Safety and Efficacy of Capsule FMT in Treatment-naïve Patients With Newly Diagnosed Chronic Inflammatory Diseases

Study Overview
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Brief Summary
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PURPOSE: The main purpose is to explore clinical efficacy and safety associated with capsule FMT (cFMT) performed in newly diagnosed, untreated patients with rheumatic and gastrointestinal chronic inflammatory diseases (CIDs). DESIGN AND METHODS: In this 1:1 double-blind, placebo-controlled, randomised, 12-month exploratory trial, 200 patients with at least one of 6 different diagnoses of CIDs fulfilling the study criteria will be enrolled at time of diagnosis. The patient groups are: rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), pulmonary sarcoidosis (PSar), Crohn's disease (CD), and ulcerative colitis (UC). The primary endpoint is change from baseline to eight weeks in the physical component summary (PCS) of the short form health survey (SF-36). Key secondary clinical endpoints will be evaluated at 8 weeks. Other secondary clinical endpoints will be evaluated at 52 weeks and reported in secondary papers. The baseline visit will be performed as quickly as possible after the patient's informed consent has been obtained to ensure no unnecessary treatment delay. Stratified by CID diagnosis, patients will be randomised (1:1) to either placebo or single-donor cFMT processed from stool provided to the hospital from anonymous-to-the-patient healthy donors. The experimental intervention FMT/placebo will be repeated once weekly the first month (i.e., each patient will receive a total of four treatments). In addition, all participants will concomitantly be offered the national guideline first-line anti-inflammatory treatment following the baseline visit. At baseline, 8 weeks, 26 weeks, and 52 weeks a thorough clinical examination will be conducted and all relevant clinical scores for each disease entity will be registered. Patient-reported-outcomes including SF-36 and disease specific questionnaires will be collected at week 1, 2, 3, 4, 8 (primary endpoint evaluation), 26 and 52. Adverse events will be monitored through out the trial.

Official Title
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Safety and Clinical Efficacy Associated With Faecal Microbiota Transplantation Performed in Treatment-naïve Patients With Newly Diagnosed Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Pulmonary Sarcoidosis, Crohn's Disease, and Ulcerative Colitis: a 52-week, Double-blind, Randomised, Placebo-controlled, Exploratory Trial

Conditions
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Ulcerative Colitis, Rheumatoid Arthritis, Ankylosing Spondylitis, Psoriatic Arthritis, Pulmonary Sarcoidosis, Crohn Disease

Intervention / Treatment
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* Biological: Faecal microbiota transplantation
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Newly diagnosis of treatment-naïve RA, AS, PsA, PSar, CD, or UC. Treatment-naïve which is defined as no current or previous (within 3 months) disease-modifying anti-rheumatic drugs (DMARDs) or systemic anti-inflammatory treatment including glucocorticoids. Presence of CID treatment indication (no contra-indications) and patient accept to start first-line standard treatment in accordance with the national guideline for the specific diagnosis following the baseline visit. Age 18 to 75 years. Exclusion criteria: Indication for biological therapy as primary therapy. Celiac disease or food allergy. Current cancer. Hepatitis B and C, HIV, HTLV1/2, and active TB or other serious chronic infections. Pregnant or breastfeeding women. Not wishing to participate or not suited for FMT intervention or project evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cFMT<br> | Biological: Faecal microbiota transplantation<br>* The capsule FMT transplant consists of faeces obtained from a thoroughly screened, unpaid, anonymous stool donor. Each FMT product is made from 50g faeces diluted in sterile saline (0.9% NaCl) and glycerol, blended, centrifuged and filtered to remove particulate material before transfer to double-layered capsules. The FMT capsules will be stored at - 80 ⁰C until use. On the day of the FMT, the FMT capsules will be thawed to room temperature before treatment.<br>* Other names: capsule FMT;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo capsules consist of NaCl (0.9%) and glycerol added brown food colouring.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Component Summary score (PCS) | Change from baseline in the Physical Component Summary score (PCS) of the 36-Item Short Form Health Survey (SF-36) | 8 weeks (+/- 1 week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | Proportion of patients experiencing treatment failure at 8 weeks | 8 weeks (+/- 1 week) | 
| Mental Component Summary score (MCS) | Change from baseline in the Mental Component Summary score (MCS) of the 36-Item Short Form Health Survey (SF-36) | 8 weeks (+/- 1 week) | 
| Physician's Global Assessment | Change from baseline in the Physician's Global Assessment (0-100 mm VAS) | 8 weeks (+/- 1 week) | 
| Patient's Global Assessment | Change from baseline in the Patient's Global Assessment (0-100 mm VAS) | 8 weeks (+/- 1 week) | 
| Fatigue | Change from baseline in Fatigue visual analogue scales (0-100 mm VAS) | 8 weeks (+/- 1 week) | 
| C-reactive protein | Change from baseline in C-reactive protein | 8 weeks (+/- 1 week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Faecal microbiota transplantation, Fecal microbiota transplantation