Clinical trial NCT03944096: Efficacy and Safety of Fecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: fecal microbiota transplantation
methotrexate
rheumatoid arthritis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2019-05-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: The American College of Rheumatology 20 (ACR20) response at 16 weeks
timeFrame: week 16
Secondary outcomes:
measure: The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks
timeFrame: week 16
measure: The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
timeFrame: week 24
measure: The Disease Activity Score-28 (DAS28) response at 16 weeks
timeFrame: week 16
measure: The Disease Activity Score-28 (DAS28) response at 24 weeks
timeFrame: week 24
measure: The European League Against Rheumatism (EULAR) response at 16 weeks
timeFrame: week 16
measure: Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks
timeFrame: week 16
measure: Incidence of adverse events and sever adverse events (SAE) during the study
timeFrame: week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xuan Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: