Schizophrenia Spectrum DisordersNCT05945602
Neurophysiologic Biomarkers for Cognitive Rehabilitation
An observational study of Schizophrenia Spectrum Disorders, run by VA Office of Research and Development at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia Spectrum Disorders
- What is being tested?
- Neurophysiologic Biomarker Assessments
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2023to 30 Sep 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Veterans who are enrolled in and/or receiving healthcare services at the VA San Diego Healthcare System.
Who may be able to join
- 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).
- Fluent in spoken and written English.
- No impairment in hearing or vision.
Who cannot join
- 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).
- History of significant medical or neurological illness or intellectual disability.
- Inability to comprehend or provide informed consent.
- Specific to healthy comparison subjects: past or present diagnosis of schizophrenia, schizoaffective disorder, or other chronic psychotic disorder.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
Juan Molina, MD, (202) 555-8975, Juan.Molina@va.gov
Juan Molina, MD
About this study
Official title: Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans With Chronic Psychosis
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.
Read the 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
- Being tested
- Neurophysiologic Biomarker Assessments
- Keywords
- Schizophrenia, Schizophrenia Spectrum and Other Psychotic Disorde, Mental Disorders
- Medical subject headings
- Schizophrenia, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurophysiologic Biomarker AssessmentsOther
Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Other: Neurophysiologic Biomarker Assessments | |
| 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. Receives: Other: Neurophysiologic Biomarker Assessments | |
| 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). Receives: Other: Neurophysiologic Biomarker Assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 7 days
Secondary outcomes (5)
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.
Measured: Day 1/ Baseline
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.
Measured: Day 1/ Baseline
Symptoms
Scores on the Positive and Negative Syndrome Scale (PANSS)
Measured: 1 visit
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).
Measured: Day 1/ Baseline
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).
Measured: Day 1/ Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2023
- Study start1 Oct 2023
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia Spectrum DisordersStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Juan Molina, MD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05945602
- Sponsor's protocol ID
- D4570-W
- Other IDs
- IK2RX004570
- Status last verified
- Oct 2025
- First submitted
- 6 Jul 2023
- Last updated
- 9 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans With Chronic Psychosis
- ClinicalTrials.gov ID
- NCT05945602
- Acronym / sponsor ID
- D4570-W
- Conditions
- Schizophrenia Spectrum Disorders
- Keywords
- Schizophrenia, Schizophrenia Spectrum and Other Psychotic Disorde, Mental Disorders
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 14 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Biomarker Optimization - Patients | – | Other: Neurophysiologic Biomarker AssessmentsVeterans 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). |
| Biomarker Optimization - Healthy Comparison Subjects | – | Other: Neurophysiologic Biomarker AssessmentsVeterans currently enrolled for healthcare services at the VA San Diego Healthcare System who have no history of mental illness. |
| Biomarker Validation in Chronic Psychotic Disorders | – | Other: Neurophysiologic Biomarker AssessmentsVeterans 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Veterans who are enrolled in and/or receiving healthcare services at the VA San Diego Healthcare System.
Key inclusion criteria (3 listed)
- 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).
- Fluent in spoken and written English.
- No impairment in hearing or vision.
Key exclusion criteria (4 listed)
- 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).
- History of significant medical or neurological illness or intellectual disability.
- Inability to comprehend or provide informed consent.
- Specific to healthy comparison subjects: past or present diagnosis of schizophrenia, schizoaffective disorder, or other chronic psychotic disorder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurophysiologic Biomarker AssessmentsNon-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers. | Other | Biomarker Optimization - Healthy Comparison Subjects, Biomarker Optimization - Patients, Biomarker Validation in Chronic Psychotic Disorders |
Primary outcome
1-week psychometric reliability of Aperiodic Spectral Biomarkers (neurophysiologic biomarker)
Time frame: Approximately 7 days
Estimates of aperiodic activity will be calculated from electroencephalography recordings collected at baseline (Day 1) and approximately 7 days later.
5 secondary outcomes
Cognitive training performance
Time frame: Day 1/ Baseline
Cognition
Time frame: Day 1/ Baseline
Symptoms
Time frame: 1 visit
Functioning
Time frame: Day 1/ Baseline
Functioning - Quality of Life
Time frame: Day 1/ Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Juan Molina, MD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Schizophrenia Spectrum Disorders, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Juan Molina, MD ((202) 555-8975, Juan.Molina@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-week psychometric reliability of Aperiodic Spectral Biomarkers (neurophysiologic biomarker) (time frame: Approximately 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.