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

Official title

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

Overview

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.

Interventions

• Behavioral Cognitive Training
  Sessions of cognitive training exercises (15-20min each) self-administered via a web app
• Behavioral Sham Training
  Sessions of sham training exercises (15-20min each) self-administered via a web app

Primary outcome measures

• 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)]
• Montgomery Asberg Depression Rating Scale: After (Es)Ketamine Induction [Time frame: Trajectories from final 'induction phase' treatment through 4 weeks post-induction]

Secondary outcome measures (10)

• Quick Inventory of Depressive Symptoms [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-depression [Time frame: Trajectories from baseline through 12 months post-induction]
• Beck Hopelessness Scale [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-anxiety [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-anger [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-Positive Affect [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-Sleep Disturbance [Time frame: Trajectories from baseline through 12 months post-induction]
• PROMIS Measures-Cognitive Function [Time frame: Trajectories from baseline through 12 months post-induction]
• Cognitive Triad Inventory [Time frame: Trajectories from baseline through 12 months post-induction]
• Montgomery Asberg Depression Rating Scale: Naturalistic Follow-up [Time frame: Trajectories from baseline through 12 months post-induction]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 3 centers

• Kaiser Foundation Research Institute, a division of Kaiser Foundation Hospitals — Oakland
• University of Illinois at Chicago — Chicago
• Baylor College of Medicine — Houston

Identifiers

NCT: NCT06526078 · STUDY23110120 · R01MH136179 · R01MH136178

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗