Faecal Microbiota Transplantation Against Chronic Diarrhea in Patients With Systemic Sclerosis (FaeMiCue)

Faecal Microbiota Transplantation Against Chronic Diarrhea in Patients With Systemic Sclerosis - a Randomized, Double-blinded, Safety and Pilot-efficacy Study

This clinical trial aims to assess the safety and effectiveness of faecal Microbiota Transplantation (FMT) in improving chronic diarrhea symptoms among patients with systemic sclerosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Diarrhea; Systemic Sclerosis
• Intervention / Treatment: Procedure: Faecal Microbiota Transplantation (FMT); Procedure: Placebo

Detailed Description

The present study aims to assess the feasibility, pilot efficacy, and safety of FMT for patients with Systemic Sclerosis.

Participants will undergo two interventions in this present study.

In the first intervention, participants are randomized 1:1 for either active FMT or Placebo. This first intervention consists of two doses of FMT with a 3-7 day gap.

In the second intervention, all participants receive 1 dose of active FMT treatment.

This study design allows researchers to evaluate the safety of FMT in this patient group, and compare the effects of FMT in the FMT-treated group vs the placebo group, to see if FMT promotes remission of Chronic diarrhea. Furthermore, researchers will be able to gain insights into whether 2 initial doses are superior to one.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nanna S Rolighed, PhD-student; Phone Number: 52199715; Email: Nanna.rolighed@clin.au.dk
• Study Contact Backup: Name: Klaus Krogh, MD, DMSc; Phone Number: 23385937; Email: klaukrog@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants > 18 years
• Fulfilling and previously diagnosed with SSc according to the 2013 American College of Rheumatology/European League against rheumatisms SSs classification criteria[23] by rheumatologist or dermatologist.
• Chronic diarrea is defined as loose or watery stools, three or more times a day, a minimum of 50% of the days within the last four weeks.

Exclusion Criteria:

• Inability to understand Danish spoken or written and/or Trial procedures.
• Known or anticipated pregnancy (excluded by male sex, postmenopausal women, or otherwise negative U-HCG)
• Previous treatment with FMT
• Treatment with antibiotics within the past 6 weeks
• Changes in morphine treatment within the past 4 weeks
• Ongoing infection with Clostridioides difficile (negative PCR test)
• Known serious gastrointestinal disease or GI infection (diagnosed with e.g. inflammatory bowel disease and/or gastrointestinal cancer)
• Dysregulated thyroid disease (TSH) blood sample from previous consultations maximum 6 months old from
• Known intestinal stricture
• Planned MR scan within the study period
• Pacemaker/ICD
• Previous abdominal surgery (minor surgical procedures ex. appendectomy is allowed)
• Changes in medicine that affect the GI tract within the past four weeks.

• Known Severe end-organ disease

  • Lung disease with forced vital capacity(FVC)<50% and/or diffusing lung capacity for carbon monoxide (DLCO) <40%
  • Severe heart failure with ejection fraction <30%
  • End-stage kidney disease with glomeration rate<30ml/min

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
Experimental: Active treatment; Active capsule FMT-treatment	Procedure: Faecal Microbiota Transplantation (FMT); Treatment is given as capsules.
Placebo Comparator: Placebo; Placebo capsules are given.	Procedure: Placebo; Treatment is given as capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AE) severity grade 2 or more assessed by CTCAE v5.0. during the first week after intervention (FMT or placebo).	Patient-reported measures from the schedule of side effects and telephone call 1 week after each intervention.	The first week after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported treatment outcome on symptoms	Based on self-reported data from the bowel habit diary.	The first week after treatment.
Patient-reported measures from the schedule of side effects and telephone call 1 week after each intervention.	Mild adverse events (grade 1) following FMT or placebo assessed by (Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0) CTCAE v5.0. The CTCAE grades adverse events (AEs) based on severity: Grade 1: Mild, asymptomatic, or mild symptoms; no intervention needed. Grade 2: Moderate; requires minimal intervention; affects age-appropriate activities. Grade 3: Severe or medically significant, not immediately life-threatening; may require hospitalization. Grade 4: Life-threatening; urgent intervention needed. Grade 5: AE-related death. Note: Some AEs may not have all five grades available.	One week after each treatment
Patient-reported outcomes from questionnaires.	Change in Gastrointestinal syndrome rating scale - irritable bowel version questionnaire (GSRS-IBS)	At Baseline and 4 weeks after Intervention 1 & 2
Patient-reported outcomes from questionnaires.	Change in Wexner incontinence score.	At Baseline and 4 weeks after Intervention 1 & 2
Patient-reported outcomes from questionnaires.	Change in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0)	At Baseline and 4 weeks after Intervention 1 & 2
Patient-reported overall symptom burden	The patients self-reported the severity of symptoms and their impact on daily life each week on a scale from 1-5. 1 being little to no burden, 5 being most severe.	Each week for a total of 26 weeks.
Objective measures from the wireless motility capsule.	Transit time through the small intestine.	At baseline
Objective measures from the wireless motility capsule.	Colonic transit times	At baseline
Objective measures from the wireless motility capsule.	Total gastrointestinal transittimes	At baseline
Objective measures from the wireless motility capsule.	Ph drop from the small intestine to the colon	At baseline
Objective measures from the low-dose CT scan.	Volume of the a) small intestine and b) the colon. Volume of gas in a) the small intestine and b) the colon. Changes in the gas volume in the small intestine and colon.	At baseline and 4 weeks after first intervention
Breath Test	Changes in the rise of hydrogen and methane measured in breath test	At baseline and 4 weeks after first intervention
Faecal microbiota composition	Changes in faecal microbiome composition. Alfa and beta diversity determined by sequencing of the intestinal microbiome.	At baseline and between each treatment, up to 4 weeks after last intervention
Faecal-calprotectin	Percentual change in faecal-calprotectin from before intervention to 4 weeks after each intervention.	At Baseline and 4 weeks after Intervention 1 & 2
Blood plasma proteomics	Changes in blood immunological parameters (including proteins) from baseline and between each treatment, at 4 weeks after intervention.	At baseline and between each treatment, up to four weeks after last intervention.
Blood plasma Fibrosis markers	Changes in blood immunological parameters (including markers of fibrosis) from baseline and between each treatment, at 4 weeks after intervention.	At baseline and between each treatment, up to four weeks after last intervention.
Blood parameters	Changes in blood immunological parameters (including circulating cytokines) from baseline and between each treatment, at 4 weeks after intervention.	At baseline and between each treatment, up to four weeks after last intervention.
Health-related Quality of life	Changes in Health-related Quality of life assessed with (EQ-5D-5L). Each of the five dimensions comprising the EQ-5D descriptive system is divided into five levels of perceived problems: LEVEL 1: indicating no problem LEVEL 2: indicating slight problems LEVEL 3: indicating moderate problems LEVEL 4: indicating severe problems LEVEL 5: indicating unable to/Extreme problems An EQ-VAS from 0-100 is added, 100 being the best possible health.	At baseline and 4 weeks after Intervention 1 & 2
Patient perception of FMT treatment satisfaction	Patient perception of FMT treatment satisfaction was assessed by 7-point Likert scale for patients. 1: no benefits from treatment to 7 being very satisfied with treatment.	At 4 weeks after interventions 1 & 2

Collaborators and Investigators

• Sponsor: University of Aarhus

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Diarrhea; Systemic Sclerosis; Chronic Diarrhea; Faecal Microbiota Transplantation (FMT)
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Signs and Symptoms, Digestive; Connective Tissue Diseases; Sclerosis; Diarrhea; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: 1-10-72-131-23

Drug and device information, study documents

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