Cognitive Training as an Adjunct to Ketamine in Real-world Clinics

A Brief Automated Neurocognitive Training to Enhance the Real-World Impact of Ketamine's Rapid Antidepressant Effect

In a sample of patients already receiving ketamine (or esketamine) treatment as part of their clinical care, this project seeks to test whether we can enhance and/or extend (es)ketamine's rapid effects by introducing helpful information delivered by a computer-based cognitive training protocol. This work could ultimately lead to the ability to treat depression more efficiently and with broader dissemination by rapidly priming the brain for helpful forms of learning.

Study Overview

• Status: Enrolling by invitation
• Conditions: Depression
• Intervention / Treatment: Behavioral: Cognitive Training; Behavioral: Sham Training

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Kaiser Foundation Research Institute, a division of Kaiser Foundation Hospitals
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. be between the ages of 18 and 80 years
2. score ≥20 on the Montgomery-Asberg Depression Rating Scale (MADRS)
3. per SCID-5-RV interview, meet DSM-5 diagnostic criteria for at least one of the following: Major Depressive Disorder, Bipolar Disorder (I or II), Persistent Depressive Disorder, or Other Specified Depressive or Bipolar Disorder
4. exhibit treatment resistance, defined as: (a) failure to respond to ≥1 adequate trials of an evidence-based treatment for mood disorder [per the Antidepressant Treatment History Form-Short Form Modified Score Sheet (ATHF-SF-Modified)] and/or (b) failure to respond to ≥1 adequate mood stabilizer or other evidence-based treatment trials (for bipolar depression patients) and/or (c) a history of intolerance during attempted trials of evidence-based treatments for mood disorders and/or (d) failure to respond to ≥1 prior treatment trials (e.g., medication, psychotherapy) for Post Traumatic Stress Disorder (PTSD)
5. be eligible and clinically enrolled for an upcoming ketamine or esketamine induction series at one of our study clinics according to that clinic's standard intake procedures
6. agree to maintain a stable schedule of concomitant psychiatric medications throughout the ketamine induction phase (minor adjustments to PRN meds and timing of meds are allowable), and for 4 weeks post-induction phase
7. possess a level of judgment and understanding sufficient to agree to all procedures required by the protocol and must sign an informed consent document
8. be willing and able to provide names and contact information for at least 1 additional emergency contact in the patient's proximal geographic area (in addition to the ketamine treatment team at the enrolling site)

Exclusion Criteria:

1. Presence of current/acute psychosis, mania, or dementia, or a diagnosis of developmental disorder with significant language and/or intellectual impairment (e.g., autism spectrum disorder)
2. Current/acute suicide risk with intent to act, defined as CSSRS past-week ideation score ≥ 4 among outpatients; patients engaged in residential or inpatient care at the time of enrollment need not meet this CSSRS score criterion, as their current/acute suicide risk is extremely low by virtue of the residential/inpatient, round-the-clock care they are already receiving at time of enrollment
3. Concern for dementia or significant cognitive decline, per interviewer observations and impressions during screening assessments
4. Current pregnancy
5. English reading level <5th grade as per patient self-report Rationale: to ensure adequate reading comprehension for verbal ASAT/sham stimuli which are presented in English

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive Training; Web-based cognitive training	Behavioral: Cognitive Training; Sessions of cognitive training exercises (15-20min each) self-administered via a web app
Sham Comparator: Sham Training; Web-based sham training	Behavioral: Sham Training; Sessions of sham training exercises (15-20min each) self-administered via a web app

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale: During (Es)Ketamine Induction	depression severity; range 0-60; high score=worse outcome	Trajectories from baseline through end of 'induction phase' treatments (up to max of 12 weeks)
Montgomery Asberg Depression Rating Scale: After (Es)Ketamine Induction	depression severity; range 0-60; high score=worse outcome	Trajectories from final 'induction phase' treatment through 4 weeks post-induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-depression	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
Beck Hopelessness Scale	self reported to measure key aspects of hopelessness; range = 0-20, higher score=worse outcome	Trajectories from baseline through 12 months post-induction
PROMIS Measures-anxiety	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-anger	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-Positive Affect	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-Sleep Disturbance	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-Cognitive Function	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome)	Trajectories from baseline through 12 months post-induction
Cognitive Triad Inventory	Negative perceptions of self, future, & world (range=36-252; higher score = better outcome)	Trajectories from baseline through 12 months post-induction
Montgomery Asberg Depression Rating Scale: Naturalistic Follow-up	depression severity; range 0-60; high score=worse outcome	Trajectories from baseline through 12 months post-induction

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Columbia Suicide Severity Rating Scale--Intensity of Most Severe Ideation	suicidal ideation/thoughts; range 0-5; high score=worse outcome	Trajectories from baseline through 12 months post-induction
Patient Health Care Utilization Survey (PHCUS)	interview measure of psychiatric and healthcare service utilization	Trajectories from baseline through 12 months post-induction
PROMIS Measures-substance Use	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use Raw score range: 0-35 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-alcohol	Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome)	Trajectories from baseline through 12 months post-induction
Short Form Health Survey	Self-report measure of Quality-Adjusted Life-Years (QALYs)	Baseline through 12 months post-induction
Qualitative interviews assessing implementation	Custom qualitative interviews with qualitative coding	12 months post-induction
PROMIS Measures-Social Functioning	Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social functioning: T-score range: 0-100 (higher score = better outcome)	Trajectories from baseline through 12 months post-induction
PROMIS Measures-Pain	Patient-Reported Outcomes Measurement Information System (PROMIS) measures of pain: T-score range: 0-100 (higher score = better outcome)	Trajectories from baseline through 12 months post-induction
Implicit Association Test across follow-up	performance-based "target engagement" measure of implicit self-esteem; range = -inf-inf; high score=worse outcome	Trajectories through 12 months post-induction
Time to relapse	Time-to-event for relapse to within 25% of baseline MADRS score	Baseline through 12 months post-induction
Implicit Association Test	performance-based "target engagement" measure of implicit self-esteem; range = -inf-inf; high score=worse outcome	Trajectories from baseline through 4 weeks post-induction
Acceptability, Appropriateness, and Feasibility	self-report scales of intervention acceptability, appropriateness, feasibility; range = 5-20; high score=better rating	Post-Induction Week 1 assessment (approximately 1-7 days post induction)
Client Satisfaction Questionnaire (CSQ-8)	Self-reported satisfaction; range: 8-32; high score=better rating	Post-Induction Week 1 assessment (approximately 1-7 days post induction)
mHealth App Usability Questionnaire (MAUQ)	Self-reported usability of cognitive training web app; range = 18-126; high score=better rating	Post-Induction Week 1 assessment (approximately 1-7 days post induction)
Compliance with prescribed cognitive training sessions	Compliance data from web app logs	Throughout the entirety of three discrete CT "bursts"
Awe Experience Scale (AWE-S)	self-report measure of awe-inspiring experiences (range: 30-210; higher score=greater awe)	1 week after first induction treatment
Time to first maintenance treatment	Time-to-event for the date of return to clinic for first maintenance treatment	Baseline through 12 months post-induction

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• 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): November 12, 2024
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Rehabilitation; Aftercare; Continuity of Patient Care; Neurological Rehabilitation; Cognitive Training
• Other Study ID Numbers: STUDY23110120; R01MH136179 (U.S. NIH Grant/Contract); R01MH136178 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results will be shared with other researchers via the NIMH Data Archive (NDA) data repository.
• IPD Sharing Time Frame: Data will become available one year after study completion and will be available indefinitely.
• IPD Sharing Access Criteria: NDA access required.

Drug and device information, study documents

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