Faecal Analyses in Rheumatoid Arthritis Therapy

Rheumatoid Arthritis Clinical Trial

— FART  

Official title:

Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03775824
• Other study ID #: FART1
• Status: Completed
• Start date: August 1, 2016
• Est. completion date: June 1, 2019

Study information

• Verified date: September 2019
• Source: Region Skane
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: June 1, 2019
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MTX start
Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis
• TNF start
Patient prescribed TNF-inhibitor because of active rheumatoid arthritis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Region Skane

References & Publications (3)

Andréasson K, Alrawi Z, Persson A, Jönsson 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intestinal gut flora in rheumatoid arthritis	Intestinal gut flora based on DNA-based microbial analysis of fecal samples	Analysis made at study start/baseline
Primary	Change in gut flora	Change in Dysbiosis Index Score at follow up compared to baseline.; The Dysbiosis Index Score measures degree of intestinal dysbiosis on a scale from 1 to 5, where 5 indicates dysbiosis. The Index has been extensively described at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029765/	Change from baseline Dysbiosis Index Score at 6 months
Primary	Change in disease activity/treatment response at follow up	Change in Disease Activity Score 28 (DAS-28), an established index of disease activity in rheumatoid arthritis between 0-10, where 10 equals maximum activity.	Change from baseline DAS-28 at 6 months
Secondary	Adherance to immunosuppressive therapy	Is the patient still prescribed the same immunosuppressant compared to baseline?	Analysis made at 6 months follow up
Secondary	Change in intestinal concentration Prevotella	Alterations in intestinal concentrations of Prevotella bacteria according to polymerase chain reaction (PCR)-based analysis	Change from baseline concentration at 6 months
Secondary	Change in intestinal concentration Lactobacillus	Alterations in intestinal concentrations of Lactobacillus bacteria according to PCR-based analysis	Change from baseline concentration at 6 months
Secondary	Change in intestinal concentration Clostridia	Alterations in intestinal concentrations of Clostridia bacteria according to PCR-based analysis	Change from baseline concentration at 6 months