Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Microbial Dysbiosis in Rheumatoid Arthritis (MyRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03802890
Recruitment Status : Enrolling by invitation
First Posted : January 14, 2019
Last Update Posted : June 18, 2020
Sponsor:
Collaborators:
Action Arthritis
University of East Anglia
Norfolk and Norwich University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
Quadram Institute Bioscience

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
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.

Layout table for study information
Study Type : Observational
Estimated 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 : February 1, 2019
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : July 30, 2021

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Change in DAS28-CRP score [ Time Frame: 0-6 months ]
    Disease Activity Score using 28 joints and C-reactive Protein


Secondary Outcome Measures :
  1. Change in SDAI score [ Time Frame: 0-6 months ]
    Simplified Disease Activity Index

  2. Concentration of CRP in blood [ Time Frame: 0-6 months ]
    C-reactive Protein (an inflammatory biomarker)

  3. ESR value (blood) [ Time Frame: 0-6 months ]
    Erythrocyte Sedimentation Rate (an inflammatory biomarker)

  4. Concentration of anti-CCP in blood [ Time Frame: 0-6 months ]
    Anti-Cyclic Citrullinated peptide (disease-specific antibody)

  5. Concentration of RF in blood [ Time Frame: 0-6 months ]
    Rheumatoid Factor (disease-specific antibody)


Biospecimen Retention:   Samples With DNA
  • faecal samples
  • blood samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Early rheumatoid arthritis commencing methotrexate monotherapy
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802890


Locations
Layout table for location information
United Kingdom
Norfolk and Norwich University Hospitals NHS Foundation Trust
Norwich, Norfolk, United Kingdom, NR4 7UY
Sponsors and Collaborators
Quadram Institute Bioscience
Action Arthritis
University of East Anglia
Norfolk and Norwich University Hospitals NHS Foundation Trust
Investigators
Layout table for investigator information
Study Chair: Simon Carding, Prof Quadram Institute Bioscience
  Study Documents (Full-Text)

Documents provided by Quadram Institute Bioscience:
Study Protocol  [PDF] October 8, 2018

Layout table for additonal information
Responsible Party: Quadram Institute Bioscience
ClinicalTrials.gov Identifier: NCT03802890    
Other Study ID Numbers: QIB01/2018
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Quadram Institute Bioscience:
microbial dysbiosis
rheumatoid arthritis
dietary factors
Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Dysbiosis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes