Microbial Dysbiosis in Rheumatoid Arthritis (MyRA)

Microbial Dysbiosis in the Pathogenesis of Rheumatoid Arthritis: Using Metagenomics to Predict Methotrexate Efficacy

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.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• United Kingdom
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospitals Nhs Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Early rheumatoid arthritis commencing methotrexate monotherapy

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in DAS28-CRP score	Disease Activity Score using 28 joints and C-reactive Protein	0-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SDAI score	Simplified Disease Activity Index	0-6 months
Concentration of CRP in blood	C-reactive Protein (an inflammatory biomarker)	0-6 months
ESR value (blood)	Erythrocyte Sedimentation Rate (an inflammatory biomarker)	0-6 months
Concentration of anti-CCP in blood	Anti-Cyclic Citrullinated peptide (disease-specific antibody)	0-6 months
Concentration of RF in blood	Rheumatoid Factor (disease-specific antibody)	0-6 months

Collaborators and Investigators

• Sponsor: Quadram Institute Bioscience
• Collaborators: Norfolk and Norwich University Hospitals NHS Foundation Trust; University of East Anglia; Action Arthritis
• Investigators: Study Chair: Simon Carding, Prof, Quadram Institute Bioscience

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2019
• Primary Completion (ANTICIPATED): April 30, 2021
• Study Completion (ANTICIPATED): July 30, 2021

Study Registration Dates

• First Submitted: January 10, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (ACTUAL): January 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; microbial dysbiosis; dietary factors
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Dysbiosis
• Other Study ID Numbers: QIB01/2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No