Efficacy and Safety of Therapeutic Application of Clostridium Butyricum in Patiens With Stenosing Crohn's Disease: a Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Efficacy of C. butyricum in stimulating autophagy
研究概览
简要总结
Crohn's disease is a condition of unknown etiology with an immune-mediated pathogenesis. The subgroup of Crohn's disease with a stricturing phenotype represents a particular challenge for clinicians, as currently no effective medical therapies are available for the prevention or treatment of fibrosis. Autophagy is a key mechanism in the regulation of cellular homeostasis, and preliminary reports from our group and others have suggested a potential role in the pathogenesis of fibrostenotic complications in Crohn's disease.
The next-generation probiotic Clostridium butyricum has recently been proposed as a treatment option in several conditions, including inflammatory bowel diseases (IBD). Its beneficial effects are mainly exerted through the production of butyric acid, which in turn plays important roles at the intestinal mucosal level, including the stimulation of autophagy. The possibility of stimulating autophagy in patients with stricturing Crohn's disease may represent a promising therapeutic approach for the prevention and treatment of fibrosis.
This study involves the collection of biopsy and blood samples from 40 patients with stricturing Crohn's disease undergoing colonoscopy. In the two months preceding colonoscopy, patients will be randomized into four groups:
Patients treated with C. butyricum
Patients treated with the autophagy stimulator trehalose
Patients treated with C. butyricum + trehalose
Patients treated with placebo
Laboratory analyses will be performed on biopsy and blood samples to evaluate and quantify molecular mediators involved in inflammation, fibrosis, and autophagy.
详细描述
Crohn's disease is a chronic, relapsing inflammatory bowel disease with unknown etiology, involving immune dysregulation and microbiota alterations. Stricturing disease (Montreal B2 phenotype) represents a major unmet therapeutic need, as no pharmacological therapies are currently available for intestinal fibrosis, which is often managed surgically.
Autophagy, a key regulator of cellular homeostasis, has been linked to Crohn's disease pathogenesis, with genetic studies identifying polymorphisms in autophagy-related genes. Impaired autophagy may exacerbate inflammation, oxidative stress, and tissue damage. Preliminary data from our group show reduced autophagy in patients with stricturing Crohn's disease compared to those with inflammatory phenotype or healthy controls.
Clostridium butyricum, a next-generation probiotic with strong butyrate-producing activity, exerts anti-inflammatory and mucosal protective effects partly through stimulation of autophagy. Its use may represent a novel therapeutic approach to prevent or mitigate fibrostenotic complications in Crohn's disease.
This is a non-profit, interventional clinical pilot study enrolling 40 patients with stricturing Crohn's disease (B2, Montreal classification; localization L2 or L3). Patients undergoing clinically indicated colonoscopy will be randomized to one of four groups to receive for two months prior to the procedure:
- C. butyricum supplementation
- Trehalose supplementation (a known autophagy inducer)
- Combined C. butyricum + trehalose
- Placebo During colonoscopy, routine biopsies will be obtained, with two additional samples collected for research purposes, along with peripheral blood samples. Laboratory analyses will focus on molecular mediators of inflammation, fibrosis, oxidative stress, and autophagy pathways.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients with a confirmed diagnosis of Crohn's disease (established according to clinical, endoscopic, histological, and radiological criteria in line with current Italian and European guidelines), with a stricturing phenotype (B2 according to the Montreal classification), determined based on the patient's clinical history and instrumental examinations, with disease localized to the right colon or ileocecal region, followed at the Inflammatory Bowel Disease Outpatient Clinic of the Gastroenterology and Digestive Endoscopy Unit, in whom a colonoscopy with biopsies has been scheduled for clinical indication (disease reassessment, flare-up, or follow-up).
- •Patients aged ≥18 and ≤85 years.
- •Patients either not receiving any specific immunomodulatory therapy for Crohn's disease or undergoing treatment with mesalazine or sulfasalazine.
- •Patients who have been adequately informed about the study protocol and who have understood and voluntarily signed the informed consent form.
排除标准
- •Other acute or chronic inflammatory bowel diseases (e.g., diverticulitis, infectious colitis, ulcerative colitis).
- •Patients receiving treatment for Crohn's disease with immunosuppressive drugs (thiopurines, methotrexate, cyclosporine), biologics (anti-TNFα, vedolizumab, ustekinumab), oral antiJAK or oral/intravenous corticosteroids.
- •Immunological or rheumatologic diseases.
- •Current or past malignancies.
- •Active infections.
- •History of organ transplantation.
- •Current treatments with pharmacological agents known to significantly modulate the autophagic process.
研究组 & 干预措施
C. butyricum
Clostridium butyricum CBM 588 (27 x 10^5 CFU/day)
干预措施: Clostridum Butyricum Capsule (Dietary Supplement)
Trehalose
Threhalose (30g/day)
干预措施: Trehalose (Dietary Supplement)
C butyricum + trehalose
C. butyricum (27 x 10^5 CFU/day) + trehalose (30 g/day)
干预措施: Clostridum Butyricum Capsule (Dietary Supplement)
placebo
Patients with no treatment
C butyricum + trehalose
C. butyricum (27 x 10^5 CFU/day) + trehalose (30 g/day)
干预措施: Trehalose (Dietary Supplement)
结局指标
主要结局
Efficacy of C. butyricum in stimulating autophagy
时间窗: 2 months
We evaluate the stimulation of autophagy measuring the mucosal expression and production of the molecular markers LC3 b II and p62 after treatment with C. butyricum
Safety of administration of C. butyricum
时间窗: 2 months
Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] of C. butyricum in Crohn's disease patients will be evaluated by adverse event monitoring and reporting
次要结局
- Treatment effect comparison(2 months)
- Oxydative stress measurement and comparation(2 months)
研究者
Cristiano Pagnini
MD, PhD
San Giovanni Addolorata Hospital