episode. ;Timepoint(s) of evaluation of this end point: The primary endpoint of this pilot trial is successful completion of the trial protocol. Process outcomes such as recruitment and retention rates are the primary focus. Recruitment will cease when 40 participants have been randomised. ;Secondary Objective: 1. To assess the safety and tolerability of repeated (x4) infusions of ketamine vs. midazolam in this patient population. 2. To explore the role of ketamine-induced changes in peripheral blood neuroplasticity molecules for: (i) monitoring biological response to ketamine during the first infusion and (ii) for evaluating this biological response in treating depression. 3. To investigate epigenetic modulation of depression/stress-related genes in patients being treated with ketamine. ;Primary end point(s): The focus of a pilot trial’s outcomes is on trial process with assessment of the primary clinical outcome being secondary because the pilot itself is not designed to measure efficacy. Process outcomes that will inform a future definitive trial incluse the following: • recruitment methods and rate • willingness of participants to be randomised • willingness of participants to complete assessments • randomisation • success of blinding • ability to administer a course of ketamine infusions • medical safety and acceptability of ketamine infusions • rates of adverse dissociative and psychiatric events • adherence to allocated treatment • adherence to follow up • reasons for drop-out from treatment • reasons for drop-out from follow-up • establish a 95% confidence interval for the differences between the ketamine and midazolam groups during the 4-week treatment phase to help with power calculations for a future definitive trial	—

Measure

Time frame

Main Objective: The aim of this trial is to assess ketamine as an adjunctive therapy in major depression. We hypothesise that ketamine will accelerate the recovery time in those patients who have been admitted to hospital with a depressive episode. ;Timepoint(s) of evaluation of this end point: The primary endpoint of this pilot trial is successful completion of the trial protocol. Process outcomes such as recruitment and retention rates are the primary focus. Recruitment will cease when 40 participants have been randomised. ;Secondary Objective: 1. To assess the safety and tolerability of repeated (x4) infusions of ketamine vs. midazolam in this patient population. 2. To explore the role of ketamine-induced changes in peripheral blood neuroplasticity molecules for: (i) monitoring biological response to ketamine during the first infusion and (ii) for evaluating this biological response in treating depression. 3. To investigate epigenetic modulation of depression/stress-related genes in patients being treated with ketamine. ;Primary end point(s): The focus of a pilot trial’s outcomes is on trial process with assessment of the primary clinical outcome being secondary because the pilot itself is not designed to measure efficacy. Process outcomes that will inform a future definitive trial incluse the following: • recruitment methods and rate • willingness of participants to be randomised • willingness of participants to complete assessments • randomisation • success of blinding • ability to administer a course of ketamine infusions • medical safety and acceptability of ketamine infusions • rates of adverse dissociative and psychiatric events • adherence to allocated treatment • adherence to follow up • reasons for drop-out from treatment • reasons for drop-out from follow-up • establish a 95% confidence interval for the differences between the ketamine and midazolam groups during the 4-week treatment phase to help with power calculations for a future definitive trial

—

Secondary

Measure	Time frame
Secondary end point(s): Clinical outcomes are secondary. The primary clinical outcome is change in score of the objectively-rated 24-item Hamilton Rating Scale for Depression (HRSD-24). Standard criteria for depression severity, treatment response, remission and relapse will be used (please see definitions in "assessments") in a three-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 6 and 12 post-final infusion. Safety and tolerability outcomes consist of psychotomimetic, dissociative, cognitive and physical health effects of repeated ketamine infusions, measured before, during and after infusions using a range of validated instruments. ;Timepoint(s) of evaluation of this end point: Participants will be assessed at baseline (on admission to hospital), and on a weekly basis using the primary clinical outcome, the HRSD-24. Those who are eligible for the study, will be invited to be randomised to a four-week course of once-weekly ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6 and 12. Cognitive outcomes will be assessed following randomization and repeated at week 12. Tolerability outcomes e.g. the Young Mania Rating Scale, Brief Psychiatric Rating Scale etc, will be assessed before, during and after each infusion session. In total, follow-up will take place over three months.	—

Measure

Time frame

Secondary end point(s): Clinical outcomes are secondary. The primary clinical outcome is change in score of the objectively-rated 24-item Hamilton Rating Scale for Depression (HRSD-24). Standard criteria for depression severity, treatment response, remission and relapse will be used (please see definitions in "assessments") in a three-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 6 and 12 post-final infusion. Safety and tolerability outcomes consist of psychotomimetic, dissociative, cognitive and physical health effects of repeated ketamine infusions, measured before, during and after infusions using a range of validated instruments. ;Timepoint(s) of evaluation of this end point: Participants will be assessed at baseline (on admission to hospital), and on a weekly basis using the primary clinical outcome, the HRSD-24. Those who are eligible for the study, will be invited to be randomised to a four-week course of once-weekly ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6 and 12. Cognitive outcomes will be assessed following randomization and repeated at week 12. Tolerability outcomes e.g. the Young Mania Rating Scale, Brief Psychiatric Rating Scale etc, will be assessed before, during and after each infusion session. In total, follow-up will take place over three months.

—

Countries

Ireland

Contacts

Public ContactBronagh Gallagher

St Patrick’s Mental Health Services

bgallag@tcd.ie0035312493385

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 28, 2026