MicroRNAs as Biomarkers in First Episode Schizophrenia (MIRFEST)
MicroRNAs in Neural-Derived Extracellular Vesicles as Biomarkers in First Episode Schizophrenia
調査の概要
状態
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Nicole Montgomery, MD
- 電話番号：949-486-9390
- メール：nmontgomery@northwell.edu
研究連絡先のバックアップ
- 名前：Juan Gallego, MD, MS
- 電話番号：718-470-4588
- メール：NMontgomery@northwell.edu
研究場所
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New York
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Glen Oaks、New York、アメリカ、11004
- 募集
- Zucker Hillside Hospital
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コンタクト：
- Nicole Montgomery
- 電話番号：9494869390
- メール：NMontgomery@northwell.edu
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-
参加基準
適格基準
就学可能な年齢
- 子
- 大人
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：非ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：First-Episode Schizophrenia - Aripiprazole/Risperidone
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.
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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.
Single baseline blood sample collected for DNA extraction and whole genome sequencing to analyze genetic variation associated with psychosis and treatment response.
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アクティブコンパレータ：Healthy volunteers
Healthy volunteers providing a single baseline blood sample for NDE miRNA analysis comparison.
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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.
Single baseline blood sample collected for DNA extraction and whole genome sequencing to analyze genetic variation associated with psychosis and treatment response.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Diagnostic performance of plasma NDE miRNA panel
時間枠：Baseline (Week 0)
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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.
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Baseline (Week 0)
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Predictive performance of baseline plasma NDE miRNA levels for treatment response
時間枠：Baseline NDE miRNAs predicting response at Week 12
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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.
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Baseline NDE miRNAs predicting response at Week 12
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Juan Gallego, MD、Northwell Health
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- R01MH143042 (米国 NIH グラント/契約)
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個々の参加者データ (IPD) を共有する予定はありますか?
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