NCT02593643

Brief Summary

Depression and suicidal ideation/attempt/death are major causes of morbidity and mortality from psychiatric illnesses. In 2009, the World Health Organization listed depression as the leading cause of years lost due to disability worldwide. Suicide is the 9th most common cause of death in Canada with 1.6% of Canadians ultimately dying from suicide (Statistics Canada, 2012) and the 2nd most common cause of death in young people after accidental deaths. This information highlights the importance of finding treatments to prevent suicidal deaths. Ketamine has been shown to provide rapid treatment response for major depressive episodes both in major depressive disorder (MDD) and bipolar disorder (BD), via a single intravenous infusion which persists for at least 72 hours. The purpose of this study is to conduct a pilot trial of IV ketamine + treatment as usual (TAU) vs. midazolam (an active placebo) + TAU to estimate sample size for a full-scale RCT examining these treatments for decreasing suicidal ideation among depressed inpatients with major depressive disorder and bipolar depression. A total of 52 patients will be recruited for this trial. All subjects will be inpatients at Sunnybrook Health Sciences Centre with a diagnosis of either major depressive disorder or bipolar disorder type I or II currently depressed. Suicidal ideation must be present at baseline assessment in order to be included in the study. Thirteen subjects will be randomized to each treatment arm in each treatment stream - that is, 13 will be recruited to ketamine + TAU in the major depressive disorder stream, and 13 will be recruited to the midazolam + TAU in the major depressive stream. Likewise, 26 subjects with bipolar depression will be randomized to these two treatments.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for early_phase_1 major-depressive-disorder

Timeline
Completed

Started Jan 2016

Shorter than P25 for early_phase_1 major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 29, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 2, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

January 1, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2017

Completed
Last Updated

July 26, 2017

Status Verified

July 1, 2017

Enrollment Period

1.2 years

First QC Date

October 29, 2015

Last Update Submit

July 25, 2017

Conditions

Major Depressive DisorderBipolar I DisorderBipolar II DisorderBipolar DepressionSuicidal Ideation

Keywords

Major Depressive DisorderBipolar DisorderDepressionSuicideSuicidal IdeationKetamineMidazolamInpatients

Outcome Measures

Primary Outcomes (1)

  • Montgomery-Aspberg Depression Rating Scale (MADRS)

    two weeks

Secondary Outcomes (3)

  • Clinical Global Impression of Severity/Improvement (CGI-S, CGI-I)

    two weeks

  • Scale of Suicidal Ideation (SSI)

    two weeks

  • Columbia-Suicide Severity Rating Scale (CSSRS)

    two weeks

Study Arms (4)

ketamine+TAU - MDD

EXPERIMENTAL

Ketamine + treatment as usual (TAU) in MDD inpatients with SI

Drug: KetamineOther: Treatment as usual (TAU)

midazolam + TAU - MDD

ACTIVE COMPARATOR

Midazolam + treatment as usual (TAU) in MDD inpatients with SI

Drug: MidazolamOther: Treatment as usual (TAU)

ketamine + TAU - BD

EXPERIMENTAL

Ketamine + treatment as usual (TAU) in BD inpatients with SI

Drug: KetamineOther: Treatment as usual (TAU)

midazolam + TAU - BD

ACTIVE COMPARATOR

Midazolam + treatment as usual (TAU) in BD inpatients with SI

Drug: MidazolamOther: Treatment as usual (TAU)

Interventions

KetamineDRUG
ketamine + TAU - BDketamine+TAU - MDD
MidazolamDRUG
midazolam + TAU - BDmidazolam + TAU - MDD
Treatment as usual (TAU)OTHER

TAU includes any current treatment a patient is receiving from their primary care practitioner. In the major depressive disorder (MDD) group, TAU may include a newly initiated or longstanding antidepressant. In the bipolar depression (BD) group, TAU may include a mood stabilizer such as lithium or valproate that is a first or second line agent as per Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines (Yatham et al., 2013).

ketamine + TAU - BDketamine+TAU - MDDmidazolam + TAU - BDmidazolam + TAU - MDD

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of written informed consent
  • \[MDD stream only\] Diagnosis of major depressive disorder, currently depressed as determined by DSM-IV diagnostic criteria (confirmed using the MINI)
  • \[BD stream only\] Diagnosis of bipolar disorder, type I or type II, currently depressed as determined by DSM-IV diagnostic criteria (confirmed using the MINI)
  • Both females and males, aged 18 to 65 years
  • Inpatient status
  • Female patients of childbearing potential must have a negative urine human chorionic gonadotropin (hCG) test at enrolment and must be taking or willing to take some acceptable form of birth control during the course of the study if they are or plan to be sexually active
  • The ability to understand and comply with the requirements of the study and capable of providing informed consent
  • Suffering from suicidal ideation/attempts as evidenced by a score of \>0 on either of the SSI or CSSRS or both.

You may not qualify if:

  • Current or past psychotic symptoms
  • Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
  • Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment
  • Any pervasive developmental disorder (according to DSM-IV criteria)
  • Diagnosis of dementia (according to DSM-IV criteria)
  • Known intolerance or hypersensitivity to ketamine or midazolam as judged by the investigator
  • Significant medical condition that would contraindicate the use of ketamine, midazolam or that is untreated and would need urgent attention (as determined by treating physician)
  • Medical conditions that would significantly affect absorption, distribution, metabolism, or excretion of ketamine or midazolam
  • Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
  • Any clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
  • Pregnancy (or female of child-bearing age not using adequate contraception) or lactation
  • A positive β-hCG test at enrollment
  • Involvement in the planning and conduct of the study
  • Previous enrollment or randomisation of treatment in the present study
  • Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sunnybook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (3)

  • Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry. 2012 Oct 1;72(7):537-47. doi: 10.1016/j.biopsych.2012.05.003. Epub 2012 Jun 16.

    PMID: 22705040BACKGROUND

  • World Health Organization (WHO). Global health risks: mortality and burden of disease attributable to selected major risks. 2009. [http://www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf; accessed April 4, 2013]

    BACKGROUND

  • Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013 Feb;15(1):1-44. doi: 10.1111/bdi.12025. Epub 2012 Dec 12.

    PMID: 23237061BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, MajorBipolar DisorderSuicidal IdeationDepressionSuicide

Interventions

KetamineMidazolamTherapeutics

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersBipolar and Related DisordersSelf-Injurious BehaviorBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Scientist

Study Record Dates

First Submitted

October 29, 2015

First Posted

November 2, 2015

Study Start

January 1, 2016

Primary Completion

April 1, 2017

Study Completion

April 1, 2017

Last Updated

July 26, 2017

Record last verified: 2017-07

Locations

CA(1)