Ketamine for Relapse Prevention in Recurrent Depressive Disorder

NCT ID: NCT02661061

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-05-23

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.

Conditions

Depression; Relapse; Recurrent Depressive Disorder; Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart.

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.

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.

Interventions

Ketamine

A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart.

Intervention Type: DRUG

Midazolam

A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.

Intervention Type: DRUG

Other Intervention Names

Ketalar; Hypnovel

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St Patrick's Hospital, Ireland

OTHER

Sponsor Role: lead

Responsible Party

Prof Declan McLoughlin

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Declan McLoughlin

Role: PRINCIPAL_INVESTIGATOR

University of Dublin, Trinity College

Locations

St Patrick's University Hospital

Dublin, , Ireland

Countries

Ireland

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-002020-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20/15

Identifier Type: -

Identifier Source: org_study_id