Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Region Skane
- 入组人数
- 50
- 主要终点
- Intestinal gut flora in rheumatoid arthritis
研究概览
简要总结
This study evaluates the intestinal microbiome and disease activity in patients with rheumatoid arthritis receiving immunosuppressive therapy. Patients will be analysed at two time points in reference to two predefined primary endpoints:
- Changes in intestinal microbiome
- Response to therapy
The investigators want to evaluate if successful treatment of rheumatoid arthritis coincide with specific changes in the gut flora.
详细描述
Methotrexate (MTX) and tumor necrosis factor (TNF) -inhibitors are two efficient medications for the treatment of rheumatoid arthritis. In a substantial number of cases however, these medications remain ineffective. At present, the scientific community has limited understanding of why some patients are resistant to these medications. The purpose of this study is to understand if the gut flora may associate with treatment response.
Recent studies have associated rheumatoid arthritis with intestinal dysbiosis. Specifically, the bacteria Prevotella copri, has been associated with this disease, an observation that has been supported also by mechanistic studies. In patients receiving methotrexate, normalization of dysbiosis has been associated with successful treatment.
This study is of observational character and integrated in the routine clinical care of patients with rheumatoid arthritis at the Rheumatology Clinic, Skane University Hospital, Lund, Sweden. Study participants are asked to deliver blood and fecal sampling at two time-points together with clinical evaluation of disease activity. With an estimated inclusion of 50 patients, at least 20 responders and 20 non-responders are expected to be included and to be compared to each other.
If successful treatment response in rheumatoid arthritis is associated with specific alterations of the gut flora, these results may guide future studies on the impact of dysbiosis and probiotics on this disease.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Rheumatoid arthritis according to the 2010 classification criteria
- •About to start methotrexate or TNF-inhibitor because of active disease
排除标准
- •Failure to understand protocol
- •A history of alcohol abuse
- •Concomitant inflammatory bowel disease
- •Any history of diverticulitis
- •A history of failure to comply with prescribed medication
- •Ongoing biological therapy
研究组 & 干预措施
MTX start
Patients with active rheumatoid arthritis who are either naive to methotrexate, or have not used this medicine in the last year and who are about to start therapy with methotrexate i.v. or s.c.
干预措施: MTX start (Drug)
TNF start
Patients with active rheumatoid arthritis who are either naive to TNF-inhibitors, or have not used this medicine in the last year and who are about to start therapy with any of the following (biosimilars included); infliximab, adalimumab, etanercept, certolizumab or golimumab
干预措施: TNF start (Drug)
结局指标
主要结局
Intestinal gut flora in rheumatoid arthritis
时间窗: Analysis made at study start/baseline
Intestinal gut flora based on DNA-based microbial analysis of fecal samples
Change in gut flora
时间窗: Change from baseline Dysbiosis Index Score at 6 months
Change in Dysbiosis Index Score at follow up compared to baseline. The Dysbiosis Index Score measures degree of intestinal dysbiosis on a scale from 1 to 5, where 5 indicates dysbiosis. The Index has been extensively described at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029765/
Change in disease activity/treatment response at follow up
时间窗: Change from baseline DAS-28 at 6 months
Change in Disease Activity Score 28 (DAS-28), an established index of disease activity in rheumatoid arthritis between 0-10, where 10 equals maximum activity.
次要结局
- Adherance to immunosuppressive therapy(Analysis made at 6 months follow up)
- Change in intestinal concentration Prevotella(Change from baseline concentration at 6 months)
- Change in intestinal concentration Clostridia(Change from baseline concentration at 6 months)
- Change in intestinal concentration Lactobacillus(Change from baseline concentration at 6 months)