Efficacy of Personalizing Cognitive Remediation for Schizophrenia by Targeting Impairments in Early Auditory Processing

• ClinicalTrials.gov Identifier: NCT04554121
• Recruitment Status: Enrolling by invitation
• First Posted: September 18, 2020
• Last Update Posted: June 6, 2022
• Sponsor: Columbia University
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Alice A. Medalia, PhD, Columbia University

Tracking Information

• First Submitted Date: September 14, 2020
• First Posted Date: September 18, 2020
• Last Update Posted Date: June 6, 2022
• Actual Study Start Date: December 14, 2020
• Estimated Primary Completion Date: April 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 14, 2020)

Change in Verbal Learning [ Time Frame: 15 weeks ]

Verbal Learning is assessed with the MATRICS Consensus Cognitive Battery Verbal Learning Domain score. The primary outcome will be change in this score from pre to post treatment such that a higher value represents a better outcome.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 14, 2020)

Change in Functional Capacity [ Time Frame: 15 weeks ]

Functional Capacity is assessed with the UCSD Performance Based Skills Assessment, Brief version. The secondary outcome will be change in the total score from pre to post treatment such that a higher value represents a better outcome.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Personalizing Cognitive Remediation for Schizophrenia by Targeting Impairments in Early Auditory Processing
• Official Title: Efficacy of Personalizing Cognitive Remediation for Schizophrenia by Targeting Impairments in Early Auditory Processing

Brief Summary

The primary aim of this study is to provide confirmation that Cognitive Remediation (CR) for schizophrenia, when personalized based on pre-treatment assessment of early auditory processing ability, facilitates improved cognitive and functional outcomes. Additional aims of this study address the mechanisms of treatment effect. The study uses a repeated-measures randomized trial design.

Enrollment will be by invitation, open to individuals receiving services at select community behavioral health facilities where CR is offered. Clients who are eligible for the service, who agree to participate in research and who meet inclusion/exclusion criteria will be assessed on outcome measures and categorized via performance on the Tone Matching (TM) test, as EAP impaired (EAP-) or EAP intact (EAP+). Subsequently, EAP- and EAP+ subgroups will be randomized to either (1) Brain Basics (BB; n = 100), an EAP-enhanced CR approach or (2) Brain Training (BT; n = 100), a routine CR approach. Participants will be invited to participate in a second pre-treatment assessment to measure electrophysiologic responses to auditory stimuli. All participants will be scheduled to repeat outcome measure assessments after treatment and after a follow-up period. The EAP- group receiving BB will be invited to repeat electrophysiological paradigms post-treatment to investigate mechanisms of change related to the CR intervention. Verbal learning will be the primary outcome with functional capacity the secondary outcome. EEG is exploratory and will examine neurophysiologic markers of need for and response to EAP training.

Detailed Description

This personalized Cognitive Remediation (CR) confirmatory efficacy trial will be conducted at behavioral health facilities offering CR, located within the New York metropolitan area. Participants for this study will include adults diagnosed with schizophrenia or schizoaffective disorder, age 18-68, who have identified cognitive health as a pertinent treatment for recovery goal attainment and are seeking CR services. Individuals referred to CR may be referred for research by their treating clinician or may be self-referred. Consented individuals will receive a numeric study ID which will be used to de-identify all data collected for research.

Time 1 (baseline) outcomes assessments conducted by the research team include early auditory processing (EAP) ability, cognitive ability, and functioning. Participants will be classified as EAP impaired (EAP-) or EAP intact (EAP+). Following completion of Time 1 assessments, assignment to treatment condition will be stratified by EAP ability and randomized to Brain Basics (BB, n=100) or Brain Training (BT, n=100). Participants will be invited to participate in a separate EEG assessment of Mismatch Negativity (MMN).

CR will be conducted by trained clinicians at each performance site. CR will entail 30, 60-minute sessions administered two times a week (approximately 15 weeks). All participants will continue to receive recovery oriented therapeutic activities. Participants will be scheduled to repeat behavioral assessments at Time 2 (post-treatment) and Time 3 (follow-up) with a research team member who is blind to treatment group. The EAP- group receiving Brain Basics will also repeat EEG paradigms at Time 2 to explore mechanisms of change related to the CR intervention.

Verbal learning will be the primary outcome with functional capacity the secondary outcome. EEG is exploratory and will examine neurophysiologic markers of need for and response to EAP training. Mediation analysis will examine whether gains in cognition (verbal learning) mediate the gains in EAP and functioning. This will inform our understanding of EAP as the therapeutic change mechanism for about half of CR participants and confirm that EAP training need not be given to those CR participants with baseline intact EAP.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Schizophrenia
• Schizoaffective Disorder

Intervention

• Behavioral: Brain Basics

  Computer-based exercises targeting impairments in cognitive domains (sensory processing, processing speed, attention, working memory, memory) are paired with verbal discussions and group-based activities to strengthen metacognition and to bridge newly learned cognitive skills to everyday.

  life.

• Behavioral: Brain Training
  Computer-based exercises targeting impairments in cognitive domains (processing speed, attention, working memory, executive functions) are paired with verbal discussions and group-based activities to strengthen metacognition and to bridge newly learned cognitive skills to everyday life.

Study Arms

• Experimental: Brain Basics
  Brain Basics is a cognitive remediation intervention that emphasizes training in early auditory processing.
  Intervention: Behavioral: Brain Basics
• Active Comparator: Brain Training
  Brain Training is a cognitive remediation intervention that targets a range of cognitive abilities
  Intervention: Behavioral: Brain Training

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: September 14, 2020): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 1, 2024
• Estimated Primary Completion Date: April 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• A primary DSM-5 diagnosis of schizophrenia or schizoaffective disorder
• Psychiatrically stable, as defined by no changes in psychotropic medication or psychiatric hospitalization in the most recent 21 days
• English-speaking

Exclusion Criteria:

• Indications of Intellectual Disability as documented in medical history or measured by < 70 premorbid Full Scale IQ
• Documented auditory disorder or known visual impairment; presence of neurological conditions that are impacting brain and cognitive functioning
• Unremitted substance dependence within the past six months
• Participation in cognitive remediation in the 24 months prior

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 68 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: NCT04554121
• Other Study ID Numbers: 7982; 1R01MH123561-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Raw data will be made available for research to investigators working under a Federal Wide Assurance who meet security measures and data use agreement criteria associated with public repositories including the National Database for Clinical Trials related to Mental Illness (NDCT). Data will include baseline demographic data, and baseline and post raw data derived from primary and secondary outcome measures.
• Time Frame: A list of all data expected to be collected in the project will be submitted by January 2021. Subsequently, descriptive and raw data will be submitted on a semi-annual basis. Unpublished de-identified data will be submitted prior to study completion and will be shared within one year after project completion, or when the data are published, whichever is earlier.
• Access Criteria: Data in NIH repositories may be accessed through the NIH Data Access Committee which reviews data access and submission requests.

• Current Responsible Party: Alice A. Medalia, PhD, Columbia University
• Original Responsible Party: Alice Medalia, New York State Psychiatric Institute, Professor
• Current Study Sponsor: Columbia University
• Original Study Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Alice Medalia, Ph.D.; Columbia University

• PRS Account: Columbia University
• Verification Date: June 2022