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Trial record 38 of 91 for:    Recruiting Studies | fecal microbiota transplantation

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

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ClinicalTrials.gov Identifier: NCT03944096
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Xuan Zhang, Peking Union Medical College Hospital

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

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Procedure: FMT+MTX Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Faecal Microbiota Transplantation in Patients With Rheumatoid Arthritis Refractory to Methotrexate: a 24-week, Double-Blind, Randomised Trial
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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

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

Placebo Comparator: 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

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




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. The American College of Rheumatology 50/70 (ACR50/ACR70) response at 16 weeks [ Time Frame: week 16 ]
    The difference of ACR50/70 between Arm 1 (FMT+MTX) and Arm 2 (autologous FMT+MTX)

  2. The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks [ Time Frame: week 24 ]
    The difference of ACR20, ACR50 and ACR70 between Arm 1 (FMT+MTX) and Arm 2(autologous FMT+MTX) at week 24

  3. The Disease Activity Score-28 (DAS28) response at 16 weeks [ Time Frame: week 16 ]

    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.


  4. The Disease Activity Score-28 (DAS28) response at 24 weeks [ Time Frame: week 24 ]

    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.


  5. The European League Against Rheumatism (EULAR) response at 16 weeks [ Time Frame: week 16 ]
    The difference of proportions of patients meeting EULAR response between Arm 1(FMT+MTX) and Arm 2 (autologous FMT+MTX) at week 16

  6. Health Assessment Questionnaire without Didability Index (HAQ-DI) at 16 weeks [ Time Frame: week 16 ]

    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.


  7. Incidence of adverse events and sever adverse events (SAE) during the study [ Time Frame: week 24 ]
    Safety profile



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944096


Contacts
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Contact: Yue Li, MD +8618601309256 yuelee76@gmail.com

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100032
Contact: Yue Li, MD    +8618601309256    yuelee76@gmail.com   
Principal Investigator: Xuan Zhang, MD         
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
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Principal Investigator: Xuan Zhang, MD Peking Union Medical College Hospital

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Responsible Party: Xuan Zhang, Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03944096     History of Changes
Other Study ID Numbers: FARM
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xuan Zhang, Peking Union Medical College Hospital:
fecal microbiota transplantation
methotrexate
rheumatoid arthritis

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors