Neurophysiologic Biomarkers for Cognitive Rehabilitation

Schizophrenia Spectrum Disorders Clinical Trial

Official title:

Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans With Chronic Psychosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05945602
• Other study ID #: D4570-W
• Secondary ID: IK2RX004570
• Status: Recruiting
• Start date: October 1, 2023
• Est. completion date: September 30, 2028

Study information

• Verified date: October 2023
• Source: VA Office of Research and Development
• Contact: Juan Molina, MD
• Phone: (202) 555-8975
• Email: Juan.Molina[@]va.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 30, 2028
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia
• Schizophrenia Spectrum Disorders

Intervention

Other:
• Neurophysiologic Biomarker Assessments
Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

Locations

Country	Name	City	State
United States	VA San Diego Healthcare System, San Diego, CA	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-week psychometric reliability of Aperiodic Spectral Biomarkers (neurophysiologic biomarker)	Estimates of aperiodic activity will be calculated from electroencephalography recordings collected at baseline (Day 1) and approximately 7 days later.	Approximately 7 days
Secondary	Cognitive training performance	Performance on a computerized cognitive training exercise (i.e., the "Sound Sweeps" exercise) assessing auditory processing speed. Scores range between 0-1000, with greater scores indicating worse performance.	Day 1/ Baseline
Secondary	Cognition	Performance on MATRICS Consensus Cognitive Battery (MCCB). MCCB performance will be evaluated based on age- and gender-corrected T-scores (normative mean = 50; standard deviation = 10). Higher T-score values indicate better performance.	Day 1/ Baseline
Secondary	Symptoms	Scores on the Positive and Negative Syndrome Scale (PANSS)	1 visit
Secondary	Functioning	Scores on the World Health Organization Disability Assessment Schedule (WHODAS 2.0). WHODAS summary scores are converted into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).	Day 1/ Baseline
Secondary	Functioning - Quality of Life	Scores on the World Health Organization Quality of Life Scale (WHOQOL-BREF). WHOQOL-BREF domain scores are converted into a metric ranging from 0 to 100 (where 0 = very poor quality of life; 100 = very good quality of life).	Day 1/ Baseline