Clinical trial NCT03802890: Microbial Dysbiosis in Rheumatoid Arthritis
Official title: Microbial Dysbiosis in the Pathogenesis of Rheumatoid Arthritis: Using Metagenomics to Predict Methotrexate Efficacy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Keywords: microbial dysbiosis
rheumatoid arthritis
dietary factors
Lead sponsor: Quadram Institute Bioscience
Sponsor class: OTHER
Collaborators: name: Action Arthritis
name: University of East Anglia
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
First posted: 2019-01-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Early rheumatoid arthritis commencing methotrexate monotherapy

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in DAS28-CRP score
timeFrame: 0-6 months
Secondary outcomes:
measure: Change in SDAI score
timeFrame: 0-6 months
measure: Concentration of CRP in blood
timeFrame: 0-6 months
measure: ESR value (blood)
timeFrame: 0-6 months
measure: Concentration of anti-CCP in blood
timeFrame: 0-6 months
measure: Concentration of RF in blood
timeFrame: 0-6 months
Other outcomes:
Locations:
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
state: Norfolk
Study officials:
affiliation: Quadram Institute Bioscience
name: Simon Carding, Prof
role: STUDY_CHAIR
References: