Ketamine for Relapse Prevention in Recurrent Depressive Disorder

Phase 1

Terminated

• Conditions: Depression; Recurrent Depressive Disorder; Relapse; Major Depressive Disorder
• Interventions: Drug: Ketamine; Drug: Midazolam

• Registration Number: NCT02661061
• Lead Sponsor: St Patrick's Hospital, Ireland

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-10
• Study First Submitted QC: 2016-01-18
• Study First Posted: 2016-01-22
• Primary Completion: 2018-05-23
• Study Completion: 2018-05-23
• Results First Submitted: 2019-12-18
• Status Verified: 2020-01
• Results First Submitted QC: 2020-01-07
• Last Update Submitted: 2020-01-07
• Results First Posted: 2020-01-13
• Last Update Posted: 2020-01-13

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ketamine	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.
Midazolam	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.

Primary Outcome Measures

Name	Time	Method
Completion Rate for Randomised Treatment Phase	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.

Secondary Outcome Measures

Name	Time	Method
Depression Relapse Rate During Treatment and Follow-up Phase	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.

Trial Locations

Locations (1)

St Patrick's University Hospital; 🇮🇪 Dublin, Ireland