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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Crohn Disease; Ulcerative Colitis; Psoriatic Arthritis; Ankylosing Spondylitis; Pulmonary Sarcoidosis
• Intervention / Treatment: Biological: Faecal microbiota transplantation; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Torkell Ellingsen, MD PhD; Phone Number: 0045 6611 3333; Email: torkell.ellingsen@rsyd.dk
• Study Contact Backup: Name: Maja S Kragsnaes, MD PhD; Email: maja.skov.kragsnaes@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital
    • Contact: Maja S Kragsnaes, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo capsules consist of NaCl (0.9%) and glycerol added brown food colouring.
Experimental: cFMT	Biological: Faecal microbiota transplantation; 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.; Other Names: capsule FMT

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other secondary endpoints, specific for each disease	Disease specific outcomes, not mentioned above	8 weeks (+/- 1 week)
Tertiary (secondary exploratory) endpoints	All of the above efficacy outcomes and safety outcomes assessed after 52 weeks	52 weeks (+/- 2 weeks)

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark; Region of Southern Denmark
• Investigators: Principal Investigator: Torkell Ellingsen, MD PhD, Odense University Hospital; Principal Investigator: Maja S Kragsnaes, MD PhD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Fecal microbiota transplantation; Faecal microbiota transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Infections; Respiratory Tract Diseases; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Autoimmune Diseases; Lung Diseases; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Skin Diseases, Papulosquamous; Hypersensitivity; Spinal Diseases; Bone Diseases; Inflammatory Bowel Diseases; Spondylarthropathies; Lung Diseases, Interstitial; Hypersensitivity, Delayed; Psoriasis; Bone Diseases, Infectious; Ankylosis; Axial Spondyloarthritis; Ulcer; Arthritis; Arthritis, Rheumatoid; Crohn Disease; Arthritis, Psoriatic; Colitis; Colitis, Ulcerative; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Sarcoidosis, Pulmonary; Sarcoidosis
• Other Study ID Numbers: 20/3106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available upon reasonable request. This will require review and approval by the trial scientific board and the data responsible parties. Terms of collaboration will be reached together with a signed collaboration agreement and data processor agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No