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Enrolling by Invitation

NCT Number: NCT06526078

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

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.

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Key information

Conditions

Depression Behavior Behavioral Symptoms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Kaiser Foundation Research Institute, a division of Kaiser Foundation Hospitals, Oakland, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • be between the ages of 18 and 80 years
  • score ≥20 on the Montgomery-Asberg Depression Rating Scale (MADRS)
  • 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
  • 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)
  • 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
  • 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
  • possess a level of judgment and understanding sufficient to agree to all procedures required by the protocol and must sign an informed consent document
  • 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

  • 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)
  • 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
  • Concern for dementia or significant cognitive decline, per interviewer observations and impressions during screening assessments
  • Current pregnancy
  • 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

Treatment and study plan

Cognitive training

Behavioral

Sessions of cognitive training exercises (15-20min each) self-administered via a web app

Sham Training

Behavioral

Sessions of sham training exercises (15-20min each) self-administered via a web app

Primary outcomes

  1. Montgomery Asberg Depression Rating Scale: During (Es)Ketamine Induction

    Time frame: Trajectories from baseline through end of 'induction phase' treatments (up to max of 12 weeks)

    depression severity; range 0-60; high score=worse outcome

  2. Montgomery Asberg Depression Rating Scale: After (Es)Ketamine Induction

    Time frame: Trajectories from final 'induction phase' treatment through 4 weeks post-induction

    depression severity; range 0-60; high score=worse outcome

Secondary outcomes

  1. Quick Inventory of Depressive Symptoms

    Time frame: Trajectories from baseline through 12 months post-induction

    Self-reported depression (range: 0-27; higher scores = worse outcome)

  2. PROMIS Measures-depression

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome)

  3. Beck Hopelessness Scale

    Time frame: Trajectories from baseline through 12 months post-induction

    self reported to measure key aspects of hopelessness; range = 0-20, higher score=worse outcome

  4. PROMIS Measures-anxiety

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome)

  5. PROMIS Measures-anger

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome)

  6. PROMIS Measures-Positive Affect

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome)

  7. PROMIS Measures-Sleep Disturbance

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome)

  8. PROMIS Measures-Cognitive Function

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome)

  9. Cognitive Triad Inventory

    Time frame: Trajectories from baseline through 12 months post-induction

    Negative perceptions of self, future, & world (range=36-252; higher score = better outcome)

  10. Montgomery Asberg Depression Rating Scale: Naturalistic Follow-up

    Time frame: Trajectories from baseline through 12 months post-induction

    depression severity; range 0-60; high score=worse outcome

Other outcomes

  1. Implicit Association Test

    Time frame: Trajectories from baseline through 4 weeks post-induction

    performance-based "target engagement" measure of implicit self-esteem; range = -inf-inf; high score=worse outcome

  2. Columbia Suicide Severity Rating Scale--Intensity of Most Severe Ideation

    Time frame: Trajectories from baseline through 12 months post-induction

    suicidal ideation/thoughts; range 0-5; high score=worse outcome

  3. Patient Health Care Utilization Survey (PHCUS)

    Time frame: Trajectories from baseline through 12 months post-induction

    interview measure of psychiatric and healthcare service utilization

  4. PROMIS Measures-substance Use

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use Raw score range: 0-35 (higher score = worse outcome)

  5. PROMIS Measures-alcohol

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome)

  6. Acceptability, Appropriateness, and Feasibility

    Time frame: Post-Induction Week 1 assessment (approximately 1-7 days post induction)

    self-report scales of intervention acceptability, appropriateness, feasibility; range = 5-20; high score=better rating

  7. Short Form Health Survey

    Time frame: Baseline through 12 months post-induction

    Self-report measure of Quality-Adjusted Life-Years (QALYs)

  8. Client Satisfaction Questionnaire (CSQ-8)

    Time frame: Post-Induction Week 1 assessment (approximately 1-7 days post induction)

    Self-reported satisfaction; range: 8-32; high score=better rating

  9. mHealth App Usability Questionnaire (MAUQ)

    Time frame: Post-Induction Week 1 assessment (approximately 1-7 days post induction)

    Self-reported usability of cognitive training web app; range = 18-126; high score=better rating

  10. Qualitative interviews assessing implementation

    Time frame: 12 months post-induction

    Custom qualitative interviews with qualitative coding

  11. Compliance with prescribed cognitive training sessions

    Time frame: Throughout the entirety of three discrete CT "bursts"

    Compliance data from web app logs

  12. PROMIS Measures-Social Functioning

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social functioning: T-score range: 0-100 (higher score = better outcome)

  13. PROMIS Measures-Pain

    Time frame: Trajectories from baseline through 12 months post-induction

    Patient-Reported Outcomes Measurement Information System (PROMIS) measures of pain: T-score range: 0-100 (higher score = better outcome)

  14. Awe Experience Scale (AWE-S)

    Time frame: 1 week after first induction treatment

    self-report measure of awe-inspiring experiences (range: 30-210; higher score=greater awe)

  15. Implicit Association Test across follow-up

    Time frame: Trajectories through 12 months post-induction

    performance-based "target engagement" measure of implicit self-esteem; range = -inf-inf; high score=worse outcome

  16. Time to relapse

    Time frame: Baseline through 12 months post-induction

    Time-to-event for relapse to within 25% of baseline MADRS score

  17. Time to first maintenance treatment

    Time frame: Baseline through 12 months post-induction

    Time-to-event for the date of return to clinic for first maintenance treatment

Sponsors and collaborators

Lead sponsor

University of Pittsburgh

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2029
Study completion
2029
First posted
Jul 29, 2024
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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