Ketamine for Suicidality in Bipolar Depression

• ClinicalTrials.gov Identifier: NCT01944293
• Recruitment Status: Completed
• First Posted: September 17, 2013
• Results First Posted: June 6, 2019
• Last Update Posted: March 11, 2020
• Sponsor: New York State Psychiatric Institute
• Collaborator: Brain & Behavior Research Foundation
• Information provided by (Responsible Party): Michael Grunebaum, MD, New York State Psychiatric Institute

Tracking Information

• First Submitted Date: September 8, 2013
• First Posted Date: September 17, 2013
• Results First Submitted Date: October 3, 2018
• Results First Posted Date: June 6, 2019
• Last Update Posted Date: March 11, 2020
• Study Start Date: September 2013
• Actual Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2019)

Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation [ Time Frame: At 24 hours post-Infusion ]

Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control).

Original Primary Outcome Measures (submitted: September 12, 2013)

Reduction of Suicidal Ideation measured with the Beck Scale for Suicidal Ideation [ Time Frame: At 24 hours post-Infusion ]

Reduction of suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion with Ketamine or Midazolam, a sedative not known to reduce suicidal ideation.

Current Secondary Outcome Measures (submitted: May 14, 2019)

Change in Systolic Blood Pressure [ Time Frame: During study infusion ]

Blood pressure is measured in millimeters of mercury.

Original Secondary Outcome Measures (submitted: September 12, 2013)

Adverse events [ Time Frame: 24 hours post-infusion ]

Number of subjects with adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ketamine for Suicidality in Bipolar Depression
• Official Title: Ketamine vs. Midazolam in Bipolar Depression

Brief Summary

This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from bipolar depression.

The first drug, ketamine, is an experimental antidepressant that early studies have shown may quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the comparison drug, is not thought to reduce depression or suicidal thoughts.

Detailed Description

Patients currently taking psychiatric medications may continue them during the study. However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of benzodiazepine may need to be reduced so that they can do without it during the 24 hours pre-infusion.

Participants are randomly assigned to receive a single dose of Ketamine (0.5 mg/kg) or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study is "double-blind," meaning patients and study staff will not know which medication is in the infusion.

If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). After the infusion(s), participants will have weekly research interviews for 6 weeks to monitor response.

After post-infusion research measures are completed, all subjects will receive open clinical treatment. During open clinical treatment, medication will be changed for those patients who don't respond or whose response is transient.

Participation in this study requires a brief inpatient stay, at no cost, at the New York State Psychiatric Institute (NYSPI).

Eligible participants enrolled in this study will be offered medication management visits at no cost for a total of up to 6 months combining inpatient and outpatient treatment. At the end of the 6 months of treatment patients will be referred for ongoing care.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Bipolar Disorder
• Major Depressive Episode
• Suicidal Ideation

Intervention

• Drug: Ketamine
  Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes
  Other Names:

  • Ketalar
  • Ketamine Hydrochloride Injection
• Drug: Midazolam
  Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
  Other Name: Midazolam Injection

Study Arms

• Experimental: Ketamine
  0.5 mg/kg, I.V. (in the vein)
  Intervention: Drug: Ketamine
• Active Comparator: Midazolam
  0.02 mg/kg, I.V. (in the vein)
  Intervention: Drug: Midazolam

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 6, 2017): 16
• Original Estimated Enrollment (submitted: September 12, 2013): 30
• Actual Study Completion Date: October 2018
• Actual Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

INCLUSION CRITERIA:

• Bipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation.
• Moderate to severe suicidal ideation
• 18-65 years old
• Patients will only be enrolled if they agree to voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI) for infusion phase of treatment.
• Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, oral contraceptive pills
• Able to provide informed consent
• Subjects 61-65 years old must score 25 or higher on the Mini-Mental State Examination (MMSE) at screening

EXCLUSION CRITERIA:

• Unstable medical condition or neurological illness, including baseline hypertension (BP>140/90) or significant history of cardiovascular illness
• Significant ECG abnormality
• Pregnancy and/or lactation
• Current psychotic symptoms
• Contraindication to any study treatment
• Current or past ketamine abuse or dependence ever (lifetime); any other drug or alcohol dependence within past 6 months; suicidality only due to binge substance use or withdrawal
• Inadequate understanding of English
• Prior ineffective trial of or adverse reaction to ketamine or midazolam
• Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01944293
• Other Study ID Numbers: #6785
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Michael Grunebaum, MD, New York State Psychiatric Institute
• Study Sponsor: New York State Psychiatric Institute
• Collaborators: Brain & Behavior Research Foundation

Investigators

• Principal Investigator: Michael F Grunebaum, M.D.; Columbia Unviversity/New York State Psychiatric Institute

• PRS Account: New York State Psychiatric Institute
• Verification Date: February 2020