Efficacy and Safety of Faecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate: a 24-week, Double-Blind, Randomised Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- The American College of Rheumatology 20 (ACR20) response at 16 weeks
研究概览
简要总结
In this 24-week, single center, randomized, double-blind study, the investigators will evaluate the efficacy and safety of fecal microbiota transplantation in patients with active rheumatoid arthritis refractory to methotrexate
详细描述
Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by painful synovium inflammation, bony erosions, immune activation. Gut microbiota plays an important role in pathophysiology of RA. FMT(fecal microbiota transplantation) is the engraftment of microbiota from a healthy donor into a recipient to achieve restoration of the normal gut microbial community structure.This study evaluates the efficacy and safety of FMT with methotrexate in patients with active RA refractory to methotrexate
Objectives:
- To evaluate the efficacy of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX.
- To evaluate the safety of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX DESIGN
This is a Phase 2, randomized, 24-week, double-blind, parallel group study, and 30 patients with active RA refractory to MTX will be randomized in a 1:1 ratio to one of the following 2 parallel treatment arms:
- FMT from healthy donor plus methotrexate
- autologous FMT(from the participant himself/herself) plus methotrexate
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years with informed consent
- •Fulfill the 2010 ACR/EULAR classification criteria for rheumatoid arthritis
- •Positive RF or anti-CCP antibody on screening
- •Have active RA shown by swollen joint count(SJC)≥4 and tender joint count(TJC)≥4 and ESR >28 mm/hr or C-reactive protein > 1.5 ULN
- •Have received methotrexate for 3 months or longer and at a stable dose of 7.5 to 25 mg/week (extremes included) for at least four weeks prior to screening and willing to continue on this regimen for the duration of the study.
- •Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA
- •If taking oral steroids, these should be at a dose ≤10 mg/day of prednisone or prednisone equivalent and stable for at least four weeks prior to screening;
- •If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least two weeks prior to screening;
- •Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses);
- •Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least four weeks after the last dose of study drug. Sexually active men must agree to use a medically acceptable form of contraception during the study and continue its use for at least 3 months after the last dose of study drug; and
- •Willing to suspend the use of other adjuvant treatment for the duration of the study including acupuncture, massage, etc.
排除标准
- •Pregnant, lactating or further fertility requirements
- •History of any inflammatory rheumatological disorders other than RA;
- •Previously received any biologic agents.
- •Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background methotrexate;
- •Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
- •Active or chronic infection, including HIV, HCV, HBV, tuberculosis.
- •Malignancy or history of malignancy.
- •Severe, progressive, or uncontrolled cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease
- •unable to undergo colonoscopy.
研究组 & 干预措施
FMT+MTX
FMT One FMT is performed at baseline by gastroscopic guidance. The same FMT is repeated 4 weeks later. The transplant consists of 50 g mixed feces obtained from 3-5 non-related healthy donors. The donor feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the recipient.
Drug: Methotrexate (MTX) Weekly methotrexate
干预措施: FMT+MTX (Procedure)
autologous FMT+MTX
autologous FMT (the feces used in FMT is from participant themselves) One identical FMT is performed at baseline using gastroscopic guidance and is repeated 4 weeks later. The corresponding participant's feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the participant himself or herself.
Drug: Methotrexate (MTX) Weekly methotrexate
干预措施: FMT+MTX (Procedure)
结局指标
主要结局
The American College of Rheumatology 20 (ACR20) response at 16 weeks
时间窗: week 16
The difference of ACR20 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)
次要结局
- The Disease Activity Score-28 (DAS28) response at 24 weeks(week 24)
- The European League Against Rheumatism (EULAR) response at 16 weeks(week 16)
- Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks(week 16)
- The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks(week 16)
- The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks(week 24)
- Incidence of adverse events and sever adverse events (SAE) during the study(week 24)
- The Disease Activity Score-28 (DAS28) response at 16 weeks(week 16)
研究者
Xuan Zhang
Professor
Peking Union Medical College Hospital