Donor Versus Autologous Fecal Microbiota Transplantation for Axial Spondyloarthritis: a Double Blind, Placebo-Controlled, Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 99
- 试验地点
- 2
- 主要终点
- Minimal Clinically Important Improvement
研究概览
简要总结
Although biologic therapy have revolutionized the treatment of Spondyloarthrtitis (SpA), many patients do not experience complete relief of SpA related complaints.
It has been established that patients with SpA have an altered composition of microorganisms (microbiota) in the gut compared to healthy controls, and that this correlates to disease activity and respons to therapy.
The goal of this randomized double-blind study is to evaluate the efficacy of fecal microbiota transplantation (FMT) in patients with axial SpA with a suboptimal effect of biologic therapy.
The main questions it aims to answer are:
- Can FMT reduce disease activity in axial SpA?
- Can FMT alleviate pain and reduce fatigue in axial SpA?
- Is the composition of microorganisms restored to normal in patients with SpA after a treatment with FMT?
Participants will receive a single treatment in the form of an enema with either donor FMT or placebo at baseline. The primary endpoint will be evaluated after 90 days, but efficacy and safety will be monitored from baseline until 365 days.
详细描述
Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints (SIJ) and the spine.
The approach to treatment of axSpA is a combination of patient education, with a focus on exercise and lifestyle, and a medical treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line medical treatment, providing symptom relief for a large portion of the patients. For patients with inadequate response, or intolerance, to NSAIDs, biological (TNFi and IL17i) or targeted synthetic (JAKi) disease modifying drugs (b/ts-DMARDs) are considered a second-line treatment option and provide excellent efficacy for many patients. However, a substantial portion of the patients experience active disease despite this second-line therapy.
The cause of the disease is multifactorial, and both genetic and environmental factors contribute in the pathogenesis. Patients with axSpA have a higher prevalence of inflammatory bowel disease (IBD) than the background population, i.e. Crohn's disease and ulcerative colitis. However, inflammation in the gut is also demonstrated in 50-70% of patients without symptoms of IBD, and this inflammation is believed to be of importance in the development of the disease.
The human gut microbiota is the collection of microbes in the intestines. The composition of the microbiota is the result of many factors and have evolved over time to form a mutually beneficial relationship to both humans and microorganisms. Normally there is a balance and a stability in this composition, but in many conditions an imbalance, termed dysbiosis, has been demonstrated. This is also the case in axSpA, and the extent of this dysbiosis also relates to disease activity and to response to therapy.
Fecal microbiota transplantation (FMT) is a method used to alter the microbiota composition by transferring microbes from a healthy individual to a recipient. In several conditions this has both proven the ability to alter the microbiota and to provide symptom relief , e.g. clostridium difficile infections, ulcerative colitis and irritable bowel syndrome.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A person will be responsible for the Randomization and Allocation (RAP) procedure, and will be the only person not blinded to randomization and treatment. This person will, however, be blinded for the patient´s identity.
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
- •Axial Spondyloarthritis according to the ASAS classification criteria
- •Active disease defined as ASDAS ≥2.1 with elevated CRP ≥3 OR active inflammation on MRI within the last 3 months
- •Onset of axial SpA within last 10 years
- •Unsatisfactory relief of NSAIDs
- •On stable immunomodulatory treatment (TNFi, IL17i or JAKi) the last 3 months OR without immunomodulatory treatment last 3 months
排除标准
- •Planned dose adjustment or change in immunomodulatory treatment the next 90 days
- •Disease or disorder with life expectancy of ≤5 years
- •Severe immune deficiency (acquired, congenital og du to medication)
- •Previous treatment with FMT
- •Regular use of opioids with the exception of codeine and tramadol
- •Any specific diagnosis that could explain or contribute to the patients back pain (e.g. tumor, fracture, infection or degenerative disease)
- •Inflammatory spinal disease other than axSpA
- •Severe psychiatric disorder, alcohol- or drug abuse
- •Active inflammatory bowel disease
- •Microscopic colitis, diverticulitis or ileus
- •Active psoriasis
- •Fibromyalgia
- •Abdominal surgery excluding appendectomy, cholecystectomy, hysterectomy, caesarian section, sapling-ooforectomy and hernia surgery
- •Malignant disease excluding basalioma and melanoma stage 1
- •Conditions with expected necessary treatment with antibiotics during the study period, e.g. periodontitis end ischemic digital ulcers
- •Treatment with antibiotics 12 weeks prior to study entry
- •Pregnancy, lactation or planned pregnancy within the next 3 months
- •Contraindications for rectal catheter insertion
- •Planned rehabilitation program the next 90 days
- •Limited ability to comply with protocol requirements, including biobank participation
研究组 & 干预措施
Placebo/autologous FMT
Placebo treatment will be processed identically to active treatment, but with paritcipants own stool. The patients in the placebo group will consequently receive an enema with 60g of their own feces combined with glycerol and saline as a single treatment at baseline.
干预措施: Placebo (Drug)
Donor A FMT
Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.
干预措施: FMT (Drug)
Donor B FMT
Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.
干预措施: FMT (Drug)
Donor C FMT
Active treatment contain 60g of feces from a single healthy, screened donor. The feces is combined with glycerol and saline to a total volume of 440 ml in an enema bag. Each participant will only receive a single treatment at baseline.
干预措施: FMT (Drug)
结局指标
主要结局
Minimal Clinically Important Improvement
时间窗: 90 days
Proportion of patients that meet the criteria of Minimal Clinically Important Improvement in the donor FMT (dFMT) versus the autologous FMT (aFMT) group at day 90 after treatment (FMT - Fecal Microbiota Transplantation). Minimal Clinically Important Improvement is defined by a decrease of ≥1,1 in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score).
次要结局
- Adverse events(Day 0-90 and day 91-365)
- Bath Ankylosing Spondylitis Disease Activity Index(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Bath Anykylosing Spondylitis Funtional Index(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Patient global assessment(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- VAS spinal pain(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Maastricht Ankylosing Spondylitis Enthesitis Score(baseline and day 90)
- Modified Fatigue Impact Scale(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Ankylosing Spondylitis Disease Activity Score (ASDAS)20(baseline, day 30, day 60 and day 90)
- Bath Ankylosing Spondylitis Metrology Index(baseline and day 90)
- Ankylosing Spondylitis Disease Activity Score (ASDAS)40(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- RAND-36(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- The 66/68 Joint Count Score(baseline and day 90)
- Assessment in Spondyloarthritis International Society (ASAS)20(baseline, day 30, day 60 and day 90)
- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, 0-10)(baseline, day 30, day 60 and day 90)
- Bath Ankylosing Spondylitis Funtional Index (BASFI, 0-10)(baseline, day 30, day 60 and day 90)
- Patient global assessment of disease (PGA, 0-10)(baseline, day 30, day 60 and day 90)
- VAS spinal pain (Visual Analogue Scale, 0-10)(baseline, day 30, day 60 and day 90)
- Modified Fatigue Impact Scale (0-84)(baseline and day 90)
- RAND-36 (Quality-of-life measure)(baseline and day 90)
- Maastricht Ankylosing Spondylitis Enthesitis Score (MASES, 0-13)(baseline and day 90)
- Bath Ankylosing Spondylitis Metrology Index (BASMI)(baseline and day 90)
- Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, 0-10)(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Bath Anykylosing Spondylitis Funtional Index (BASFI, 0-10)(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Patient global assessment (PGA, 0-10)(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- VAS spinal pain (0-10)(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
- Modified Fatigue Impact Scale (0-84)(baseline and day 30, day 60, day 90, day 180, day 270 and day 365)
研究者
Gunnstein Bakland
Ass. Professor
University Hospital of North Norway