Back to results

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate (FARM)

Primary Purpose

Rheumatoid Arthritis

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

FMT+MTX

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring fecal microbiota transplantation, methotrexate, rheumatoid arthritis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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.

Exclusion Criteria:

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.
Malignancy or history of malignancy.
Severe, progressive, or uncontrolled cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease
unable to undergo colonoscopy.

Sites / Locations

Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

FMT+MTX

autologous FMT+MTX

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)

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

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.

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.

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

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.

Incidence of adverse events and sever adverse events (SAE) during the study

Safety profile

Full Information

NCT ID

NCT03944096

First Posted

May 8, 2019

Last Updated

May 21, 2019

Sponsor

Peking Union Medical College Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03944096

Brief Title

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate

Acronym

FARM

Official Title

Efficacy and Safety of Faecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate: a 24-week, Double-Blind, Randomised Trial

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Unknown status

Study Start Date

April 30, 2019 (Actual)

Primary Completion Date

March 31, 2020 (Anticipated)

Study Completion Date

July 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

fecal microbiota transplantation, methotrexate, rheumatoid arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

FMT+MTX

Arm Type

Experimental

Arm Description

Arm Title

autologous FMT+MTX

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Procedure

Intervention Name(s)

FMT+MTX

Intervention Description

FMT is performed at the beginning of the study and is repeated after 4 weeks plus MTX in the same dose.

Primary Outcome Measure Information:

Title

The American College of Rheumatology 20 (ACR20) response at 16 weeks

Description

The difference of ACR20 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)

Time Frame

week 16

Secondary Outcome Measure Information:

Title

The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks

Description

The difference of ACR50/70 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)

Time Frame

week 16

Title

The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks

Description

The difference of ACR20, ACR50 and ACR70 between Arm 1 (FMT+MTX) and Arm 2(autologous FMT+MTX) at week 24

Time Frame

week 24

Title

The Disease Activity Score-28 (DAS28) response at 16 weeks

Description

Time Frame

week 16

Title

The Disease Activity Score-28 (DAS28) response at 24 weeks

Description

Time Frame

week 24

Title

The European League Against Rheumatism (EULAR) response at 16 weeks

Description

The difference of proportions of patients meeting EULAR response between Arm 1(FMT+MTX) and Arm 2 (autologous FMT+MTX) at week 16

Time Frame

week 16

Title

Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks

Description

Time Frame

week 16

Title

Incidence of adverse events and sever adverse events (SAE) during the study

Description

Safety profile

Time Frame

week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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. Exclusion Criteria: 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. Malignancy or history of malignancy. Severe, progressive, or uncontrolled cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease unable to undergo colonoscopy.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yue Li, MD

Phone

+8618601309256

yuelee76@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xuan Zhang, MD

Organizational Affiliation

Peking Union Medical College Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking Union Medical College Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yue Li, MD

Phone

+8618601309256

yuelee76@gmail.com

First Name & Middle Initial & Last Name & Degree

Xuan Zhang, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate

We'll reach out to this number within 24 hrs