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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 4
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Ann Kearns, MS
- Número de teléfono: 410-402-6854
- Correo electrónico: akearns@som.umaryland.edu
Copia de seguridad de contactos de estudio
- Nombre: Mathew Glassman, MA
- Número de teléfono: 410-402-6411
- Correo electrónico: mglassman@som.umaryland.edu
Ubicaciones de estudio
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Maryland
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Catonsville, Maryland, Estados Unidos, 21228
- Maryland Psychiatric Research Center (MPRC) Outpatient Research Program (ORP); the MPRC Treatment Research Program (TRP)
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
Acepta Voluntarios Saludables
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador de placebos: Comparador de placebo: Placebo
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Control con placebo
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Comparador activo: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change in negative symptoms in schizophrenia
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Deanna L Kelly, PharmD, BCPP, University of Maryland, Baltimore
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- HP-00118919
Información sobre medicamentos y dispositivos, documentos del estudio
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