Faecal Microbiota Transplantation to Ameliorate Nintedanib-induced Diarrhea in Patients With Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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This is a multicentric, randomised, double-blind, placebo-controlled study that will consist of two consecutive phases: First phase: faecal samples will be collected in patients diagnosed with Idiopathic pulmonary fibrosis treated with nintedanib. Second phase: double-blind, randomised, clinical trial of autologous faecal microbiota transplantation (FMT) vs placebo in Idiopathic pulmonary fibrosis patients who will experience nintedanib-induced diarrhea within 8 weeks of baseline visit. Follow-up visits will be scheduled at 1, 4 and 12 weeks after randomization. The main aim of the study is to assess the efficacy of FMT in ameliorating diarrhea experienced by patients with idiopathic pulmonary fibrosis treated with nintedanib.

Official Title
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Faecal Microbiota Transplantation to Ameliorate Nintedanib-induced Diarrhea in Patients With Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Procedure: Autologous FMT
* Procedure: Placebo FMT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1 (faecal samples collection) Patients aged ≥18 years when signing the informed consent; Diagnosis of IPF within 4 weeks based on 2018 ATS/ERS/JRS/ALAT Guidelines (2) as confirmed by the investigator based on chest HRCT scan and if available surgical lung biopsy; Patients already on antifibrotic therapy with nintedanib according to clinical practice. Phase 2 (FMT procedure) - Patients who develop diarrhea of grade 2 or 3 according to the Common Terminology Criteria (CTC) for Adverse Events (AE) version 5.0 (12) within 8 weeks of baseline visit. Exclusion Criteria: Women of childbearing potential or pregnant; History of colorectal surgery or cutaneous stoma; Food allergies; Recent (<6 weeks) therapy with drugs that could possibly alter gut microbiota (e.g. antibiotics, probiotics, proton pump inhibitors, immunosuppressants and/or metformin); Any documented active or suspected malignancy, except appropriately treated basal cell carcinoma of the skin, under surveillance prostate cancer or in situ carcinoma of uterine cervix; Decompensated heart failure or heart disease with ejection fraction lower than 30%, severe respiratory failure, psychiatric disorders, pregnancy or inability to provide informed consent. Fecal sample unable for FMT according to the opinion of the Investigators (e.g. positive for pathogens); (phase 2 only) Diarrhea from known causes (e.g. infectious gastroenteritis, Clostridium difficile infection, coeliac disease, inflammatory bowel disease, irritable bowel syndrome, chronic pancreatitis and/or biliary salt diarrhea).

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Faecal microbiota transplantation<br> | Procedure: Autologous FMT<br>* Autologous faecal microbiota transplantation by colonoscopy.<br>|
| Placebo Comparator: Placebo arm<br> | Procedure: Placebo FMT<br>* Placebo FMT will consist of 250 mL water. Placebo infusions will be delivered by colonoscopy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Resolution of diarrhea | Resolution of diarrhea at 4 weeks from FMT procedures. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Resolution of diarrhea | Resolution of diarrhea at 1 and 12 weeks from FMT procedures | 1 and 12 weeks | 
| Nintedanib discontinuation | Rate of nintedanib discontinuation or dose reduction | 12 weeks | 
| Intestinal microbiota composition | Analysis of intestinal microbiota composition at baseline and at 1, 4 and 12 weeks after the end of FMT procedures | 1, 4 and 12 weeks | 
| Forced vital capacity (FVC) | Relative and absolute change in forced vital capacity (FVC) percent-predicted from baseline at week 12 | 12 weeks | 
| St. George's Respiratory Questionnaire (SGRQ) | Change in St. George's Respiratory Questionnaire (SGRQ) score from baseline at week 12 | 12 weeks | 
| Exacerbation | Time to first acute exacerbation. | 12 weeks |