MicroRNAs as Biomarkers in First Episode Schizophrenia

NCT07703670 | Recruiting DMC

• 1 other identifier: R01MH143042
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Schizophrenia Disorder; Schizophreniform Disorder; Schizoaffective Disorder; Psychosis Not Otherwise Specified (NOS)

Keywords

miRNA; biomarkers; first episode; neural derived extracellular vesicles; exosomes

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline NDE miRNAs predicting response at Week 12

Study Arms (2)

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.

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.

Diagnostic Test: Plasma NDE miRNA Sequencing; Genetic: Whole Genome Sequencing

Interventions

Plasma NDE miRNA Sequencing DIAGNOSTIC_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.

First-Episode Schizophrenia - Aripiprazole/Risperidone; Healthy volunteers

Whole Genome Sequencing GENETIC

Single baseline blood sample collected for DNA extraction and whole genome sequencing to analyze genetic variation associated with psychosis and treatment response.

First-Episode Schizophrenia - Aripiprazole/Risperidone; Healthy volunteers

Eligibility Criteria

• Age: 15 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Zucker Hillside Hospital

Glen Oaks, New York, 11004, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Juan Gallego, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole Montgomery, MD

CONTACT

949-486-9390; nmontgomery@northwell.edu

Juan Gallego, MD, MS

CONTACT

718-470-4588; NMontgomery@northwell.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Laboratory staff conducting NDE isolation and miRNA sequencing will be blinded to participant group identity (FES vs. HV) to decrease risk of bias during laboratory analyses.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator, Board certified Psychiatrist

Model Details: 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.

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: July 14, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)