Rheumatoid ArthritisFARTNCT03775824
Faecal Analyses in Rheumatoid Arthritis Therapy
An observational study of Rheumatoid Arthritis, run by Region Skane.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- MTX start and TNF start
- Type of treatment
- Injection or infusion
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2016to 1 Jun 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Rheumatoid arthritis according to the 2010 classification criteria
- About to start methotrexate or TNF-inhibitor because of active disease
Who cannot join
- 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
About this study
Official title: Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
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.
Read the 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
- Being tested
- MTX start, TNF start
- Keywords
- microbiome, methotrexate, tnf-inhibitor, dysbiosis
- Medical subject headings
- Arthritis, Rheumatoid, Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTX startDrug
Also called MTX
Patient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis
TNF startDrug
Also called TNF
Patient prescribed TNF-inhibitor because of active rheumatoid arthritis
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MTX start | |
| 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 Receives: Drug: TNF start |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intestinal gut flora in rheumatoid arthritis
Intestinal gut flora based on DNA-based microbial analysis of fecal samples
Measured: Analysis made at study start/baseline
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/
Measured: Change from baseline Dysbiosis Index Score at 6 months
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.
Measured: Change from baseline DAS-28 at 6 months
Secondary outcomes (4)
Adherance to immunosuppressive therapy
Is the patient still prescribed the same immunosuppressant compared to baseline?
Measured: Analysis made at 6 months follow up
Change in intestinal concentration Prevotella
Alterations in intestinal concentrations of Prevotella bacteria according to polymerase chain reaction (PCR)-based analysis
Measured: Change from baseline concentration at 6 months
Change in intestinal concentration Lactobacillus
Alterations in intestinal concentrations of Lactobacillus bacteria according to PCR-based analysis
Measured: Change from baseline concentration at 6 months
Change in intestinal concentration Clostridia
Alterations in intestinal concentrations of Clostridia bacteria according to PCR-based analysis
Measured: Change from baseline concentration at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2018
- Study start1 Aug 2016
- Primary completion1 Nov 2018
- Study completion1 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristofer Andreasson, Region Skane
- Investigators
- Kristofer Andréasson, MD PhD, Principal investigator, Skane University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775824
- Sponsor's protocol ID
- FART1
- Acronym
- FART
- Status last verified
- Sep 2019
- First submitted
- 11 Dec 2018
- Last updated
- 16 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27894337Zhang 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.
PubMed 26214836Pianta 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.
PubMed 28650341
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Faecal Analyses in Rheumatoid Arthritis Therapy: An Prospective Observational Study of the Intestinal Microbiome in Patients With Rheumatoid Arthritis Receiving Immunosuppressive Therapy
- ClinicalTrials.gov ID
- NCT03775824
- Acronym / sponsor ID
- FART / FART1
- Conditions
- Rheumatoid Arthritis
- Keywords
- microbiome, methotrexate, tnf-inhibitor, dysbiosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 1 Nov 2018 (actual)
- Study completion
- 1 Jun 2019 (actual)
- First posted
- 14 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MTX start | – | Drug: MTX startPatients 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. |
| TNF start | – | Drug: TNF startPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- Rheumatoid arthritis according to the 2010 classification criteria
- About to start methotrexate or TNF-inhibitor because of active disease
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTX startAlso: MTXPatient prescribed MTX s.c. or p.o. because of active rheumatoid arthritis | Drug | MTX start |
| TNF startAlso: TNFPatient prescribed TNF-inhibitor because of active rheumatoid arthritis | Drug | TNF start |
Primary outcome
Intestinal gut flora in rheumatoid arthritis
Time frame: Analysis made at study start/baseline
Intestinal gut flora based on DNA-based microbial analysis of fecal samples
Change in gut flora
Time frame: Change from baseline Dysbiosis Index Score at 6 months
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 in disease activity/treatment response at follow up
Time frame: Change from baseline DAS-28 at 6 months
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.
4 secondary outcomes
Adherance to immunosuppressive therapy
Time frame: Analysis made at 6 months follow up
Change in intestinal concentration Prevotella
Time frame: Change from baseline concentration at 6 months
Change in intestinal concentration Lactobacillus
Time frame: Change from baseline concentration at 6 months
Change in intestinal concentration Clostridia
Time frame: Change from baseline concentration at 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2019.
- Background: PubMed 27894337Andreasson 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.
- Background: PubMed 26214836Zhang 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.
- Background: PubMed 28650341Pianta 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristofer Andréasson, MD PhD principal investigator
Skane University Hospital
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Region Skane.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intestinal gut flora in rheumatoid arthritis (time frame: Analysis made at study start/baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03775824, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2019.