Ketamine for relapse prevention in recurrent depressive disorder: a randomised, controlled pilot trial

Ketamine for relapse prevention in recurrent depressive disorder: a randomised, controlled pilot trial - KINDRED Trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-002020-37-IE

Enrollment

Registered

2015-08-04

Start date

2015-09-03

Completion date

Unknown

Last updated

2018-07-23

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

Conditions

Recurrent depressive disorder MedDRA version: 19.0 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders

Interventions

Trade Name: Ketalar Product Name: Ketalar 10mg/ml Solution for Injection/Infusion Product Code: N01AX03 Pharmaceutical Form: Solution for injection/infusion Trade Name: Hypnovel 10mg/5ml solution fo

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion criteria: Patients =18 years with DSM-V criteria for recurrent depressive disorder (RDD), a 24-item Hamilton Rating Scale for Depression (HRSD-24) score of =21, and voluntarily admitted to SPUH for treatment of the acute depressive episode will be invited to participate. The DSM-V criteria for RDD are =2 previous depressive episodes with at least 2-months (consecutive) subthreshold or no symptoms in between. (The inclusion criterion for this trial was amended on 15.9.16 and the enriched criterion of >3 episodes of depression has been removed). HRSD-24 will be repeated on a weekly basis for the duration of the inpatient stay. Upon meeting response criteria, patients will be invited to take part in the randomised controlled pilot trial. They will be assessed by physical examination, routine haematology and biochemistry investigations, and an ECG to screen for any medical conditions that might affect ability to be treated with ketamine. For the randomised pilot trial, RDD patients must have (i) received antidepressant treatment for the acute depressive episode, whether pharmacological, psychotherapeutic or multidisciplinary, (ii) achieved at least response criteria (i.e. =60% decrease from baseline HRSD-24 score and score =16), (iii) have a nominated adult who can stay with them for 24-hours on out-patient treatment days, (iv) have a Mini-Mental State Examination (MMSE) score of =24, and (v) be able to provide informed consent. 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 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40

Exclusion criteria

Exclusion criteria: Exclusion criteria: Current involuntary admission, any condition rendering patients medically unfit for ketamine or midazolam; active suicidal intention; dementia; lifetime history of bipolar disorder, post-traumatic stress disorder, or Axis 1 diagnosis other than RDD; ECT for treatment of the index depressive episode; alcohol/substance abuse in previous six-months; pregnancy or inability to confirm use of adequate contraception during the trial; inability/refusal to consent.

Design outcomes

Primary

Measure	Time frame
Main Objective: The aim of this trial is to assess ketamine for reducing relapse in successfully treated recurrent depressive disorder (RDD). We hypothesise that ketamine will reduce six month relapse rates following successful treatment of depression. ;Secondary Objective: (I) To assess safety and tolerability of repeated (4) infusions of ketamine vs. midazolam in the population of patients with successfully treated RDD (II) To explore the role of ketamine-induced changes in established peripheral blood neuroplasticity biomarkers for (i) monitoring a biological response to ketamine within the first infusion session and also (ii) for evaluating this biological response in predicting lower relapse rates in the following six months.;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 ketamine relapse prevention trial include 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 • adherence to allocated treatment • adherence to follow-up • reasons for drop-out from treatment • reasons for drop-out from follow-up • a 95% confidence interval for the difference between the ketamine;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 participant have been randomised.	—

Measure

Time frame

Main Objective: The aim of this trial is to assess ketamine for reducing relapse in successfully treated recurrent depressive disorder (RDD). We hypothesise that ketamine will reduce six month relapse rates following successful treatment of depression. ;Secondary Objective: (I) To assess safety and tolerability of repeated (4) infusions of ketamine vs. midazolam in the population of patients with successfully treated RDD (II) To explore the role of ketamine-induced changes in established peripheral blood neuroplasticity biomarkers for (i) monitoring a biological response to ketamine within the first infusion session and also (ii) for evaluating this biological response in predicting lower relapse rates in the following six months.;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 ketamine relapse prevention trial include 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 • adherence to allocated treatment • adherence to follow-up • reasons for drop-out from treatment • reasons for drop-out from follow-up • a 95% confidence interval for the difference between the ketamine;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 participant have been randomised.

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Secondary

Measure	Time frame
Secondary end point(s): Clinical outcomes are secondary. The primary clinical outcome is relapse rate at six months, measured using 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 six-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 12, 20 and 26 post-treatment-response. 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 weekly basis using the primary clinical outcome, the HRSD-24. Those who are identified as responders to acute treatment according to standard criteria, will be invited to be randomised to an eight-week course of ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6; 8;12; 20 and 26. Cognitive outcomes will be assessed following randomization and repeated at week 26. 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 six months.	—

Measure

Time frame

Secondary end point(s): Clinical outcomes are secondary. The primary clinical outcome is relapse rate at six months, measured using 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 six-month follow-up schedule which involves the HRSD-24 and other instruments at weeks 12, 20 and 26 post-treatment-response. 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 weekly basis using the primary clinical outcome, the HRSD-24. Those who are identified as responders to acute treatment according to standard criteria, will be invited to be randomised to an eight-week course of ketamine vs. midazolam infusions. The HRSD-24 will be assessed at each infusion session and at weeks 6; 8;12; 20 and 26. Cognitive outcomes will be assessed following randomization and repeated at week 26. 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 six months.

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Countries

Ireland

Contacts

Public ContactMartha Finnegan

St Patrick's University Hospital

mfinneg@tcd.ie0035312493385

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026