Clinical trial NCT05945602: Neurophysiologic Biomarkers for Cognitive Rehabilitation
Official title: Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans With Chronic Psychosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Schizophrenia Spectrum Disorders
Keywords: Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorde
Mental Disorders
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2023-07-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Veterans who are enrolled in and/or receiving healthcare services at the VA San Diego Healthcare System.

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.

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.

Primary outcomes:
measure: 1-week psychometric reliability of Aperiodic Spectral Biomarkers (neurophysiologic biomarker)
timeFrame: Approximately 7 days
Secondary outcomes:
measure: Cognitive training performance
timeFrame: Day 1/ Baseline
measure: Cognition
timeFrame: Day 1/ Baseline
measure: Symptoms
timeFrame: 1 visit
measure: Functioning
timeFrame: Day 1/ Baseline
measure: Functioning - Quality of Life
timeFrame: Day 1/ Baseline
Other outcomes:
Locations:
city: San Diego
country: United States
facility: VA San Diego Healthcare System, San Diego, CA
state: California
Study officials:
affiliation: VA San Diego Healthcare System, San Diego, CA
name: Juan Molina, MD
role: PRINCIPAL_INVESTIGATOR
References: