Fecal Microbiota Transplantation in Patients With Recurrent Clostridioides Cifficile Infection and Ulcerative Colitis: Single Infusion Versus Sequential Approach
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Number of UC patients who will obtain the eradication of rCDI 8 weeks after treatments (single FMT vs sequential FMT)
研究概览
简要总结
Clostridioides difficile infection (CDI) is the most frequent cause of infectious diarrhea in hospitalized patients and is responsible for 20-30 % of antibiotic-associated diarrhea cases. Inflammatory bowel diseases (IBD) are associated with an higher prevalence, recurrence and severity of CDI. The prevalence of recurrent CDI in patients with IBD is 2.5 to 8 times higher than in the general population, with a cumulative lifetime risk of 10 %. The higher risk to the development of CDI in patient with IBD is directly related to the microbiome alterations that are associated with this chronic disoder. Moreover, the use of antibiotics to cure CDI further worsens the gut microbiota, triggering potentially a self-maintaining cycle and predisposes such patients to a higher risk of recurrence. In these patients, CD superinfection is associated, with an increased rate of hospitalization, length of stay, the need to modify the treatment to the underlying disease, the increase rate of colectomy, there higher mortality rate, with a net increase of health costs.
Nowadays, as emerged by several studies FMT has been established as a valid treatment option against recurrent CDI (rCDI), and it is recommended by international guidelines.
Unfortunately, most FMT studies for rCDI have excluded patients with IBD. Recent evidence suggests that FMT is effective in patients with ulcerative colitis (UC) and concomitant rCDI, both in the treatment of the infection and in the improve of disease activity. To date, most studies evaluated the efficacy of single infusion of FMT in these patients.
Preliminary data from our group suggest that a sequential approach (i.e., repeated fecal infusions) may increase the efficacy of FMT in this population. Indeed, in 18 patients with IBD, single infusion fecal resulted in eradication of rCDI in 60% of cases, whereas this outcome was achieved in 89% of cases using a sequential approach. Similar data have been demonstrated in a retrospective study by Fischer and colleagues. However, more studies are advocated to confirm these results.
Therefore, our study aim to compare the efficacy of single FMT vs. sequential in the eradication of rCDI in patients with UC.
详细描述
Clostridioides difficile infection (CDI) is the most frequent cause of infectious diarrhea in hospitalized patients and is responsible for 20-30 % of antibiotic-associated diarrhea cases. Inflammatory bowel diseases (IBD) are associated with an higher prevalence, recurrence and severity of CDI. The prevalence of recurrent CDI in patients with IBD is 2.5 to 8 times higher than in the general population, with a cumulative lifetime risk of 10 %. The higher risk to the development of CDI in patient with IBD is directly related to the microbiome alterations that are associated with this chronic disoder. Moreover, the use of antibiotics to cure CDI further worsens the gut microbiota, triggering potentially a self-maintaining cycle and predisposes such patients to a higher risk of recurrence. In these patients, CD superinfection is associated, with an increased rate of hospitalization, length of stay, the need to modify the treatment to the underlying disease, the increase rate of colectomy, there higher mortality rate, with a net increase of health costs.
Nowadays, as emerged by several studies FMT has been established as a valid treatment option against recurrent CDI (rCDI), and it is recommended by international guidelines.
Unfortunately, most FMT studies for rCDI have excluded patients with IBD. Recent evidence suggests that FMT is effective in patients with ulcerative colitis (UC) and concomitant rCDI, both in the treatment of the infection and in the improve of disease activity. To date, most studies evaluated the efficacy of single infusion of FMT in these patients.
Preliminary data from our group suggest that a sequential approach (i.e., repeated fecal infusions) may increase the efficacy of FMT in this population. Indeed, in 18 patients with IBD, single infusion fecal resulted in eradication of rCDI in 60% of cases, whereas this outcome was achieved in 89% of cases using a sequential approach. Similar data have been demonstrated in a retrospective study by Fischer and colleagues. However, more studies are advocated to confirm these results.
Therefore, our study aim to compare the efficacy of single FMT vs. sequential in the eradication of rCDI in patients with UC.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years;
- •Active UC (partial Mayo score ≥2);
- •Relapsing infection of C. difficile;
- •Ability to express consent for inclusion in the study.
- •Indication, in the clinical practice setting, for fecal microbiota transplantation from a healthy donor for recurrent CDI
排除标准
- •Age < 18 years;
- •Other gastrointestinal infections, excluding C. difficile;
- •Known gastrointestinal diseases, other than UC, in active stage (e.g., infectious gastroenteritis, celiac disease, irritable bowel syndrome, chronic pancreatitis, bile acid diarrhea, etc.);
- •Previous colon surgery or skin ostomy packing;
- •Food allergies;
- •Current or recent (<2 weeks) therapy with drugs that may alter the microbiota (e.g., systemic antimicrobials, probiotics, proton pump inhibitors, immunosuppressants, metformin), except antibiotics against C. difficile;
- •Heart failure or heart disease with FE ≤ 30 %;
- •Severe respiratory failure;
- •Psychiatric disorders;
- •Pregnancy and lactation;
- •Inability to provide informed consent.
研究组 & 干预措施
. Single FMT
Patients enrolled in this arm will receive a single infusion of donor FMT
干预措施: single FMT (Biological)
Sequential FMT
Patients enrolled in this arm will receive sequential infusions of donor FMT
干预措施: sequential FMT (Biological)
结局指标
主要结局
Number of UC patients who will obtain the eradication of rCDI 8 weeks after treatments (single FMT vs sequential FMT)
时间窗: 2 months
The investigators will compare the number of participants who will obtain the eradication of rCDI (assessed by C. difficile toxin exam) 8 weeks after treatments (single FMT vs sequential FMT)
次要结局
- Evaluation of Ulcerative Colitis activity(2 months)
- Evaluation of changes in recipients' microbiome after treatments, at each time point.(2 months)
- Evaluation of the safety of the two treatments(2 months)
- Number of UC patients who will obtain the eradication of rCDI 1 - 4 weeks after treatments (single FMT vs sequential FMT)(1 months)
研究者
IANIRO GIANLUCA
Principal Investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS