Placebo-Controlled, Double-Blind, Phase 2 Trial of Probiotic Supplementation in Acute Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 主要终点
- Beta diversity of gut microbiota at Day 90±3 (treatment vs. placebo)
研究概览
简要总结
The primary objective of this study is to evaluate the effect of daily oral administration of the probiotic supplement OMNi-BiOTiC® SR-9 for 90 days, compared to placebo, on gut microbiome beta diversity in patients aged 60 years or older with acute ischemic stroke.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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;
研究组 & 干预措施
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.
干预措施: probiotic supplement OMNi-BiOTiC® SR-9 (Dietary Supplement)
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.
干预措施: Matching Placebo (Other)
结局指标
主要结局
Beta diversity of gut microbiota at Day 90±3 (treatment vs. placebo)
时间窗: 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.
次要结局
- Modified Rankin Scale (mRS) score at Day 90±3(Day 90 ± 3 days)
- Changes in gut microbiota diversity and relative abundance of Prevotella copri at Day 90±3(Baseline to Day 90 ± 3 days)
- Serum concentrations of short-chain fatty acids (SCFAs) at Day 90±3(Baseline and Day 90 ± 3 days)
- EQ-5D-5L at day 90(Day 90 ± 3 days)
- Barthel Index at day 90(Day 90 ± 3 days)
- Safety Outcomes(Baseline to Day 90 ± 3 days)
- Change in modified Rankin Scale (mRS) score from baseline to Day 90±3(Baseline to Day 90 ± 3 days)
研究者
Ji Xunming,MD,PhD
Principal Investigator
Capital Medical University