Faecal Microbiota Transplantation Against Chronic Diarrhea in Patients With Systemic Sclerosis

Not Applicable

Not yet recruiting

• Conditions: Systemic Sclerosis; Diarrhea
• Interventions: Procedure: Faecal Microbiota Transplantation (FMT); Procedure: Placebo

• Registration Number: NCT06333795
• Lead Sponsor: University of Aarhus

Brief Summary

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.

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 Timeline

• Status Verified: 2024-03
• Study First Submitted: 2024-03-05
• Study First Submitted QC: 2024-03-20
• Last Update Submitted: 2024-03-20
• Study First Posted: 2024-03-27
• Last Update Posted: 2024-03-27
• Study Start: 2024-04-01
• Primary Completion: 2025-01-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active treatment	Faecal Microbiota Transplantation (FMT)	Active capsule FMT-treatment
Placebo	Placebo	Placebo capsules are given.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Blood plasma Fibrosis markers	At baseline and between each treatment, up to four weeks after last intervention.	Changes in blood immunological parameters (including markers of fibrosis) from baseline and between each treatment, at 4 weeks after intervention.
Blood parameters	At baseline and between each treatment, up to four weeks after last intervention.	Changes in blood immunological parameters (including circulating cytokines) from baseline and between each treatment, at 4 weeks after intervention.
Patient-reported outcomes from questionnaires.	At Baseline and 4 weeks after Intervention 1 & 2	Change in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0)
Objective measures from the wireless motility capsule.	At baseline	Ph drop from the small intestine to the colon
Patient-reported treatment outcome on symptoms	The first week after treatment.	Based on self-reported data from the bowel habit diary.
Faecal microbiota composition	At baseline and between each treatment, up to 4 weeks after last intervention	Changes in faecal microbiome composition. Alfa and beta diversity determined by sequencing of the intestinal microbiome.
Blood plasma proteomics	At baseline and between each treatment, up to four weeks after last intervention.	Changes in blood immunological parameters (including proteins) from baseline and between each treatment, at 4 weeks after intervention.
Patient-reported measures from the schedule of side effects and telephone call 1 week after each intervention.	One week after each treatment	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.
Patient-reported overall symptom burden	Each week for a total of 26 weeks.	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.
Objective measures from the low-dose CT scan.	At baseline and 4 weeks after first intervention	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.
Breath Test	At baseline and 4 weeks after first intervention	Changes in the rise of hydrogen and methane measured in breath test
Faecal-calprotectin	At Baseline and 4 weeks after Intervention 1 & 2	Percentual change in faecal-calprotectin from before intervention to 4 weeks after each intervention.
Health-related Quality of life	At baseline and 4 weeks after Intervention 1 & 2	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.
Patient perception of FMT treatment satisfaction	At 4 weeks after interventions 1 & 2	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.

Trial Locations

Locations (1)

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark