Neurophysiologic Biomarkers for Cognitive Rehabilitation

NCT ID: NCT05945602

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2028-09-30

Brief Summary

Cognitive symptoms of schizophrenia interfere with daily life-from managing self-care, to more complex tasks like taking medications and living independently. Unfortunately, these cognitive symptoms are not corrected by 'standard of care' treatments (antipsychotic medications), although some schizophrenia patients may experience modest clinical and cognitive benefits from cognitive remediation. To enhance the clinical impact of cognitive remediation and other rehabilitative interventions for Veterans living with chronic psychosis, this study will develop novel brain-based tools to help identify those Veterans who are most likely to benefit from pro-cognitive therapies. These studies may advance predictive algorithms that improve functional outcomes and life quality in Veterans with schizophrenia.

Detailed Description

This is an observational study recruiting Veterans with a diagnosis of Schizophrenia (SZ) and other Chronic Psychotic Disorders and Veterans in good general health (HS) who are enrolled in and/or receiving care at the VA San Diego Healthcare System. Eighty Veterans will undergo comprehensive neurophysiological, clinical, cognitive, and functional assessments in two "phases" (Phase 1: 30 SZ, 20 HS; Phase 2: 30 SZ).

In Phase 1 (Biomarker Optimization; Aims 1 & 2), Veterans will undergo systematic neurophysiologic testing designed to elicit spectral biomarkers linked to cortical excitation and inhibition ("E/I balance") during passive and stimulated conditions on two separate test visits (1-2 weeks apart). Experimental conditions will then be optimized for internal consistency and test-retest reliability using Generalizability Theory. The optimized biomarkers will be carried forward into Phase 2 (Biomarker Validation; Aim 3), where these neurophysiologic measures will be assessed before and after Veterans with SZ undergo 1 hour of cognitive training as a demonstration of neural system target engagement.

This proposal has 3 specific aims:

Aim 1. Identify the experimental conditions that optimize the psychometric properties (i.e., sensitivity to detect individual differences) of the spectral biomarkers linked to E/I balance.

Aim 2. Characterize the relationships of spectral biomarkers with rehabilitation-relevant outcomes.

Aim 3. Evaluate the sensitivity of the optimized E/I measures in predicting performance during an acute, 1-hour exposure to computerized cognitive training.

Conditions

Schizophrenia Spectrum Disorders

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: OTHER

Study Groups

Biomarker Optimization - Patients

Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System who have a diagnosis of a chronic psychotic disorder (e.g., schizophrenia or schizoaffective disorder).

Neurophysiologic Biomarker Assessments

Intervention Type: OTHER

Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

Biomarker Optimization - Healthy Comparison Subjects

Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System who have no history of mental illness.

Neurophysiologic Biomarker Assessments

Intervention Type: OTHER

Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

Biomarker Validation in Chronic Psychotic Disorders

Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System with a diagnosis of a chronic psychotic disorder (e.g., schizophrenia or schizoaffective disorder).

Neurophysiologic Biomarker Assessments

Intervention Type: OTHER

Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

Interventions

Neurophysiologic Biomarker Assessments

Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Have a DSM-5 diagnosis of a chronic psychotic disorder (e.g., schizophrenia, schizoaffective disorder, or delusional disorder); or b) are in good general mental and physical health (i.e., no active mental health condition).

2. Fluent in spoken and written English.

3. No impairment in hearing or vision.

Exclusion Criteria

1. Active substance other than cannabis within the last 30 days as determined by self-report or positive urine toxicology (obtained as part of the screening process).

2. History of significant medical or neurological illness or intellectual disability.

3. Inability to comprehend or provide informed consent.

4. Specific to healthy comparison subjects: past or present diagnosis of schizophrenia, schizoaffective disorder, or other chronic psychotic disorder.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juan Molina, MD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego Healthcare System, San Diego, CA

Locations

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Juan Molina, MD

Role: CONTACT

Juan.Molina@va.gov

(202) 555-8975

Facility Contacts

Juan Molina, MD

Role: primary

Juan.Molina@va.gov

(202) 555-8975

Other Identifiers

IK2RX004570

Identifier Type: NIH

Identifier Source: secondary_id

View Link

D4570-W

Identifier Type: -

Identifier Source: org_study_id