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

NCT ID: NCT03944096

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2020-07-31

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:

1. To evaluate the efficacy of FMT with MTX for the treatment of signs and symptoms of RA in patients refractory to MTX.

2. 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:

1. FMT from healthy donor plus methotrexate

2. 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 :

1. Primary endpoint:

ACR20 response rates at 16 weeks.

2. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

FMT+MTX

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

Group Type: EXPERIMENTAL

FMT+MTX

Intervention Type: PROCEDURE

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

autologous FMT+MTX

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

Group Type: PLACEBO_COMPARATOR

FMT+MTX

Intervention Type: PROCEDURE

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

Interventions

FMT+MTX

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

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xuan Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xuan Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital

Locations

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yue Li, MD

Role: CONTACT

yuelee76@gmail.com

+8618601309256

Facility Contacts

Yue Li, MD

Role: primary

yuelee76@gmail.com

+8618601309256

Other Identifiers

FARM

Identifier Type: -

Identifier Source: org_study_id