Ketamine + Cognitive Training for Suicidality in the Medical Setting

This project seeks to identify the acute and longer-term impact of a single dose of intravenous ketamine among suicidal patients referred for psychiatric consultation/liaison in the medical inpatient setting. The investigators will then test whether ketamine's rapid effects can be extended by introducing helpful information delivered by a computer-based training protocol. This work could ultimately lead to the ability to treat suicidality more efficiently and with broader dissemination by rapidly priming the brain for helpful forms of learning.

Study Overview

• Status: Enrolling by invitation
• Conditions: Suicide, Attempted
• Intervention / Treatment: Drug: Intravenous ketamine; Behavioral: Cognitive training; Behavioral: Sham Training

Detailed Description

NOTE: Edits were made to the outcome measures sections to improve clarity regarding the a priori analytic plan with respect to the "Time Frame" of measurements and to reduce redundancies. Timepoints that will be analyzed as trajectories over windows of time and measurements that will be analyzed as composites are now more clearly specified. The previous entries correctly identified all relevant measures and timepoints, but implied incorrectly that each timepoint/measure would be analyzed in isolation.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants who receive ketamine will:

1. be between the ages of 18 and 65 years
2. be a medical inpatient referred for psychiatric consultation/liaison due to suicidality and determined by psychiatric C/L to require inpatient psychiatric hospitalization
3. possess a level of judgment and understanding sufficient to agree to all procedures required by the protocol and must sign an informed consent document
4. be deemed an appropriate and reasonable medical candidate for intravenous ketamine by a physician authorized to prescribe medication to the patient during inpatient hospitalization

Exclusion Criteria:

1. Presence of current/acute psychosis with significant thought disruption, mania, delirium, or dementia, or a diagnosis of developmental disorder with significant language and/or intellectual impairment
2. Mini-Mental State Exam (MMSE) < 21
3. Current pregnancy or breastfeeding
4. Reading level <5th grade as per WRAT-3 reading subtest AND patient declines to have all questionnaire items and task instructions read aloud to them at all assessment points
5. Past intolerance or hypersensitivity to ketamine or esketamine
6. Patients taking St John's Wort
7. Patients who have received ECT in the past 1 month prior to intake
8. Patients at ongoing risk for severe substance or alcohol withdrawal related issues (e.g., delirium tremens, severe opiate withdrawal) or who present with substance-induced psychosis
9. Arrested or incarcerated individuals brought in by the legal system for medical stabilization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine + Cognitive Training	Drug: Intravenous ketamine; Single subanesthetic infusion of ketamine (0.5mg/kg); Behavioral: Cognitive training; 8 sessions of computer-based cognitive training
Sham Comparator: Ketamine + Sham Training	Drug: Intravenous ketamine; Single subanesthetic infusion of ketamine (0.5mg/kg); Behavioral: Sham Training; 8 sessions of computer-based sham training
Active Comparator: No-infusion (TAU) + Cognitive Training	Behavioral: Cognitive training; 8 sessions of computer-based cognitive training
Sham Comparator: No-infusion (TAU) + Sham Training	Behavioral: Sham Training; 8 sessions of computer-based sham training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scale for Suicide Ideation	suicidal ideation/thoughts; range 0-38; high score=worse outcome	Trajectories from 24hrs through 1 month
Montgomery Asberg Depression Rating Scale	depression severity; range 0-60; high score=worse outcome	Trajectories from 24hrs through 1 month
Suicidal behaviors: medical chart review and Columbia Suicide Severity Rating Scale (CSSRS)	composite measure of # unique occurrences of any suicidal outcome (recorded via either measure) including: re-attempt, re-hospitalization for suicidality, suicide behaviors, or completed suicide	Trajectories from 24hrs through 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adult Suicide Ideation Questionnaire	suicidal ideation/thoughts; range 0-150; high score=worse outcome	Trajectories from 24hrs through 12 months
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	Trajectories from 24hrs through 12 months
Scale for Suicide Ideation	suicidal ideation/thoughts; range 0-38; high score=worse outcome	Trajectories from 1 month through 12 months
Montgomery Asberg Depression Rating Scale	depression severity; range 0-60; high score=worse outcome	Trajectories from 1 month through 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implicit Association Test	performance-based "target engagement" measure of suicidal cognition; range = -inf-inf; high score=worse outcome	Trajectories from 24hrs through 1 week
Implicit Association Test	performance-based "target engagement" measure of suicidal cognition; range = -inf-inf; high score=worse outcome	Trajectories from 1 week through 12 months
Acceptability: infusion	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Satisfaction: infusion	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Future likelihood of use: infusion	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Ease of use: Cognitive Training	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Helpfulness: Cognitive Training	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Satisfaction: Cognitive Training	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)
Future likelihood of use: Cognitive Training	self-report slider scale rating; range = 0-100; high score=better rating	Post-CT assessment (approximately +5 days post-randomization)

Collaborators and Investigators

• Sponsor: Rebecca Price
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Rebecca B Price, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Estimated): March 2, 2026
• Study Completion (Estimated): March 2, 2026

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide; Suicide, Attempted; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: STUDY19100041 (Part 2); R01MH124983 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No