Studies of Treatment Effects, Host-Pathogen Responses, and Therapeutic Mechanisms in Clostridioides Difficile Infection
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Number of participants with sustained cure
研究概览
简要总结
The goal of this observational study is to learn how different treatments for Clostridioides difficile infection (CDI) work, and which biological mechanisms are involved in recovery. The study will compare standard antibiotic treatment and fecal microbiota transplantation (FMT).
The main questions it aims to answer are:
- How do antibiotic treatment and FMT affect treatment outcome in CDI?
- How does the gut microbiota change during and after treatment?
- Which microbial and metabolic factors are associated with recovery or treatment failure?
- How does treatment affect the intestinal barrier, immune response, and patient-reported quality of life?
Participants with CDI will receive treatment as part of routine clinical care, either antibiotics or FMT. Researchers will follow participants over time and collect biological samples to study treatment effects.
Participants will:
- Provide stool samples during the acute infection and during follow-up
- Have treatment outcomes assessed at 2 and 8 weeks
- Be followed for up to 5 years to study long-term effects
- Provide blood and urine samples during follow-up
- Provide nasal samples to study potential microbiota changes at distant body sites
- Complete questionnaires on symptoms and health-related quality of life
- In a subgroup, undergo repeated sigmoid biopsies to study intestinal mucosal healing
The results are expected to increase understanding of how FMT and antibiotics lead to recovery in CDI and may support improved and more targeted future treatments.
详细描述
Clostridioides difficile infection (CDI) is a frequent cause of antibiotic-associated colitis and is characterized by high rates of recurrence and, in some patients, refractory disease. Although fecal microbiota transplantation (FMT) is an effective treatment for recurrent and refractory CDI, the biological mechanisms underlying treatment response, early clinical improvement, long-term effects, and vulnerability to subsequent antibiotic exposure remain incompletely understood.
This is an observational study designed to characterize biological and clinical changes associated with standard antibiotic treatment and FMT in patients with CDI. The study will investigate intestinal microbiota composition, microbial metabolites, mucosal and systemic immune responses, intestinal barrier function, and patient-reported outcomes, and relate these findings to clinical disease course and treatment outcome.
Adult patients with symptomatic, microbiologically verified CDI receiving routine clinical care will be included. Treatment decisions, including the use of antibiotics or FMT, are made by the treating physician according to clinical guidelines and are not influenced by study participation. Participants will be followed longitudinally for up to five years.
Biological samples will be collected during the acute CDI episode and at predefined follow-up time points. Stool samples will be obtained to characterize intestinal microbiota composition and metabolic profiles over time. In participants treated with FMT, stool sampling will be more frequent during the first week after treatment to capture early post-treatment changes. Blood samples will be collected for assessment of systemic immune and inflammatory markers. Urine samples will be collected for analysis of metabolites related to intestinal barrier integrity. Nasopharyngeal swabs will be obtained to explore whether modulation of the intestinal microbiota is associated with changes in microbiota composition and immune responses at distant mucosal sites.
In a subgroup of participants deemed suitable by the responsible clinician, repeated lower colonic biopsies will be obtained using sigmoidoscopy. These samples will be used to assess colonic mucosal healing, mucus barrier function, mucosa-associated microbiota, and local immune responses.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 years or older
- •Symptomatic, microbiologically verified Clostridioides difficile infection
- •Receiving inpatient or outpatient care at Umeå University Hospital
- •Able and willing to provide written informed consent
- •Willing to participate in protocol-driven follow-up for up to 5 years
排除标准
- •Age below 18 years
- •Inability to provide written informed consent
研究组 & 干预措施
Antibiotic treatment
Participants with Clostridioides difficile infection receiving standard antibiotic treatment as part of routine clinical care.
干预措施: Antibiotic treatment (Other)
Fecal microbiota transplantation (FMT)
Participants with Clostridioides difficile infection receiving fecal microbiota transplantation as part of routine clinical care.
干预措施: Fecal microbiota transplantation (FMT) (Other)
结局指标
主要结局
Number of participants with sustained cure
时间窗: At follow-up 8 weeks after initiation of the current CDI treatment.
Number of participants with sustained cure, defined as resolution of Clostridioides difficile infection symptoms after completion of the current treatment course and no recurrence during the 8-week follow-up period.
次要结局
- Number of participants with CDI recurrence(At follow-up 8 weeks after initiation of the current CDI treatment)
- Intestinal microbiota diversity(Baseline and longitudinal follow-up up to 5 years)
- Stool short-chain fatty acid concentrations(Baseline and longitudinal follow-up up to 5 years)
- Colonic mucus barrier function(Baseline and follow-up assessments up to approximately 8 weeks after initiation of the current CDI treatment)
- Circulating markers of intestinal barrier function(Baseline and longitudinal follow-up up to 5 years)
- Health-related quality of life(Baseline and longitudinal follow-up up to 5 years)
- Number of participants with new Clostridioides difficile infection episodes after subsequent antibiotic exposure(From 8 weeks after initiation of the current CDI treatment and up to 5 years)