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Ketamine for Relapse Prevention in Recurrent Depressive Disorder (KINDRED)

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ClinicalTrials.gov Identifier: NCT02661061
Recruitment Status : Terminated (Inadequate recruitment)
First Posted : January 22, 2016
Results First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Tracking Information
First Submitted Date  ICMJE December 10, 2015
First Posted Date  ICMJE January 22, 2016
Results First Submitted Date  ICMJE December 18, 2019
Results First Posted Date  ICMJE January 13, 2020
Last Update Posted Date January 13, 2020
Study Start Date  ICMJE December 2015
Actual Primary Completion Date May 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 7, 2020)
Completion Rate for Randomised Treatment Phase [ Time Frame: 2 years ]
The outcomes for this pilot trial are process outcomes, primarily rates of recruitment and retention. Thus, the completion rate for the randomised treatment phase is the primary outcome. The study is not designed to assess efficacy.
Original Primary Outcome Measures  ICMJE
 (submitted: January 18, 2016)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2020)
Depression Relapse Rate During Treatment and Follow-up Phase [ Time Frame: 8 months ]
Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) was used to assess for the main clinical outcome, the relapse rate over six months. Criteria for relapse are ≥10 point increase in HRSD-24 compared to 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). Hospital admission, and deliberate self-harm/suicide also constitute relapse. Relapse may also occur during the eight-week treatment phase and is captured here.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2016)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine for Relapse Prevention in Recurrent Depressive Disorder
Official Title  ICMJE Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial
Brief Summary Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam for depression relapse prevention in persons at high risk. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
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.
Primary Purpose: Other
Condition  ICMJE
  • Depression
  • Relapse
  • Recurrent Depressive Disorder
  • Major Depressive Disorder
Intervention  ICMJE
  • Drug: Ketamine
    A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart.
    Other Name: Ketalar
  • Drug: Midazolam
    A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.
    Other Name: Hypnovel
Study Arms  ICMJE
  • Experimental: Ketamine
    Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
    Intervention: Drug: Ketamine
  • 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.
    Intervention: Drug: Midazolam
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 31, 2018)
9
Original Estimated Enrollment  ICMJE
 (submitted: January 18, 2016)
40
Actual Study Completion Date  ICMJE May 23, 2018
Actual Primary Completion Date May 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≥18 years old
  • Hamilton Rating Scale for Depression, 24-item (HRSD-24) score of ≥21
  • Voluntary admission for treatment of acute depressive episode
  • Meet DSM-IV criteria for recurrent depressive disorder (RDD): ≥2 previous depressive episodes with at least 2-months(consecutive) subthreshold or no symptoms in between PLUS(to enrich the sample for those at high risk for relapse) must also have experienced ≥3 major depressive episodes(including index episode) within the previous 2 years

For the randomised pilot trial, RDD patients must have:

  • received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
  • ≥60% decrease from baseline HRSD-24 score and score ≤16
  • Standardised Mini-Mental State Examination (sMMSE) score of ≥24
  • able to provide informed consent

Exclusion Criteria:

  • Current involuntary admission
  • Medical condition rendering unfit for ketamine/midazolam
  • Active suicidal intention
  • Dementia
  • History of Axis 1 diagnosis other than RDD
  • Electroconvulsive therapy (ECT) for treatment of current depressive episode
  • Alcohol/substance abuse in previous six months
  • Pregnancy or inability to confirm use of adequate contraception during the trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ireland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02661061
Other Study ID Numbers  ICMJE 20/15
2015-002020-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: None envisaged: data will be anonymised
Responsible Party Prof Declan McLoughlin, St Patrick's Hospital, Ireland
Study Sponsor  ICMJE St Patrick's Hospital, Ireland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Declan McLoughlin University of Dublin, Trinity College
PRS Account St Patrick's Hospital, Ireland
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP