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

Rheumatoid Arthritis Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03944096
• Other study ID #: FARM
• Status: Recruiting
• Phase: Phase 2
• Start date: April 30, 2019
• Est. completion date: July 31, 2020

Study information

• Verified date: May 2019
• Source: Peking Union Medical College Hospital
• Contact: Yue Li, MD
• Phone: +8618601309256
• Email: yuelee76[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	week 16
Secondary	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)	week 16
Secondary	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	week 24
Secondary	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.	week 16
Secondary	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.	week 24
Secondary	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	week 16
Secondary	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.	week 16
Secondary	Incidence of adverse events and sever adverse events (SAE) during the study	Safety profile	week 24