MyRA: Microbial Dysbiosis in Rheumatoid Arthritis

Sponsor

Quadram Institute Bioscience (Other)

Overall Status

Unknown status

CT.gov ID

NCT03802890

Collaborator

Action Arthritis (Other), University of East Anglia (Other), Norfolk and Norwich University Hospitals NHS Foundation Trust (Other)

Enrollment

Location

29.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Feb 1, 2019

Anticipated Primary Completion Date :

Apr 30, 2021

Anticipated Study Completion Date :

Jul 30, 2021

Outcome Measures

Primary Outcome Measures

Change in DAS28-CRP score [0-6 months]
Disease Activity Score using 28 joints and C-reactive Protein

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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