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Ketamine for Depression Relapse Prevention Following ECT (KEEP-WELL)

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ClinicalTrials.gov Identifier: NCT02414932
Recruitment Status : Completed
First Posted : April 13, 2015
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
Health Research Board, Ireland
Information provided by (Responsible Party):
Prof Declan McLoughlin, St Patrick's Hospital, Ireland

Brief Summary:
Depression affects up to 20% of people in their lifetime and can be a severe debilitating illness. Indeed, the World Health Organisation has estimated that depression will soon be the second leading contributor to the burden of disease worldwide. One of the big problems for patients and doctors is that currently available antidepressant drugs and psychotherapies do not work for 30% of people. However, about 60% of such treatment-resistant patients will recover fully with electroconvulsive therapy (ECT). Even though it was developed over 75 years ago, ECT continues to be the most powerful treatment for severe, often life-threatening, depression. Despite that, we have recently reported that severe depression symptoms return (called a "relapse") in nearly 40% of such responders within six months of completing a course of ECT. Actually, such high relapse rates are seen for all patients with treatment-resistant depression, irrespective of what treatment they have received. There is thus an urgent need for better treatments to prevent relapse and one such possibility is an old drug called ketamine. Ketamine blocks the activity of glutamate, one of the major chemical messenger systems in the brain. Because of this effect it is sometimes used as an anaesthetic but it can also make you feel a bit "high" and so is sometimes abused as a recreational drug. Fortunately, in small doses it is quite safe. Recently, it has been found that ketamine has a remarkably rapid, but brief, antidepressant effect, including reducing suicidal thoughts. We wish to evaluate ketamine as a way to reduce relapse rates in people who have just been treated successfully with ECT for severe depression. Developing such a new treatment, and understanding how it works, would be of tremendous benefit to persons with severe depression, their families, and the wider society.

Condition or disease Intervention/treatment Phase
Depression Drug: Ketamine Drug: Midazolam Early Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Ketamine for Depression Relapse Prevention Following ECT: a Randomised Pilot Trial With Blood Biomarker Evaluation
Study Start Date : April 2015
Actual Primary Completion Date : April 7, 2017
Actual Study Completion Date : April 7, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine
Ketamine (ketamine hydrochloride 0.5 mg/kg; Pfizer Healthcare Ireland)) will be made up as a 50 ml colourless saline solution and administered as a slow infusion over 40 minutes using an intravenous infusion pump. A course of up to four once-weekly infusions will be administered. Infusions will be discontinued by the Anaesthetist if there are persisting haemodynamic changes (i.e. heart rate >110/minute or systolic/diastolic blood pressure (BP) >180/100 or >20% increase above pre-infusion BP for more than 15 minutes) that do not respond to beta-blocker therapy.
Drug: Ketamine
Ketamine hydrochloride 0.5 mg/kg; Pfizer Healthcare Ireland
Other Name: Ketalar

Active Comparator: Midazolam
Midazolam (0.045 mg/kg; Roche Products Ireland Ltd) will be made up as a 50 ml colourless saline solution and administered as a slow infusion over 40 minutes using an intravenous infusion pump. A course of up to four once-weekly infusions will be administered.
Drug: Midazolam
Midazolam 0.045 mg/kg; Roche Products Ireland Ltd
Other Name: Hypnovel




Primary Outcome Measures :
  1. Recruitment rate [ Time Frame: 30 months ]
    Process outcomes are primary in this pilot trial. These include recruitment methods and rate and will be assessed following the completion of the trial


Secondary Outcome Measures :
  1. Depression relapse rate [ Time Frame: 6 months ]
    Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) will be 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 Phase 2 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, further ECT, and deliberate self-harm/suicide also constitute relapse.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥18 years with unipolar major depressive disorder (DSM-IV)
  • 24-item Hamilton Rating Scale for Depression (HRSD-24) score of ≥21
  • Referred for ECT

For the randomised Phase 2, patients must have

  • received a substantial course of ECT in Phase 1 (i.e. at least five sessions)
  • achieved at least response criteria (i.e. ≥60% decrease from baseline HRSD-24 score and score ≤16 on two consecutive weekly ratings)
  • have a nominated adult who can stay with them for 24-hours on out-patient treatment days
  • Mini-Mental State Examination (MMSE) score of ≥24
  • able to provide informed consent

Exclusion Criteria:

  • Any condition rendering patient medically unfit for ECT; general anaesthesia, ketamine or midazolam - assessed by physical examination, routine haematology and biochemistry investigations prior to enrolment in Phase I (routine care)
  • Active suicidal intention
  • Dementia, intellectual disability, or MMSE <24
  • Lifetime history of bipolar affective disorder
  • Current history of post-traumatic stress disorder
  • Other Axis I diagnosis (DSM-IV)
  • ECT in the six months prior to recruitment
  • Alcohol dependence or substance misuse in the six months prior to recruitment
  • Pregnancy or breast-feeding
  • Residing in a nursing home
  • Prisoner
  • Diagnosis of terminal illness
  • Inability or refusal to provide valid informed consent

Information from the National Library of Medicine

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): NCT02414932


Locations
Ireland
St Patrick's University Hospital
Dublin, Ireland, 8
Sponsors and Collaborators
St Patrick's Hospital, Ireland
Health Research Board, Ireland
Investigators
Principal Investigator: Declan M McLoughlin St Patrick's Hospital/Trinity College

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof Declan McLoughlin, Professor, St Patrick's Hospital, Ireland
ClinicalTrials.gov Identifier: NCT02414932     History of Changes
Other Study ID Numbers: SPUH 05/14
2014-004262-14 ( EudraCT Number )
First Posted: April 13, 2015    Key Record Dates
Last Update Posted: June 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Prof Declan McLoughlin, St Patrick's Hospital, Ireland:
ketamine
electroconvulsive therapy
glutamate

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents