Clinical trial NCT03775824: Faecal Analyses in Rheumatoid Arthritis Therapy
Official title: Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Keywords: microbiome
methotrexate
tnf-inhibitor
dysbiosis
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2018-12-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study encompasses consecutive patients with rheumatoid arthritis who by their physician at the Rheumatology Clinic, Skåne University Hospital, have been prescribed any of the predefined drugs.

Patients who are willing to comply with the study protocoll are included.

The study population is consequently not a sample, but encompasses a majority of patients being prescribed theses medications at our University clinic.

Brief summary: This study evaluates the intestinal microbiome and disease activity in patients with rheumatoid arthritis receiving immunosuppressive therapy. Patients will be analysed at two time points in reference to two predefined primary endpoints:

* Changes in intestinal microbiome
* Response to therapy

The investigators want to evaluate if successful treatment of rheumatoid arthritis coincide with specific changes in the gut flora.

Detailed description: Methotrexate (MTX) and tumor necrosis factor (TNF) -inhibitors are two efficient medications for the treatment of rheumatoid arthritis. In a substantial number of cases however, these medications remain ineffective. At present, the scientific community has limited understanding of why some patients are resistant to these medications. The purpose of this study is to understand if the gut flora may associate with treatment response.

Recent studies have associated rheumatoid arthritis with intestinal dysbiosis. Specifically, the bacteria Prevotella copri, has been associated with this disease, an observation that has been supported also by mechanistic studies. In patients receiving methotrexate, normalization of dysbiosis has been associated with successful treatment.

This study is of observational character and integrated in the routine clinical care of patients with rheumatoid arthritis at the Rheumatology Clinic, Skane University Hospital, Lund, Sweden. Study participants are asked to deliver blood and fecal sampling at two time-points together with clinical evaluation of disease activity. With an estimated inclusion of 50 patients, at least 20 responders and 20 non-responders are expected to be included and to be compared to each other.

If successful treatment response in rheumatoid arthritis is associated with specific alterations of the gut flora, these results may guide future studies on the impact of dysbiosis and probiotics on this disease.

Eligibility criteria: Inclusion Criteria:

* Rheumatoid arthritis according to the 2010 classification criteria
* About to start methotrexate or TNF-inhibitor because of active disease

Exclusion Criteria:

* Failure to understand protocol
* A history of alcohol abuse
* Concomitant inflammatory bowel disease
* Any history of diverticulitis
* A history of failure to comply with prescribed medication
* Ongoing biological therapy

Primary outcomes:
measure: Intestinal gut flora in rheumatoid arthritis
timeFrame: Analysis made at study start/baseline
measure: Change in gut flora
timeFrame: Change from baseline Dysbiosis Index Score at 6 months
measure: Change in disease activity/treatment response at follow up
timeFrame: Change from baseline DAS-28 at 6 months
Secondary outcomes:
measure: Adherance to immunosuppressive therapy
timeFrame: Analysis made at 6 months follow up
measure: Change in intestinal concentration Prevotella
timeFrame: Change from baseline concentration at 6 months
measure: Change in intestinal concentration Lactobacillus
timeFrame: Change from baseline concentration at 6 months
measure: Change in intestinal concentration Clostridia
timeFrame: Change from baseline concentration at 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Skane University Hospital
name: Kristofer Andréasson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andreasson K, Alrawi Z, Persson A, Jonsson G, Marsal J. Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease. Arthritis Res Ther. 2016 Nov 29;18(1):278. doi: 10.1186/s13075-016-1182-z.
citation: Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, Wu X, Li J, Tang L, Li Y, Lan Z, Chen B, Li Y, Zhong H, Xie H, Jie Z, Chen W, Tang S, Xu X, Wang X, Cai X, Liu S, Xia Y, Li J, Qiao X, Al-Aama JY, Chen H, Wang L, Wu QJ, Zhang F, Zheng W, Li Y, Zhang M, Luo G, Xue W, Xiao L, Li J, Chen W, Xu X, Yin Y, Yang H, Wang J, Kristiansen K, Liu L, Li T, Huang Q, Li Y, Wang J. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015 Aug;21(8):895-905. doi: 10.1038/nm.3914. Epub 2015 Jul 27.
citation: Pianta A, Arvikar SL, Strle K, Drouin EE, Wang Q, Costello CE, Steere AC. Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints. J Clin Invest. 2017 Aug 1;127(8):2946-2956. doi: 10.1172/JCI93450. Epub 2017 Jun 26.