Faecal Analyses in Rheumatoid Arthritis Therapy

NCT ID: NCT03775824

Last Updated: 2019-09-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-08-01
• Study Completion Date: 2019-06-01

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.

Conditions

Rheumatoid Arthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

MTX start

Patients with active rheumatoid arthritis who are either naive to methotrexate, or have not used this medicine in the last year and who are about to start therapy with methotrexate i.v. or s.c.

MTX start

Intervention Type: DRUG

Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis

TNF start

Patients with active rheumatoid arthritis who are either naive to TNF-inhibitors, or have not used this medicine in the last year and who are about to start therapy with any of the following (biosimilars included); infliximab, adalimumab, etanercept, certolizumab or golimumab

TNF start

Intervention Type: DRUG

Patient prescribed TNF-inhibitor because of active rheumatoid arthritis

Interventions

MTX start

Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis

Intervention Type: DRUG

TNF start

Patient prescribed TNF-inhibitor because of active rheumatoid arthritis

Intervention Type: DRUG

Other Intervention Names

MTX; TNF

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Region Skane

OTHER

Sponsor Role: lead

Responsible Party

Kristofer Andreasson

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kristofer Andréasson, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Skane University Hospital

References

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.

Reference Type: BACKGROUND

PMID: 27894337 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26214836 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28650341 (View on PubMed)

Other Identifiers

FART1

Identifier Type: -

Identifier Source: org_study_id