Schizophrenia DisorderMIRFESTNCT07703670
MicroRNAs as Biomarkers in First Episode Schizophrenia
A study testing Plasma NDE miRNA Sequencing and Whole Genome Sequencing in people with Schizophrenia Disorder and Schizophreniform Disorder, run by Northwell Health at 1 site in United States.
Trial summary
This study investigates whether tiny molecules called microRNAs (miRNAs), found in special brain-derived "packages" (neural-derived extracellular vesicles, or NDEs) that travel from the brain into the blood, can serve as helpful indicators (biomarkers) for schizophrenia. Read more about this study
- Who is it for?
- Ages 15 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia Disorder, Schizophreniform Disorder, Schizoaffective Disorder
- What is being tested?
- Plasma NDE miRNA Sequencing and Whole Genome Sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2026to 1 May 2031
- Phase
- Interventional
- 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 15 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Acute first episode of psychosis with DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychosis Not Otherwise Specified (NOS)
- Current positive symptoms rated ≥4 (moderate) on one or more of these BPRS items: hallucinatory behavior, unusual thought content, grandiosity, conceptual disorganization
- Early phase of illness as defined by having taken antipsychotic drugs for a cumulative lifetime period ≤2 weeks
- Age 15 to 40
- Receiving or about to start naturalistic treatment with either aripiprazole or risperidone
- Full capacity to consent
Who cannot join
- Participant voluntarily withdraws consent at any given time during the study
- Loss of capacity to consent during the study
- Treating psychiatrist determines that the participant requires an antipsychotic medication other than aripiprazole or risperidone due to adverse effects, poor tolerability, poor response, or any other reason
- The investigator, sponsor, independent safety monitor, or DSMB determines discontinuation is necessary to protect the participant
- Pregnancy is discovered during the study
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
Zucker Hillside Hospital
Glen Oaks, New York, 11004
Nicole Montgomery, 9494869390, NMontgomery@northwell.edu
About this study
Official title: MicroRNAs in Neural-Derived Extracellular Vesicles as Biomarkers in First Episode Schizophrenia
This study investigates whether tiny molecules called microRNAs (miRNAs), found in special brain-derived "packages" (neural-derived extracellular vesicles, or NDEs) that travel from the brain into the blood, can serve as helpful indicators (biomarkers) for schizophrenia. Currently, doctors diagnose schizophrenia and monitor treatment primarily through clinical interviews, which can be slow and imprecise. This study will work with 80 individuals recently diagnosed with first-episode schizophrenia who are beginning treatment with either aripiprazole or risperidone, along with 80 healthy volunteers. Blood samples will be collected from all participants. For individuals with schizophrenia, blood will be drawn at the beginning of treatment and again after 12 weeks. By comparing patterns of brain-derived miRNAs in the blood of patients versus healthy volunteers, and by observing changes in these miRNAs during treatment, the researchers hope to discover whether these molecules can help diagnose schizophrenia more quickly and predict how well a treatment will work. If successful, this study will provide initial evidence that these miRNAs could become valuable new tools leading to earlier, more accurate diagnoses and more personalized treatment selection.
Read the detailed description
Schizophrenia is a significant psychiatric illness characterized by psychosis, social withdrawal, and cognitive difficulties leading to impaired daily functioning. Diagnosis and treatment assessment remain heavily reliant on clinical interviews, which are subjective and lack objective biological indicators. Previous research has established evidence of miRNA dysregulation in schizophrenia through genome-wide association studies, post-mortem brain tissue analysis, and biological fluid studies. A more recent and promising approach involves measuring miRNAs specifically contained within neural-derived extracellular vesicles (NDEs) isolated from plasma. These NDEs carry brain-specific miRNA cargo and can be identified in peripheral blood, offering a less invasive approach compared to cerebrospinal fluid or brain tissue.
This study addresses the identified knowledge gap by investigating plasma NDE miRNAs as novel diagnostic and treatment response biomarkers specifically in first-episode schizophrenia (FES). The focus on FES participants minimizes confounding effects associated with long-term medication use and extended illness duration. The study employs a 12-week mechanistic clinical trial design with clinical assessments, neurocognitive testing (MATRICS), and blood collection for NDE miRNA sequencing at baseline and 12 weeks. MiRNA sequencing will be performed using Illumina NovaSeq6000 following NDE isolation via L1/NCAM antibody immunoprecipitation. Statistical analysis includes differential expression analysis using DESeq, Binary Elastic Net Regression for feature selection, and machine learning models (random forests, gradient boosting, SVM) for predictive performance assessment.
- Conditions
- Schizophrenia Disorder, Schizophreniform Disorder, Schizoaffective Disorder, Psychosis Not Otherwise Specified (NOS)
- Being tested
- Plasma NDE miRNA Sequencing, Whole Genome Sequencing
- Keywords
- miRNA, biomarkers, first episode, neural derived extracellular vesicles, exosomes
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasma NDE miRNA SequencingDiagnostic test
Blood samples collected at baseline and week 12 for isolation of neural-derived extracellular vesicles (NDEs) from plasma using L1/NCAM antibody immunoprecipitation, followed by small RNA sequencing on Illumina NovaSeq6000 to identify differentially expressed miRNAs.
Whole Genome SequencingGenetic
Single baseline blood sample collected for DNA extraction and whole genome sequencing to analyze genetic variation associated with psychosis and treatment response.
| Study group | Role | What they receive |
|---|---|---|
| First-Episode Schizophrenia - Aripiprazole/Risperidone | Experimental | FES participants receiving naturalistic treatment with aripiprazole or risperidone as prescribed by their treating psychiatrist. Blood samples collected at baseline and week 12 for NDE miRNA analysis. Receives: Diagnostic Test: Plasma NDE miRNA Sequencing; Genetic: Whole Genome Sequencing |
| Healthy volunteers | Active comparator | Healthy volunteers providing a single baseline blood sample for NDE miRNA analysis comparison. Receives: Diagnostic Test: Plasma NDE miRNA Sequencing; Genetic: Whole Genome Sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance of plasma NDE miRNA panel
Sensitivity, specificity, and Area Under the Curve (AUC) of a panel of plasma NDE miRNAs in differentiating acutely psychotic First-Episode Schizophrenia (FES) participants from Healthy Volunteers (HV), assessed using Binary Elastic Net Regression and machine learning models.
Measured: Baseline (Week 0)
Predictive performance of baseline plasma NDE miRNA levels for treatment response
Predictive performance (AUC, accuracy, sensitivity, specificity) of baseline plasma NDE miRNA levels for clinical response to antipsychotic treatment (aripiprazole or risperidone). Treatment response defined as all 4 BPRS Thought Disturbance factor items below psychotic level (<4) for 2 consecutive ratings with concomitant CGI ratings of much/very much improved.
Measured: Baseline NDE miRNAs predicting response at Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2026
- Study start1 Jul 2026 (estimated)
- Primary completionMay 2031 (estimated)
- Study completion1 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia DisorderStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This study uses a parallel assignment model in which two groups of participants are followed simultaneously. Eighty first-episode schizophrenia (FES) participants are followed for 12 weeks while receiving naturalistic treatment with either aripiprazole or risperidone, as prescribed by their treating psychiatrist, with blood samples collected at baseline and week 12 for neural-derived extracellular vesicle (NDE) miRNA analysis. Eighty healthy volunteers (HV) provide a single baseline blood sample for NDE miRNA analysis to serve as a comparison group. The study is non-randomized, as the choice of antipsychotic medication is determined by the treating psychiatrist and patient preference rather than by the research team.
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juan Gallego Angel, Northwell Health
- Investigators
- Juan Gallego, MD, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07703670
- Sponsor's protocol ID
- R01MH143042
- Acronym
- MIRFEST
- Status last verified
- Jul 2026
- First submitted
- 4 Jun 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MicroRNAs in Neural-Derived Extracellular Vesicles as Biomarkers in First Episode Schizophrenia
- ClinicalTrials.gov ID
- NCT07703670
- Acronym / sponsor ID
- MIRFEST / R01MH143042
- Conditions
- Schizophrenia Disorder, Schizophreniform Disorder, Schizoaffective Disorder, Psychosis Not Otherwise Specified (NOS)
- Keywords
- miRNA, biomarkers, first episode, neural derived extracellular vesicles, exosomes
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 1 Jul 2026 (estimated)
- Primary completion
- May 2031 (estimated)
- Study completion
- 1 May 2031 (estimated)
- First posted
- 14 Jul 2026 (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.
This study investigates whether tiny molecules called microRNAs (miRNAs), found in special brain-derived "packages" (neural-derived extracellular vesicles, or NDEs) that travel from the brain into the blood, can serve as helpful indicators (biomarkers) for schizophrenia. Currently, doctors diagnose schizophrenia and monitor treatment primarily through clinical interviews, which can be slow and imprecise. This study will work with 80 individuals recently diagnosed with first-episode schizophrenia who are beginning treatment with either aripiprazole or risperidone, along with 80 healthy volunteers. Blood samples will be collected from all participants. For individuals with schizophrenia, blood will be drawn at the beginning of treatment and again after 12 weeks. By comparing patterns of brain-derived miRNAs in the blood of patients versus healthy volunteers, and by observing changes in these miRNAs during treatment, the researchers hope to discover whether these molecules can help diagnose schizophrenia more quickly and predict how well a treatment will work. If successful, this study will provide initial evidence that these miRNAs could become valuable new tools leading to earlier, more accurate diagnoses and more personalized treatment selection.
Detailed description
Schizophrenia is a significant psychiatric illness characterized by psychosis, social withdrawal, and cognitive difficulties leading to impaired daily functioning. Diagnosis and treatment assessment remain heavily reliant on clinical interviews, which are subjective and lack objective biological indicators. Previous research has established evidence of miRNA dysregulation in schizophrenia through genome-wide association studies, post-mortem brain tissue analysis, and biological fluid studies. A more recent and promising approach involves measuring miRNAs specifically contained within neural-derived extracellular vesicles (NDEs) isolated from plasma. These NDEs carry brain-specific miRNA cargo and can be identified in peripheral blood, offering a less invasive approach compared to cerebrospinal fluid or brain tissue.
This study addresses the identified knowledge gap by investigating plasma NDE miRNAs as novel diagnostic and treatment response biomarkers specifically in first-episode schizophrenia (FES). The focus on FES participants minimizes confounding effects associated with long-term medication use and extended illness duration. The study employs a 12-week mechanistic clinical trial design with clinical assessments, neurocognitive testing (MATRICS), and blood collection for NDE miRNA sequencing at baseline and 12 weeks. MiRNA sequencing will be performed using Illumina NovaSeq6000 following NDE isolation via L1/NCAM antibody immunoprecipitation. Statistical analysis includes differential expression analysis using DESeq, Binary Elastic Net Regression for feature selection, and machine learning models (random forests, gradient boosting, SVM) for predictive performance assessment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study uses a parallel assignment model in which two groups of participants are followed simultaneously. Eighty first-episode schizophrenia (FES) participants are followed for 12 weeks while receiving naturalistic treatment with either aripiprazole or risperidone, as prescribed by their treating psychiatrist, with blood samples collected at baseline and week 12 for neural-derived extracellular vesicle (NDE) miRNA analysis. Eighty healthy volunteers (HV) provide a single baseline blood sample for NDE miRNA analysis to serve as a comparison group. The study is non-randomized, as the choice of antipsychotic medication is determined by the treating psychiatrist and patient preference rather than by the research team.
| Arm | Type | Receives |
|---|---|---|
| First-Episode Schizophrenia - Aripiprazole/Risperidone | Experimental | Diagnostic Test: Plasma NDE miRNA Sequencing, Genetic: Whole Genome SequencingFES participants receiving naturalistic treatment with aripiprazole or risperidone as prescribed by their treating psychiatrist. Blood samples collected at baseline and week 12 for NDE miRNA analysis. |
| Healthy volunteers | Active comparator | Diagnostic Test: Plasma NDE miRNA Sequencing, Genetic: Whole Genome SequencingHealthy volunteers providing a single baseline blood sample for NDE miRNA analysis comparison. |
Who may qualify
- Ages
- 15 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Acute first episode of psychosis with DSM-5 diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychosis Not Otherwise Specified (NOS)
- Current positive symptoms rated ≥4 (moderate) on one or more of these BPRS items: hallucinatory behavior, unusual thought content, grandiosity, conceptual disorganization
- Early phase of illness as defined by having taken antipsychotic drugs for a cumulative lifetime period ≤2 weeks
- Age 15 to 40
- Receiving or about to start naturalistic treatment with either aripiprazole or risperidone
Key exclusion criteria (5 listed)
- Participant voluntarily withdraws consent at any given time during the study
- Loss of capacity to consent during the study
- Treating psychiatrist determines that the participant requires an antipsychotic medication other than aripiprazole or risperidone due to adverse effects, poor tolerability, poor response, or any other reason
- The investigator, sponsor, independent safety monitor, or DSMB determines discontinuation is necessary to protect the participant
- Pregnancy is discovered during the study
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 |
|---|---|---|
| Plasma NDE miRNA SequencingBlood samples collected at baseline and week 12 for isolation of neural-derived extracellular vesicles (NDEs) from plasma using L1/NCAM antibody immunoprecipitation, followed by small RNA sequencing on Illumina NovaSeq6000 to identify differentially expressed miRNAs. | Diagnostic test | First-Episode Schizophrenia - Aripiprazole/Risperidone, Healthy volunteers |
| Whole Genome SequencingSingle baseline blood sample collected for DNA extraction and whole genome sequencing to analyze genetic variation associated with psychosis and treatment response. | Genetic | First-Episode Schizophrenia - Aripiprazole/Risperidone, Healthy volunteers |
Primary outcome
Diagnostic performance of plasma NDE miRNA panel
Time frame: Baseline (Week 0)
Sensitivity, specificity, and Area Under the Curve (AUC) of a panel of plasma NDE miRNAs in differentiating acutely psychotic First-Episode Schizophrenia (FES) participants from Healthy Volunteers (HV), assessed using Binary Elastic Net Regression and machine learning models.
Predictive performance of baseline plasma NDE miRNA levels for treatment response
Time frame: Baseline NDE miRNAs predicting response at Week 12
Predictive performance (AUC, accuracy, sensitivity, specificity) of baseline plasma NDE miRNA levels for clinical response to antipsychotic treatment (aripiprazole or risperidone). Treatment response defined as all 4 BPRS Thought Disturbance factor items below psychotic level (<4) for 2 consecutive ratings with concomitant CGI ratings of much/very much improved.
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 14 Jul 2026.
- 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 Gallego, MD principal investigator
Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plasma NDE miRNA Sequencing and Whole Genome Sequencing in people with Schizophrenia Disorder and Schizophreniform Disorder, run by Northwell Health 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 6 inclusion and 5 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 14 Jul 2026. 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 Nicole Montgomery, MD (949-486-9390, nmontgomery@northwell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance of plasma NDE miRNA panel (time frame: Baseline (Week 0)). The study lists 2 primary outcomes in all. 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 14 Jul 2026.