Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Обзор

This clinical trial will investigate the effects of capsules containing stool from healthy donors, called fecal microbial transplant (FMT), in rheumatoid arthritis patients.

Подробное описание

This is a randomized double-blind placebo-controlled proof-of-concept trial. A total of 30 RA patients will be asked to join the study. They will be randomized to receive capsular FMT + standard of care or placebo + standard of care. There will be four study visits in total: Baseline, FMT administration, 6- and 12-week follow-up visits. Follow-up visits will consist of assessment by a rheumatologist, completion of surveys, and collection of biologic samples.

Samples for the study are stool, urine and blood. Blood and fecal samples will be collected at baseline, 6 weeks and 12 weeks. Urine samples will be collected at baseline and 6 weeks.

Вмешательства

• Препарат Fecal Microbial transplant
  Fecal microbial transplant will be investigated for its effect on gut bacterial composition in patients with rheumatoid arthritis.
• Другое Placebo capsules
  The placebo capsules will not contain FMT but will have the same appearance.

Первичные конечные точки

• Change in Intestinal Permeability [Срок оценки: Baseline and 6 weeks]
• Change in Intestinal Permeability [Срок оценки: Baseline and 6 weeks]
• Change in RA-associated autoantibodies [Срок оценки: Baseline, 6 weeks and 12 weeks]
• Adverse Events [Срок оценки: Baseline]
• Adverse Events [Срок оценки: FMT treatment visit]
• Adverse Events [Срок оценки: 6 weeks post-treatment]
• Adverse Events [Срок оценки: 12 weeks post-treatment]

Вторичные конечные точки (2)

• Change in Fecal Microbial Composition [Срок оценки: Baseline, 6 weeks and 12 weeks]
• Change in C-Reactive Protein [Срок оценки: Baseline, 6 weeks and 12 weeks.]

Критерии участия

Критерии включения

• 18-years old or older
• RA diagnosis by ACR/EULAR criteria \[26\]
• Positive for the RA-associated antibodies, anti-citrullinated protein/peptide antibodies (ACPA) and/or rheumatoid factor (RF)
• Stable RA therapy > 6 months
• Patient in remission or low disease activity by DAS28
• Consents to study

Fecal Donor Inclusion Criteria:

• A healthy donor who has a normal body mass index (BMI of 18.5-30) and who satisfies the following criteria will be selected from a pool of donors available in the Infectious Diseases clinic at St. Joseph's Hospital supervised by Dr. Silverman and screened for all transmissible agents. at the Microbiology and Immunology lab at St. Joseph's Hospital under Dr. Silverman for the study and screened for transmissible agents.

Критерии исключения

• Pregnant or breastfeeding
• Current or recent \[in the last 60 days\] exposure to high dose oral (>30 mg of prednisone daily or equivalent), IV corticosteroids, biologic therapies or JAKi.
• Patients who require inhaled steroids or local steroid injections are not excluded from the study
• Has a diagnosis of immunodeficiency (HIV, transplantation, or autoimmune disease other than RA requiring immunosuppressive therapies), or currently receiving systemic steroid therapy (>10 mg prednisone daily or equivalent)
• Received rituximab or other chemotherapeutic agent in the last 2 years.
• Expected to require any other form of systemic or localized anti-neoplastic therapy while on study
• Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years. NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.
• Ongoing use of antibiotics/anti-virals or previous use of antibiotics/anti-virals in the last 3 months prior to the FMT procedure
• Has an active infection requiring systemic therapy or requiring hospital admission in last 3 months.
• Presence of a chronic intestinal disease (e.g. Celiac disease, malabsorption, colonic tumor, IBD)
• Presence of absolute contra-indications to FMT administration
• Toxic megacolon
• Anaphylactic allergic reactions to food (e.g. shellfish, nuts, seafood, eggs)
• Has serious uncontrolled concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), severe obstructive or restrictive pulmonary diseases, cirrhosis or ALT>100, renal disease with GFR<50 and uncontrolled psychiatric illness.
• Patient has received a live vaccine within 4 weeks prior to the first dose of treatment
• Insulin-dependent diabetes
• Previous bariatric surgery
• Chronic neutropenia (<0.5) Currently participating in another clinical trial

Fecal Donor Exclusion Criteria:

• Any underlying metabolic disease including; hypertension, hyperlipidemia, diabetes, insulin insensitivity, atherosclerosis
• A history of any gastrointestinal or liver disorders or cancers. Including but not limited to; gastroesophageal reflux, peptic ulcer disease, celiac disease, inflammatory bowel disease (Crohn's disease or ulcerative colitis), microscopic colitis, motility disorders (including gastroparesis and irritable bowel syndrome) diverticular disease
• Previous surgery to the intestine, liver or gallbladder (except remote appendectomy)
• History of any malignancy
• Use within 3 months of any antibiotics
• Hospitalization within 3 months
• Recent travel to a developing country (within 3 months).
• New Sexual Partner (within 3 months)
• Street drug use, family history of diabetes, early onset coronary disease or gastrointestinal or liver disease, colon cancer, familial malignancy
• Psychiatric history (major affective disorder, psychotic illness, ongoing use of any psychiatric medications)
• Any positive laboratory results for a transmissible pathogen
• Alcohol intake with a cut off value of <10g/d in women and <20g/d in men
• Currently participating in another clinical trial that may alter fecal composition.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• St. Joseph's Health Care London — London

Публикации

• Bykerk VP, Akhavan P, Hazlewood GS, Schieir O, Dooley A, Haraoui B, Khraishi M, Leclercq SA, Legare J, Mosher DP, Pencharz J, Pope JE, Thomson J, Thorne C, Zummer M, Bombardier C; Canadian Rheumatology Association. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol PMID 21921096
• Barnabe C, Sun Y, Boire G, Hitchon CA, Haraoui B, Thorne JC, Tin D, van der Heijde D, Curtis JR, Jamal S, Pope JE, Keystone EC, Bartlett S, Bykerk VP; CATCH Investigators. Heterogeneous Disease Trajectories Explain Variable Radiographic, Function and Quality of Life Outcomes in the Canadian Early Arthritis Cohort (CATCH). PLoS One. 2015 Aug 24;10(8):e0135327. doi: 10.1371/journal.pone.0135327. eCo PMID 26301589
• Bombardier C, Hazlewood GS, Akhavan P, Schieir O, Dooley A, Haraoui B, Khraishi M, Leclercq SA, Legare J, Mosher DP, Pencharz J, Pope JE, Thomson J, Thorne C, Zummer M, Gardam MA, Askling J, Bykerk V; Canadian Rheumatology Association. Canadian Rheumatology Association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirhe PMID 22707613
• Munro S, Spooner L, Milbers K, Hudson M, Koehn C, Harrison M. Perspectives of patients, first-degree relatives and rheumatologists on preventive treatments for rheumatoid arthritis: a qualitative analysis. BMC Rheumatol. 2018 Jul 5;2:18. doi: 10.1186/s41927-018-0026-7. eCollection 2018. PMID 30886969
• Loyola-Sanchez A, Hazlewood G, Crowshoe L, Linkert T, Hull PM, Marshall D, Barnabe C. Qualitative Study of Treatment Preferences for Rheumatoid Arthritis and Pharmacotherapy Acceptance: Indigenous Patient Perspectives. Arthritis Care Res (Hoboken). 2020 Apr;72(4):544-552. doi: 10.1002/acr.23869. PMID 30821924
• Taylor PC, Ancuta C, Nagy O, de la Vega MC, Gordeev A, Jankova R, Kalyoncu U, Lagunes-Galindo I, Morovic-Vergles J, de Souza MPGUES, Rojkovich B, Sidiropoulos P, Kawakami A. Treatment Satisfaction, Patient Preferences, and the Impact of Suboptimal Disease Control in a Large International Rheumatoid Arthritis Cohort: SENSE Study. Patient Prefer Adherence. 2021 Feb 17;15:359-373. doi: 10.2147/PPA.S2 PMID 33633444
• Deane KD, Holers VM. Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift. Arthritis Rheumatol. 2021 Feb;73(2):181-193. doi: 10.1002/art.41417. Epub 2020 Dec 8. PMID 32602263
• Wilson AS, Koller KR, Ramaboli MC, Nesengani LT, Ocvirk S, Chen C, Flanagan CA, Sapp FR, Merritt ZT, Bhatti F, Thomas TK, O'Keefe SJD. Diet and the Human Gut Microbiome: An International Review. Dig Dis Sci. 2020 Mar;65(3):723-740. doi: 10.1007/s10620-020-06112-w. PMID 32060812

Идентификаторы

NCT: NCT05790356 · FeMiTRA01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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