A Study of Probiotics in Patients With Acute Ischemic Stroke (PRO-STROKE)
Placebo-Controlled, Double-Blind, Phase 2 Trial of Probiotic Supplementation in Acute Ischemic Stroke
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Ischemic stroke induces a rapid and sustained systemic inflammatory response that contributes to secondary brain injury, post-stroke complications, and long-term functional outcome. In addition to well-characterized neuroinflammatory mechanisms, increasing evidence indicates that stroke profoundly alters the gut microbiota through autonomic dysfunction, reduced intestinal motility, altered permeability, and frequent exposure to antibiotics and hospital-related stressors. This stroke-induced dysbiosis has been linked to systemic immune activation, impaired immune homeostasis, and increased susceptibility to infections, all of which negatively affect recovery after stroke.
Experimental studies have demonstrated that the composition and functional capacity of the gut microbiota influence ischemic brain injury and post-stroke inflammation. Alterations in microbial community structure can modulate peripheral immune responses, including myeloid cell activation and cytokine production, and affect levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, exert immunomodulatory effects by regulating innate and adaptive immune responses and maintaining intestinal barrier integrity. Reduced SCFA availability has been associated with enhanced systemic inflammation and adverse neurological outcomes in experimental stroke models.
Clinical observations further support the relevance of the gut-brain axis in stroke. Patients with acute ischemic stroke exhibit rapid changes in gut microbiome composition, reduced microbial diversity, and shifts in specific taxa that correlate with stroke severity, systemic inflammation, and functional outcome. However, whether targeted modulation of the gut microbiota after stroke can reproducibly alter microbial community structure and downstream biological processes in humans remains unclear. Existing clinical studies of probiotics and synbiotics have shown anti-inflammatory effects in various non-neurological conditions, but data from adequately powered randomized controlled trials in acute ischemic stroke are lacking.
The probiotic formulation OMNi-BiOTiC® SR-9 contains multiple well-characterized bacterial strains combined with a prebiotic matrix designed to support bacterial viability and metabolic activity. This formulation has demonstrated immunomodulatory properties and a favorable safety profile in previous clinical applications. Administered early after stroke, probiotic supplementation represents a low-risk, non-invasive strategy to counteract stroke-associated dysbiosis, stabilize gut microbial community structure, and potentially restore microbiota-derived metabolic and immune signaling.
Given the complexity and inter-individual variability of the human gut microbiome, global measures of microbial community composition, such as beta diversity, represent sensitive and biologically meaningful endpoints to capture probiotic-induced changes. Assessing microbiome beta diversity at 90 days allows sufficient time for microbial ecosystem restructuring and stabilization following acute stroke and hospitalization, while still reflecting effects initiated during the early post-stroke phase.
Therefore, this randomized, placebo-controlled phase 2 trial is designed to evaluate whether daily oral administration of OMNi-BiOTiC® SR-9 for 90 days can induce measurable changes in gut microbiome beta diversity in patients with acute ischemic stroke. Secondary objectives address clinical outcome, specific microbial taxa, and circulating SCFAs to provide complementary mechanistic insights and inform the design of future outcome-driven trials.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Lan Liu, PhD
- Número de teléfono: 8683911991
- Correo electrónico: liulan1815@outlook.com
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Age ≥ 60 years;
- Diagnosis of ischemic stroke; (1)Ischemic stroke is defined as clinically manifest acute neurological deficits linked to an acute cerebral infarct in the anterior circulation; (2)Central retinal artery occlusion or likely central retinal artery occlusion are not considered ischemic strokes in the context of this trial;
- Randomization within 72 hours of symptom onset;
- Ability to provide written informed consent;
- Baseline NIHSS >=4;
- Pre-stroke mRS <=2;
Exclusion Criteria:
- Suspected lack of compliance;
- Presence of moderate to severe dysphagia;
- Current participation in other interventional trials or recent participation (within the last 30 days) in an interventional trial;
- Known allergy or hypersensitivity to trial compounds components or placebo;
- No known history before randomization of imminently life-shortening medical conditions or any other reason, including any physical, psychological, or psychiatric condition that in the investigator's opinion would compromise the safety or interfere with the subject's participation in this study, or would make the subject an unsuitable candidate to receive study drug, or would put the subject at risk by participating in the study;
- Malignant diseases including active malignancies with a life expectancy of less than 3 months;
- Major gastro-intestinal (GI) surgery, chronic inflammatory diseases of the gut and significant GI-neoplasms;
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 |
|---|---|
|
Experimental: Probiotic group
Subjects receive the probiotic supplement OMNi-BiOTiC® SR-9 orally twice daily, one sachet each time, with each sachet containing approximately 7.5 × 10^9 live bacteria.
|
Each sachet contains approximately 7.5 × 10^9 live bacteria.
Administered orally twice daily.
|
|
Comparador de placebos: Placebo group
Subjects receive placebo orally twice daily, one sachet each time, consisting of an equal volume of starch, with appearance, packaging, and administration method identical to the probiotic preparation.
|
Identical in appearance, packaging, and administration method to the probiotic preparation, with no active ingredients.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Beta diversity of gut microbiota at Day 90±3 (treatment vs. placebo)
Periodo de tiempo: Day 90 ± 3 days
|
Beta diversity assessed using stool samples at Day 90±3.
PERMANOVA will be used to evaluate differences in microbial community composition between treatment arms.
This endpoint captures global, community-level alterations of gut microbiota reflecting probiotic-induced ecosystem restructuring in the post-stroke setting, rather than changes in individual taxa alone.
|
Day 90 ± 3 days
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Modified Rankin Scale (mRS) score at Day 90±3
Periodo de tiempo: Day 90 ± 3 days
|
The mRS evaluates degree of disability or dependence in daily activities post-stroke.
Scores range from 0 to 6, with higher scores indicating worse outcome.
|
Day 90 ± 3 days
|
|
Changes in gut microbiota diversity and relative abundance of Prevotella copri at Day 90±3
Periodo de tiempo: Baseline to Day 90 ± 3 days
|
Temporal beta diversity indices (TBI) will assess changes in beta diversity from baseline to Day 90±3.
Changes in alpha diversity will be calculated using Abundance-based Coverage Estimator (ACE), expressed as ACE at Day 90±3 minus ACE at baseline.
Relative abundance of Prevotella copri in stool samples at Day 90±3 will be compared between verum and placebo groups.
|
Baseline to Day 90 ± 3 days
|
|
Serum concentrations of short-chain fatty acids (SCFAs) at Day 90±3
Periodo de tiempo: Baseline and Day 90 ± 3 days
|
Measured SCFAs include acetate, butyrate, and propionate.
Evaluates metabolic changes associated with gut microbiota modulation.
|
Baseline and Day 90 ± 3 days
|
|
EQ-5D-5L at day 90
Periodo de tiempo: Day 90 ± 3 days
|
EQ-5D-5L assesses health-related quality of life across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), higher scores indicate better health.
EQ-VAS ranges from 0 to 100, higher scores indicate better self-perceived health.
|
Day 90 ± 3 days
|
|
Barthel Index at day 90
Periodo de tiempo: Day 90 ± 3 days
|
The Barthel Index is an ordinal scale consisting of 10 activities of daily living (including feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, bed-to-chair transfer, ambulation, and stair climbing).
Total scores range from 0 to 100, with higher scores indicating greater functional independence and better prognosis.
|
Day 90 ± 3 days
|
|
Safety Outcomes
Periodo de tiempo: Baseline to Day 90 ± 3 days
|
The safety outcome is the number of reported adverse events (AEs) and serious adverse events (SAEs) in the verum group compared to the placebo group.
All events will be assessed for severity, causality, and relevance, and reported in accordance with regulatory guidelines.
|
Baseline to Day 90 ± 3 days
|
|
Change in modified Rankin Scale (mRS) score from baseline to Day 90±3
Periodo de tiempo: Baseline to Day 90 ± 3 days
|
Calculated as change of mRS at Day 90±3 compared with mRS at baseline.
The mRS is a 7-point scale from 0 to 6, with higher scores indicating worse outcome.
|
Baseline to Day 90 ± 3 days
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Xunming Ji, PhD, MD, Xuanwu Hospital, Beijing
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- PRO-STROKE
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .