Microbial Dysbiosis in the Pathogenesis of Rheumatoid Arthritis: Using Metagenomics to Predict Methotrexate Efficacy
试验速览
- 阶段
- 不适用
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in DAS28-CRP score
研究概览
简要总结
The MyRA study will primarily investigate whether there are associations between the structure and function of the gut microbiome and response to methotrexate in early rheumatoid arthritis patients. The microbiome will be characterised via shotgun metagenomic sequencing of microbial DNA present in stool samples taken during the participant's first 6 months of taking methotrexate.
详细描述
Methotrexate is often the first drug of choice for patients with early rheumatoid arthritis (RA), but its efficacy is highly variable and it can lead to severe side effects. There are currently no reliable predictors of methotrexate efficacy for people with early RA.
Microbial dysbiosis (an imbalanced microbiome) has recently been implicated in RA, with associations between specific microbes and RA biomarkers or disease activity. Gut microbes have extensive capabilities in terms of xenobiotic (e.g. drug) metabolism. Several gut microbes are able to alter the drug methotrexate in vitro, and it is possible this could effect drug efficacy in vivo. Alternatively methotrexate efficacy could be affected by baseline microbial composition or alterations to microbial composition over the course of treatment.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-65 years of age
- •RA diagnosis based on ACR 2010 classification criteria with symptoms starting within the last 2 years
- •Referred by GP to the Early Arthritis Clinic at the Norfolk and Norwich University Hospitals NHS trust
- •Commencing methotrexate monotherapy for the first time
排除标准
- •Initially commencing combination therapy (prior to first stool sample) rather than methotrexate monotherapy i.e. MTX combined with another DMARD or prednisolone
- •Commencement of MTX therapy prior to first stool sample or cessation of MTX therapy at any point during the study
- •History of psoriasis
- •Those currently suffering from, or have ever suffered from, any diagnosed gastrointestinal disease, gastrointestinal disorders including regular diarrhoea and constipation (excluding hiatus hernia unless symptomatic) and/or have undergone gastrointestinal surgery.
- •Those regularly (3+ times/week) taking self-prescribed over the counter medications for digestive/gastrointestinal conditions
- •Use of laxatives within 7 days prior to sampling unless these have been used on a regular basis (3+ times/week) for more than one month prior to the study and will continue to be used throughout the study period
- •The use of over-the-counter medications or food/drinks containing pre and/or probiotics within 7 days prior to sampling, unless these have been used on a regular basis (3+ times/week) for more than one month prior to the study and will continue to be used throughout the study period
- •Significant alteration of the participant's normal diet at any point during the study (e.g. adoption of the 5:2 fasting diet)
- •Regular (3+ times/week) or recent (within 3 months) use of colonic irrigation or other bowel cleansing techniques
- •Recently returned to the UK following a period abroad, and who have suffered gastric symptoms during the period abroad or on return to the UK. These will be assessed on an individual basis
- •Currently taking or finished a course of antibiotics within the last 3 months
- •Currently pregnant or lactating
- •Living with or related to any member of the Study Team
- •Those who have limited or no understanding of spoken and written English
结局指标
主要结局
Change in DAS28-CRP score
时间窗: 0-6 months
Disease Activity Score using 28 joints and C-reactive Protein
次要结局
- Concentration of CRP in blood(0-6 months)
- Concentration of RF in blood(0-6 months)
- Change in SDAI score(0-6 months)
- ESR value (blood)(0-6 months)
- Concentration of anti-CCP in blood(0-6 months)