Ketamine for Relapse Prevention in Recurrent Depressive Disorder (KINDRED)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02661061|
Recruitment Status : Terminated (Inadequate recruitment)
First Posted : January 22, 2016
Last Update Posted : August 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Depression Relapse Recurrent Depressive Disorder Major Depressive Disorder||Drug: Ketamine Drug: Midazolam||Phase 1|
Participants will be recruited at admission to St Patrick's University Hospital for treatment of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-diagnosed recurrent unipolar depression and followed-up weekly to assess recovery according to standard criteria. Blood samples for epigenetic studies will be taken at baseline. Treatment-as-usual will continue throughout the entire trial. Participants who meet standardised response criteria will then be invited to be randomised to course of four two-weekly ketamine or midazolam (active comparator) 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.Trial Interventions: participants will receive four two-weekly infusions of either ketamine at 0.05mg/kg or midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Repeated infusions of ketamine 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 200 minutes afterwards.
Participants will be followed up over six months to assess for relapse according to standardised criteria. This is the highest-risk period for relapse and investigators hypothesize that ketamine will provide additional neurotrophic support (assessed by the laboratory biomarker project) which will result in lower relapse rates when compared to midazolam.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||A randomised, double-blind, placebo-controlled study designed to assess feasibility of recruitment, randomisation and retention.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Masking took place by sealed envelope random allocation and double blinding of participants and raters was assessed throughout. The anaesthesiologist administering infusions was aware of the allocation.|
|Official Title:||Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||May 23, 2018|
|Actual Study Completion Date :||May 23, 2018|
Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart.
Other Name: Ketalar
Active Comparator: Midazolam
Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.
Other Name: Hypnovel
- Process outcomes [ Time Frame: 2 years ]The primary outcomes for this pilot trial are process outcomes to inform a future definitive trial, e.g. completion of assessments; success of blinding. Although some attrition can be expected during the six-month follow-up period, information collected on rates and reasons for drop-out will form a valuable feasibility outcome. Non-compliance is not expected due to intravenous administration of agents. Rates of recruitment, attrition and retention will be reported.
- Relapse of recurrent depressive disorder: 24-item Hamilton Rating Scale for Depression scores [ Time Frame: 6 months after recruitment for individual participants, 2.5 years for total study. ]
The primary clinical outcome is the relapse rate at six months as measured by the primary clinical measure, the 24-item Hamilton Rating Scale for Depression (HRSD-24). To enter the study patients must score ≥21 at baseline.
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 (if indicated, additional follow-ups will be arranged).
During the infusion sessions in the pilot trial HRSD-24 scores will be obtained 60 minutes before the infusion begins and at +120 and +240 minutes afterwards. Baseline scores on sleep and appetite items will be maintained for repeated measures within one day. Scores on the HRSD-24 over six-months will be reported.
- Tolerability of infusion regime; performance on assessments for psychomimetic effects, physical health measures, and cognitive assessments [ Time Frame: 8 weeks for individual participants, two years for total study . ]
We will use the following instruments before, during (+35-40 mins) and after (+240 mins) ketamine infusions: Dissociative effects: Clinician-Administered Dissociative States Scale (CADSS), Psychotomimetic effects: positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS), Mood elevation: Young Mania Rating Scale (YMRS; mood item).
These instruments will be used to assess cognitive outcomes at responder baseline (prior to randomisation) and during the pilot trial: one day after the first and fourth infusions and at six-months. Addenbrooke's Cognitive Examination III (ACE-3, Forward and Backward Digit Spans, Trail Making Test (Part A + B). Physical health measures of: Heart rate, blood pressure, pulse oximetry, and ECG before and during infusions and for a further 200 minutes, and the Patient-Rated Inventory of Side Effects (PRISE) will be used to document other general adverse events by patients before, during (+35-40 mins) and after (+240 mins) infusions.
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): NCT02661061
|St Patrick's University Hospital|
|Dublin, Ireland, 8|
|Principal Investigator:||Declan McLoughlin||Trinity College Dublin|