Clinical Trial of an IL-23 Inhibitor for Immune Activation in Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia
Randomized Double-Blind Clinical Trial of an IL-23 Inhibitor for Immune Activation in People With Schizophrenia
This 16 week clinical trial investigates a precision-medicine approach to schizophrenia by targeting a biologically distinct subgroup,-approximately one-third of patients-characterized by the presence of anti-gliadin antibodies (AGA IgG+) which is associated with elevated inflammation in the IL-23/IL-17 immune axis (Th17 pathway). This specific biotype is associated with pronounced negative symptoms, cognitive deficits, and reduced white matter integrity. Building on evidence that this pathway can be modulated to improve clinical outcomes, we are conducting a randomized, double-blind clinical trial of mirikizumab, an FDA-approved monoclonal antibody targeting IL-23, in addition to current antipsychotics, in schizophrenia patients who are positive for AGA IgG.
The primary objective is to determine whether mirikizumab - a repurposed FDA approved monoclonal antibody treatment inhibiting IL-23-- will be superior to placebo in treating experiential (e.g., anhedonia and asociality) negative symptoms and cognitive impairments. Secondary aims will be to assess changes in T-cell subtypes and relative abundance by gene expression, peripheral cytokines, and neuroimaging markers (in a smaller subset). By focusing on this patient subgroup, who are identified by their immune status, the research aims to provide a targeted, revolutionary treatment for symptoms that have traditionally remained resistant to standard antipsychotic therapies.
This protocol includes a screening phase, with a separate consent form which is intended to identify those with AGA IgG antibodies. This screening portion will also serve to compare other aspects of immune functioning and the TH17 pathway between patient groups and controls in order to further characterize and show that Th17 (and similar immune cell lines) are different between AGA IgG positive, AGA IgG negative and healthy controls of either status.
研究概览
研究类型
注册 (估计的)
阶段
- 第四阶段
联系人和位置
学习联系方式
- 姓名：Ann Kearns, MS
- 电话号码：410-402-6854
- 邮箱：akearns@som.umaryland.edu
研究联系人备份
- 姓名：Mathew Glassman, MA
- 电话号码：410-402-6411
- 邮箱：mglassman@som.umaryland.edu
学习地点
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Maryland
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Catonsville、Maryland、美国、21228
- Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)
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参与标准
资格标准
适合学习的年龄
- 成人
接受健康志愿者
描述
Inclusion Criteria: Screening
- Age range of 18-64
- Schizophrenia Group: Meet meet DSM 5 criteria for schizophrenia or schizoaffective disorder
- Healthy Control Group: Does NOT meet DSM 5 criteria for schizophrenia or schizoaffective disorder, bipolar disorder, or major depressive disorder.
Exclusion Criteria: Screening
- Known current active infection, or taking an immunosuppressive medications (e.g. oral scheduled corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs), or the scheduled use of anti-inflammatory medications, including NSAIDs (e.g. ibuprofen, celecoxib, or naproxen) or aspirin > 81 mg on a daily basis will be excluded.
- Score of less than 10/12 on the ESC
Inclusion Criteria: Clinical Trial
- Age range of 18-64
- Meet meet DSM 5 criteria for schizophrenia or schizoaffective disorder
- Personal and Social Performance (PSP) Scale score of ≤70.
- Treated with the same antipsychotic for at least 30 days and having received a constant therapeutic dose for at least 15 days prior to study entry
- One test in the past of elevated AGA IgG antibodies (AGA IgG > 15)
Exclusion Criteria: Clinical Trial
- Current infection, including HIV, and Hepatitis C (blood draw) or tuberculosis (TB*); or an organic brain disorder or medical condition, whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol.
- Currently taking immunosuppressive medications (e.g. oral scheduled corticosteroids, chemotherapy or transplantation or HIV/AIDs associated drugs); or the scheduled use of anti-inflammatory medications, including NSAIDs (e.g. ibuprofen, celecoxib, or naproxen) or aspirin > 81 mg on a daily basis will be excluded. The use of PRN anti-inflammatory agents will be allowed
- Score of less than 10/12 on the ESC
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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安慰剂比较：安慰剂对照品：安慰剂
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安慰剂对照
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有源比较器：IL-23
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IL-23 induction dosage at initiation, week 4 and week 8 treatments consisting of 300 mg intravenously (IV) over at least 30 minutes, and one maintenance dose at week 12 consisting of 200 mg subcutaneously (given as either one injection of 200 mg or as two consecutive injections of 100 mg each).
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in negative symptoms in schizophrenia
大体时间：16 weeks
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Change in negative symptoms in schizophrenia, specific experiential negative symptoms (i.e., motivation and pleasure) using The Clinical Assessment Interview for Negative Symptoms (CAINS) is a clinician-rated tool developed to assess the negative symptoms of schizophrenia, aligning with the NIMH's consensus on negative symptom domains. It comprises two main subscales: the Motivation and Pleasure (MAP) scale and the Expression (EXP) scale. The CAINS-MAP subscale specifically evaluates deficits in motivation, social engagement, and hedonic experience across social, vocational, and recreational contexts. The 0-4 Scoring System:0: No impairment (within the range of normal variation)
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16 weeks
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合作者和调查者
调查人员
- 首席研究员：Deanna L Kelly, PharmD, BCPP、University of Maryland, Baltimore
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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