Allogeneic Fecal Microbiota Transplantation as a Consolidation Treatment After Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis
研究概览
简要总结
The hypothesis of the study is that according to modern data, the pathogenesis of multiple sclerosis is inextricably linked to the patient's microbiota. Therefore, transplantation of a normal fecal microbiota (FMT) can improve the outcome of autologous hematopoietic stem cell transplantation (autoHSCT) by increasing the disease-free period and disease progression suspension for at least 5 years after transplantation, which meets the NEDA (No Evidence of Disease Activity) criteria, satisfying the current trends of clinical neurology.
详细描述
AutoHSCT may be a method of choice to treat patients with refractory forms of multiple sclerosis, taking into account the insufficient efficacy of first line therapy, lack of availability (government approval) and high cost of monoclonal antibodies as a second line drugs. In this setting, according to the safety-efficiency ratio the most appropriate are reduced intensity conditioning regimens in autoHSCT. In 75% of cases for refractory forms of multiple sclerosis it is possible to achieve 5 years remission with transplant mortality less than 1%. In recent years, it is quite clear that gut microbiota abnormalities may be one of mechanisms for autoimmune diseases development. Therefore, the correction of gut dysbiosis through FMT from a healthy donor can improve the effectiveness of basic therapies. Currently, FMT is a rapidly developing method of treating intestinal infections associated with multi-resistant bacteria, based on the replacement of the recipient's microbiota by the donor's microbiota.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Multiple sclerosis (Relapsing-Remitting, Secondary-Progressive, Primary-Progressive)
- •Signed informed consent
- •No second tumors
- •No severe concurrent illness
- •1.0-6.5 points by EDSS
- •Disease duration less than 20 years
- •Disease progression on 1 and/or 2 line therapy (1 point EDSS 1.0-6.0 and 0,5 point EDSS 6.0-6.5)
排除标准
- •Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- •Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- •Respiratory distress >grade I
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- •Creatinine clearance < 60 mL/min
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <30%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
结局指标
主要结局
To evaluate effectiveness of autoHSCT in combination with FMT in patients with refractory multiple sclerosis
时间窗: 365 days
Multiple sclerosis progression free survival
次要结局
- To evaluate overall survival after autoHSCT in combination with FMT in patients with refractory multiple sclerosis(365 days)
- Quality of life status 1(365 days)
- Impact of autoHSCT on brain structure anatomy(365)
- To evaluate adverse effects after FMT in immunocompromised patients(365 days)
- Quality of life status 2(365 days)
- Evaluation of Immune system reconstitution after autoHSCT 1(365 days)
- Evaluation of Immune system reconstitution after autoHSCT 2(365 days)
研究者
Ivan S Moiseev
Deputy Director for research, Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation
St. Petersburg State Pavlov Medical University