Rheumatoid ArthritisPhase 2FARMNCT03944096
Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate
A Phase 2 study testing FMT+MTX in people with Rheumatoid Arthritis, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
In this 24-week, single center, randomized, double-blind study, the investigators will evaluate the efficacy and safety of fecal microbiota transplantation in patients with active rheumatoid arthritis refractory to methotrexate Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- FMT+MTX
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2019to 31 Jul 2020
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65 years with informed consent
- Fulfill the 2010 ACR/EULAR classification criteria for rheumatoid arthritis
- Positive RF or anti-CCP antibody on screening
- Have active RA shown by swollen joint count(SJC)≥4 and tender joint count(TJC)≥4 and ESR >28 mm/hr or C-reactive protein > 1.5 ULN
- Have received methotrexate for 3 months or longer and at a stable dose of 7.5 to 25 mg/week (extremes included) for at least four weeks prior to screening and willing to continue on this regimen for the duration of the study.
- Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA
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- If taking oral steroids, these should be at a dose ≤10 mg/day of prednisone or prednisone equivalent and stable for at least four weeks prior to screening;
- If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least two weeks prior to screening;
- Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses);
- Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least four weeks after the last dose of study drug. Sexually active men must agree to use a medically acceptable form of contraception during the study and continue its use for at least 3 months after the last dose of study drug; and
- Willing to suspend the use of other adjuvant treatment for the duration of the study including acupuncture, massage, etc.
Who cannot join
- Pregnant, lactating or further fertility requirements
- History of any inflammatory rheumatological disorders other than RA;
- Previously received any biologic agents.
- Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background methotrexate;
- Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
- Active or chronic infection, including HIV, HCV, HBV, tuberculosis.
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- Malignancy or history of malignancy.
- Severe, progressive, or uncontrolled cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease
- unable to undergo colonoscopy.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100032
Yue Li, MD, +8618601309256, yuelee76@gmail.com
Xuan Zhang, MD
About this study
Official title: Efficacy and Safety of Faecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate: a 24-week, Double-Blind, Randomised Trial
In this 24-week, single center, randomized, double-blind study, the investigators will evaluate the efficacy and safety of fecal microbiota transplantation in patients with active rheumatoid arthritis refractory to methotrexate
Read the detailed description
Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by painful synovium inflammation, bony erosions, immune activation. Gut microbiota plays an important role in pathophysiology of RA. FMT(fecal microbiota transplantation) is the engraftment of microbiota from a healthy donor into a recipient to achieve restoration of the normal gut microbial community structure.This study evaluates the efficacy and safety of FMT with methotrexate in patients with active RA refractory to methotrexate
Objectives:
- To evaluate the efficacy of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX.
- To evaluate the safety of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX DESIGN
This is a Phase 2, randomized, 24-week, double-blind, parallel group study, and 30 patients with active RA refractory to MTX will be randomized in a 1:1 ratio to one of the following 2 parallel treatment arms:
- FMT from healthy donor plus methotrexate
- autologous FMT(from the participant himself/herself) plus methotrexate
Escape:
On week 16, all participants with inadequate response, defined as a <20% improvement of swollen and tender joint counts from baseline can switch type and dose of DMARDs.
Endpoints :
- Primary endpoint: ACR20 response rates at 16 weeks.
- Secondary endpoint： 1）ACR50 and ACR70 response at 16, 24 weeks，ACR20 response at 24 weeks. 2）DAS 28 (CRP) and DAS 28 (ESR) at 16 and 24 weeks. 3) EULAR response rates at 16 and 24 weeks. 4) Health assessment questionnaire (HAQ) at 16 and 24 weeks. 5) Patient assessment of arthritis pain at 16 and 24 weeks. 6) Patient and physician global assessment of arthritis at 16 and 24 weeks
- Conditions
- Rheumatoid Arthritis
- Being tested
- FMT+MTX
- Keywords
- fecal microbiota transplantation, methotrexate, rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMT+MTXProcedure or surgery
FMT is performed at the beginning of the study and is repeated after 4 weeks plus MTX in the same dose.
| Study group | Role | What they receive |
|---|---|---|
| FMT+MTX | Experimental | FMT One FMT is performed at baseline by gastroscopic guidance. The same FMT is repeated 4 weeks later. The transplant consists of 50 g mixed feces obtained from 3-5 non-related healthy donors. The donor feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the recipient.
Drug: Methotrexate (MTX) Weekly methotrexate Receives: Procedure: FMT+MTX |
| autologous FMT+MTX | Placebo comparator | autologous FMT (the feces used in FMT is from participant themselves) One identical FMT is performed at baseline using gastroscopic guidance and is repeated 4 weeks later. The corresponding participant's feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the participant himself or herself.
Drug: Methotrexate (MTX) Weekly methotrexate Receives: Procedure: FMT+MTX |
What is being measured
The primary outcome is the main question the study is designed to answer.
The American College of Rheumatology 20 (ACR20) response at 16 weeks
The difference of ACR20 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)
Measured: week 16
Secondary outcomes (7)
The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks
The difference of ACR50/70 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)
Measured: week 16
The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
The difference of ACR20, ACR50 and ACR70 between Arm 1 (FMT+MTX) and Arm 2(autologous FMT+MTX) at week 24
Measured: week 24
The Disease Activity Score-28 (DAS28) response at 16 weeks
The change in DAS28 score from baseline to week 16 between Arm 1 (FMT+MTX) and Arm 2(autologous FMT+MTX).
DAS28 ＝ 0.56*SQRT(TJC28) + 0.28*SQRT(SJC28) + 0.36*ln(CRP + 1) + 0.014*GH + 0.96 TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). CRP: The C-Reactive Protein level (in mg/l). GH: The patient global health assessment (from 0=best to 100=worst). The 28 joint: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees.
Measured: week 16
The Disease Activity Score-28 (DAS28) response at 24 weeks
The change in DAS28 score from baseline to week 24 between Arm 1 (FMT+MTX) and Arm 2(autologous FMT+MTX).
DAS28 ＝ 0.56*SQRT(TJC28) + 0.28*SQRT(SJC28) + 0.36*ln(CRP + 1) + 0.014*GH + 0.96 TJC28: The number of tender joints (0-28). SJC28: The number of swollen joints (0-28). CRP: The C-Reactive Protein level (in mg/l). GH: The patient global health assessment (from 0=best to 100=worst). The 28 joint: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees.
Measured: week 24
The European League Against Rheumatism (EULAR) response at 16 weeks
The difference of proportions of patients meeting EULAR response between Arm 1(FMT+MTX) and Arm 2 (autologous FMT+MTX) at week 16
Measured: week 16
Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks
The change in HAQ-DI score from baseline to week 16 between Arm 1(FMT+MTX) and Arm 2 (autologous FMT+MTX).
HAQ-DI is an index measuring the quality of life related to health, which includes 20 questions in terms of three categories:
from 0 to 1: mild difficulties to moderate disability, from 1 to 2: disability moderate to severe, from 2 to 3: severe to very severe disability. The mean score is recorded as the result.
Measured: week 16
Incidence of adverse events and sever adverse events (SAE) during the study
Safety profile
Measured: week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2019
- Study start30 Apr 2019
- Primary completion31 Mar 2020 (estimated)
- Study completion31 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xuan Zhang, Peking Union Medical College Hospital
- Investigators
- Xuan Zhang, MD, Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03944096
- Sponsor's protocol ID
- FARM
- Acronym
- FARM
- Status last verified
- May 2019
- First submitted
- 8 May 2019
- Last updated
- 23 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Faecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate: a 24-week, Double-Blind, Randomised Trial
- ClinicalTrials.gov ID
- NCT03944096
- Acronym / sponsor ID
- FARM / FARM
- Conditions
- Rheumatoid Arthritis
- Keywords
- fecal microbiota transplantation, methotrexate, rheumatoid arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 30 Apr 2019 (actual)
- Primary completion
- 31 Mar 2020 (estimated)
- Study completion
- 31 Jul 2020 (estimated)
- First posted
- 9 May 2019 (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.
In this 24-week, single center, randomized, double-blind study, the investigators will evaluate the efficacy and safety of fecal microbiota transplantation in patients with active rheumatoid arthritis refractory to methotrexate
Detailed description
Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by painful synovium inflammation, bony erosions, immune activation. Gut microbiota plays an important role in pathophysiology of RA. FMT(fecal microbiota transplantation) is the engraftment of microbiota from a healthy donor into a recipient to achieve restoration of the normal gut microbial community structure.This study evaluates the efficacy and safety of FMT with methotrexate in patients with active RA refractory to methotrexate
Objectives:
- To evaluate the efficacy of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX.
- To evaluate the safety of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX DESIGN
This is a Phase 2, randomized, 24-week, double-blind, parallel group study, and 30 patients with active RA refractory to MTX will be randomized in a 1:1 ratio to one of the following 2 parallel treatment arms:
- FMT from healthy donor plus methotrexate
- autologous FMT(from the participant himself/herself) plus methotrexate
Escape:
On week 16, all participants with inadequate response, defined as a <20% improvement of swollen and tender joint counts from baseline can switch type and dose of DMARDs.
Endpoints :
- Primary endpoint: ACR20 response rates at 16 weeks.
- Secondary endpoint： 1）ACR50 and ACR70 response at 16, 24 weeks，ACR20 response at 24 weeks. 2）DAS 28 (CRP) and DAS 28 (ESR) at 16 and 24 weeks. 3) EULAR response rates at 16 and 24 weeks. 4) Health assessment questionnaire (HAQ) at 16 and 24 weeks. 5) Patient assessment of arthritis pain at 16 and 24 weeks. 6) Patient and physician global assessment of arthritis at 16 and 24 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FMT+MTX | Experimental | Procedure: FMT+MTXFMT One FMT is performed at baseline by gastroscopic guidance. The same FMT is repeated 4 weeks later. The transplant consists of 50 g mixed feces obtained from 3-5 non-related healthy donors. The donor feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the recipient. Drug: Methotrexate (MTX) Weekly methotrexate |
| autologous FMT+MTX | Placebo comparator | Procedure: FMT+MTXautologous FMT (the feces used in FMT is from participant themselves) One identical FMT is performed at baseline using gastroscopic guidance and is repeated 4 weeks later. The corresponding participant's feces is suspended into NaCl (0.9%) and glycerol (10%), and will be stored at minus 80 degrees celsius until use. The total volume of the suspension is 150 mL and its temperature will be 37 degrees celsius when infused into ileus of the participant himself or herself. Drug: Methotrexate (MTX) Weekly methotrexate |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18-65 years with informed consent
- Fulfill the 2010 ACR/EULAR classification criteria for rheumatoid arthritis
- Positive RF or anti-CCP antibody on screening
- Have active RA shown by swollen joint count(SJC)≥4 and tender joint count(TJC)≥4 and ESR >28 mm/hr or C-reactive protein > 1.5 ULN
- Have received methotrexate for 3 months or longer and at a stable dose of 7.5 to 25 mg/week (extremes included) for at least four weeks prior to screening and willing to continue on this regimen for the duration of the study.
Key exclusion criteria (9 listed)
- Pregnant, lactating or further fertility requirements
- History of any inflammatory rheumatological disorders other than RA;
- Previously received any biologic agents.
- Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background methotrexate;
- Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
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 |
|---|---|---|
| FMT+MTXFMT is performed at the beginning of the study and is repeated after 4 weeks plus MTX in the same dose. | Procedure or surgery | FMT+MTX, autologous FMT+MTX |
Primary outcome
The American College of Rheumatology 20 (ACR20) response at 16 weeks
Time frame: week 16
The difference of ACR20 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)
7 secondary outcomes
The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks
Time frame: week 16
The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
Time frame: week 24
The Disease Activity Score-28 (DAS28) response at 16 weeks
Time frame: week 16
The Disease Activity Score-28 (DAS28) response at 24 weeks
Time frame: week 24
The European League Against Rheumatism (EULAR) response at 16 weeks
Time frame: week 16
Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks
Time frame: week 16
Incidence of adverse events and sever adverse events (SAE) during the study
Time frame: week 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2019.
- Individual participant dataSharing planned: Undecided
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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.
Xuan Zhang, MD principal investigator
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FMT+MTX in people with Rheumatoid Arthritis, run by Peking Union Medical College Hospital at 1 site in China.
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 11 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 23 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yue Li, MD (+8618601309256, yuelee76@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The American College of Rheumatology 20 (ACR20) response at 16 weeks (time frame: week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 May 2019.