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Ketamine for Treatment-Resistant Bipolar Disorder (KET-BD)

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ClinicalTrials.gov Identifier: NCT05004896
Recruitment Status : Not yet recruiting
First Posted : August 13, 2021
Last Update Posted : October 25, 2021
Sponsor:
Information provided by (Responsible Party):
Joshua Rosenblat, University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE August 6, 2021
First Posted Date  ICMJE August 13, 2021
Last Update Posted Date October 25, 2021
Estimated Study Start Date  ICMJE November 15, 2021
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 6, 2021)
Change in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 2 weeks ]
The MADRS is a clinician-rated scale measuring depression severity. It consists of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60. A higher score is indicative of greater depressive severity Response rates are defined as ≥ 50% decrease and Remission ≤ 10 actual score.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2021)
  • The recruitment rate [ Time Frame: 2 weeks ]
    The feasibility of ketamine as a treatment in bipolar disorder will be measured by recruitment rate
  • The retention rate [ Time Frame: 2 weeks ]
    The feasibility of ketamine as a treatment in bipolar disorder will be measured by retention rate of the study.
  • Treatment Emergent Adverse Events [ Time Frame: 2 weeks ]
    Safety will be assessed using patient-reported treatment emergent adverse events.
  • Quality of Life (QOL) [ Time Frame: 2 weeks ]
    Quality of life will be assessed using the European Quality of Life Five Dimension (EQ-5D-5L) scale, which uses a 5-component scale that evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. This scale is numbered from 0 to 100. 100 indicating the best health and 0 denoting the worst health imaginable.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 6, 2021)
  • The recruitment rate [ Time Frame: 2 weeks ]
    The feasibility of ketamine as a treatment in bipolar disorder will be measured by recruitment rate
  • The retention rate [ Time Frame: 2 weeks ]
    The feasibility of ketamine as a treatment in bipolar disorder will be measured by retention rate of the study.
  • Treatment Emergent Adverse Events [ Time Frame: 2 weeks ]
    Safety will be assessed using patient-reported treatment emergent adverse events.
  • Quality of Life (QOL) [ Time Frame: 2 weeks ]
    QOL will be assessed using the EQ-5D-5L scale, which uses a 5-component scale that evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine for Treatment-Resistant Bipolar Disorder
Official Title  ICMJE Repeated Ketamine Infusions for Treatment-Resistant Bipolar Disorder: A Randomized, Double-blind, Midazolam-controlled, Phase II Clinical Trial
Brief Summary Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing randomized control trials (RCTs) have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of four repeated sub-anesthetic doses of IV ketamine in moderate to severe TRBD. Secondary aims include evaluating effects of IV ketamine on suicidal ideations, quality of life, function and duration of effects. Herein, a two-site (University Health Network and Canadian Rapid Treatment Centre of Excellence), phase II, double-blinded, midazolam-controlled, two-week RCT evaluating the efficacy, safety and tolerability of four flexibly-dosed adjunctive ketamine infusions (0.5-0.75mg/kg infused over 40 minutes) for acute treatment of moderate to severe TRBD (type I & II) is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining the between group difference in change from baseline to day 14, using analysis of covariance (ANCOVA), with 14-day MADRS as the outcome and baseline MADRS and stratification variables (sex, bipolar type) as covariates. Secondary outcomes include evaluating response and remission rates, safety, tolerability (including treatment-emergent mania), and effects on suicidality, anxiety, quality of life, function and the duration of effects (to day 28).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Bipolar Disorder
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    50 patients will receive ketamine hydrochloride, over four infusions, flexibly dosed between 0.5 mg/kg to 0.75 mg/kg
  • Drug: Midazolam Hydrochloride
    50 patients will receive midazolam hydrochloride, over four infusions, flexibly dosed between 0.02 mg/kg to 0.03 mg/kg
Study Arms  ICMJE
  • Experimental: Ketamine
    Four infusions of ketamine will be administered over two weeks. The first two infusions will be dosed at 0.5mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.5 mg/kg to 0.75 mg/kg, depending on clinical response to first two infusions.
    Intervention: Drug: Ketamine Hydrochloride
  • Active Comparator: Midazolam
    Four infusions of midazolam will be administered over two weeks. The first two infusions will be dosed at 0.02mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.02 mg/kg to 0.03 mg/kg, depending on clinical response to first two infusions.
    Intervention: Drug: Midazolam Hydrochloride
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 6, 2021)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date October 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patient's behalf.
  2. Male or female between the age of 21 to 65, inclusive.
  3. Meets Diagnostic and Statistics Manual for Mental Health Disorders (DSM)-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode without psychotic features. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study while assessing eligibility.
  4. Patient must present with a moderate to severe depressive episode, as determined by the MADRS score greater than 21.
  5. Current depressive episode has inadequate response to two or more adequate first-line treatment trials for bipolar depression, as per the 2018 Canadian Network for Mood and Anxiety (CANMAT) Bipolar Disorder Guidelines. First line treatment trials include the use of lithium, valproate, carbamazepine, lamotrigine and/or any antipsychotic medication.
  6. Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month, including a therapeutic dose of a mood stabilizer.

Exclusion Criteria:

  1. Currently exhibiting symptoms of mania, hypomania, and/or mixed state bipolar, as determined by the Young Mania Rating Scale (YMRS) score greater than 12.
  2. Current symptoms of psychosis or a substance use disorder within the past 3 months. History of psychotic features during a mood episode will not be excluded.
  3. History of neurological disorders (including, but not limited to, uncontrolled seizure disorder, history of stroke within past 12 months, major head injuries, aneurysmal vascular disease [including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels], arteriovenous malformation, or intracerebral hemorrhage)
  4. Lifetime history of a primary psychotic disorder (including, but not limited to, schizophrenia or schizoaffective disorder)
  5. Lifetime history of ketamine use disorder
  6. Presence of active suicidality, requiring involuntary inpatient treatment or recent suicide attempts within the past 3 months.
  7. Presence of a contraindication to ketamine or midazolam, including a drug allergy, uncontrolled hypertension (baseline systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg), low or labile blood pressure, myocardial infarction within past 12 months, cardiac arrhythmia, moderate to severe hepatic impairment (i.e., Child-Pugh score of B or C), moderate or severe renal impairment (glomerular filtration rate (GFR) < 45 milliliters/min) , heart failure, or coronary artery disease
  8. Pregnant or breastfeeding women or women who intend to get pregnant. Patients who are sexually active must agree to use a highly effective contraceptive method (as outlined in section 5.11).
  9. Use of prohibited concomitant medications, including other forms of ketamine or esketamine, benzodiazepines, monoamine oxidase inhibitors, stimulants, or medical cannabis of any form.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nelson Rodrigues, MSc 416-603-5800 ext 3492 nelson.rodrigues@uhnresearch.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05004896
Other Study ID Numbers  ICMJE 21-5560
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Joshua Rosenblat, University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joshua D Rosenblat, MD,MSc Toronto Western Hospital, Psychiatry
PRS Account University Health Network, Toronto
Verification Date October 2021

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