Manipulation of the Enteral Microbiome by Fecal Microbiota Transplantation Among Adult Patients With Malignant Hematological Diseases
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Disease activity
研究概览
简要总结
In Hungary - in comparison to other member states of the European Union - about 75000 new cases of cancer are diagnosed annually, from which approximately 4500-5000 patients suffer from so-called malignant hematological diseases. This disease group includes various leukemias (blood cancers) and lymphomas (lymph node cancers). Chemotherapy for patients with malignant hematological diseases is particularly difficult to bear, as it affects the entire body, including the "good" gut bacteria living inside, and recovery can take several years. Due to the decrease of the "good" gut bacteria during treatment, patients are more prone to acquiring various difficult-to-treat infections, which can lead to deterioration of quality of life, prolonged hospitalization, and in the worst cases, death. The method outlined in this research plan is called fecal microbiota transplantation, during which stool from a healthy person is introduced into the body of the sick patient. The "good" gut bacteria present in the stool then restore the patient's entire gut flora (the process is somewhat similar to the use of probiotics available on the market, but it is a much more effective method). This research aims to assess the success of fecal microbiota transplantation in adults with malignant hematological diseases over a long-term follow-up period, thus contributing to the restoration of their acceptable quality of life.
详细描述
Fecal microbiota transplantation (FMT) is currently a widely accepted method of manipulating enteric microbiome, and is an internationally recommended procedure in the treatment for Clostridioides (formerly Clostridium) difficile (C. difficile) infection. The goal of FMT is to restore physiological gut microbiome through natural competition, by administering a stool graft harvested from a healthy person. FMT not only eliminates C. difficile-induced colitis, but also colonization of multidrug-resistant bacterial/fungal species, and certain types of intestinal epithelial damage occuring in some medical conditions. In recent years due to pleiotropic effects of FMT, scientific interest has turned towards adult patients with malignant hematological diseases, since all of the pathological conditions mentioned earlier occur during clinical care in this population, due to detrimental effects of immuno-chemotherapy. Based on promising preliminary results, FMT could be a successful, easily implementable intervention for these patients in the future.
Therefore, the aim of this study is to perform FMTs in four indication groups among adult patients with malignant hematological diseases treated at South Pest Central Hospital - National Institute of Hematology and Infectious Diseases (Budapest, Hungary), followed by a 180-day follow-up period, during which standardized clinical, laboratory, imaging, and microbiological data are collected. In addition, a high-resolution microbiome analys to monitor microbiological changes of recipient pre-/post-FMT blood and stool samples is planned, in collaboration with Departmental Group of Infectious Diseases and Institute of Medical Microbiology of Semmelweis University (Budapest, Hungary).
This study aims to assess both the bacterial and fungal components of the enteric microbiome in adult patients receiving routine clinical care for malignant hematological diseases, and to explore the potential of manipulating the microbiome through fecal microbiota transplantation (FMT). The hypothesis is that microbiome manipulation with FMT in these patients may induce a successful and sustained response by restoring the physiological intestinal microbiome, a premise that this long-term, comprehensive clinical and microbiological follow-up study seeks to support.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (diagnosis age ≥18 years) with malignant hematological disease treated at our center, and
- •Capable of giving written informed consent after decision-making, and
- •Documented patient colonization with MDR bacterial or fungal isolates, or
- •Active C. difficile infection, or
- •Patient has undergone autologous or allogeneic hematopoietic stem cell transplantation, or
- •Ongoing corticosteroid-refractory acute gastrointestinal GvHD.
排除标准
- •(one or more must be met):
- •Active bacterial or fungal bloodstream infection requiring antimicrobial therapy, or
- •Peripheral blood absolute neutrophil count <0.5 G/l on ≥7 consecutive days before planned FMT with maximum dose of administered G-CSF, or
- •Pressor-refractory septic shock, or
- •Major gastrointestinal bleeding within 7 consecutive days before planned FMT, or
- •Any pathological process inhibiting successful or safe nasogastric tube insertion, or
- •Lack of written informed consent.
研究组 & 干预措施
FMT
Patients receiving fecal microbiota transplantation (FMT) for different clinical reasons
干预措施: Fecal Microbial Transplantation (Biological)
non-FMT
Patients not receiving fecal microbiota transplantation (FMT)
结局指标
主要结局
Disease activity
时间窗: On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls
Disease activity: hematological remission vs. relapse, GvHD activity. Disease activity of the malignant hematological underlying disease (hematological remission vs. relapse) is defined according to the published methodological recommendations by the National Comprehensive Cancer Network and the European Hematology Association (or the American Society of Hematology, if neither has specific guidance), specifically for each disease. GvHD activity is defined according to the published methodological recommendations of the European Bone Marrow Transplantation Society.
次要结局
- Reducibility of applied immunosuppressive pharmacotherapy(On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls)
- Reducibility of applied antimicrobial pharmacotherapy(On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls)
- Survival(On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared controls)
- Clinical cure of C. difficile infection(On Day 7, Day 30, Day 60 and Day 180, since the intervention, compared to baseline and controls)
研究者
Bálint Gergely Szabó
M.D. Ph.D.
Del-Pest Central Hospital - National Institute of Hematology and Infectious Diseases