Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy (Fadigas)

Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy: a Randomised, Double-blinded Safety and Pilot-efficacy Study

A randomised, double-blinded and placebo-controlled intervention study. The study aim to evaluate the feasibility, safety and pilot-efficacy of faecal microbiota transplantation as a treatment of severe gastrointestinal neuropathy in patients with diabetes mellitus type 1.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Faecal Microbiota Transplantation (FMT); Gastrointestinal Neuropathy
• Intervention / Treatment: Other: Faecal microbiota transplantation (FMT) capsules; Other: Placebo capsules

Detailed Description

Diabetes type 1 may cause damage to nerve cells in the gut causing neuropathy that leads to changes in gastric and intestinal motility. This change predisposes to an abnormal amounts and composition of bacteria in the gut, probably leading to uncontrollable diarrhea and severely impaired quality of life. Transferal of intestinal microbiota from a healthy donor to a patient is called faecal microbiota transplantation (FMT). FMT may potentially change the bacteria in the gut and reduce gastrointestinal symptoms. However, FMT may also have potential side effects, especially in persons with autonomic neuropathy and delayed transit through the gut.

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

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Adult (≥ 18 years old), male or female patients with DM1 for at least 5 years and average of or above 40 points in the questionnaire: Gastrointestinal syndrome rating scale - irritable bowel syndrome version (GSRS-IBS).

Exclusion Criteria:

• Inability to understand Danish or the trial procedures
• Known or anticipated pregnancy
• Known severe renal insufficiency
• Antibiotic use in the prior 4 weeks
• Treatment with morphine
• Ongoing infection with Clostridioides difficile or pathogenic intestinal bacteria or parasites
• Known gastrointestinal disease or GI infection
• Patients diagnosed with intestinal stricture
• Patients with other known disorder that can cause gastroparesis
• Patients with planned MR scan within 4 weeks
• Patients with pacemaker/ICD
• Previous abdominal surgery
• Changes in medicine that affects the GI tract in the prior 4 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Faecal microbiota transplantation (FMT); Donor faeces is obtained from thoroughly screened healthy blood donors and processed in compliance with the European Tissue and Cells Directive.	Other: Faecal microbiota transplantation (FMT) capsules; The faeces is minimally processed through a series of centrifugation steps and dispensed into double-coated, acid resistant enterocapsules. A single treatment includes approximately 22 capsules (~50 grams of original donor faeces).
Placebo Comparator: Placebo; Placebo capsules will be identical in terms of visual appearance, weight, and vials and number	Other: Placebo capsules; The placebo capsules are produced from a suspension of 50% glycerol, 40% sterile saline and 10% food coloring in enterocapusles

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported outcomes obtained from the bowel habit diary.	Stool consistency measured by the Bristol scale from 1(severe constipation) to 7 (severe diarrhea)	Each patient fills out the diary every day for one week at baseline, for one week starting at each day of the two interventions and for one week at the long term follow-up at week 26
Patient-reported outcomes obtained from the bowel habit diary.	Median number of bowel openings per 24 hours.	Each patient fills out the diary every day for one week at baseline, for one week starting at each day of the two interventions and for one week at the long term follow-up at week 26
Patient-reported outcomes obtained from the bowel habit diary.	Number of nightly bowel openings (from bedtime until morning).	Each patient fills out the diary every day for one week at baseline, for one week starting at each day of the two interventions and for one week at the long term follow-up at week 26
Patient-reported outcomes obtained from the bowel habit diary.	Number of episodes with involuntary defaecation.	Each patient fills out the diary every day for one week at baseline, for one week starting at each day of the two interventions and for one week at the long term follow-up at week 26
Patient-reported outcomes obtained from the bowel habit diary.	Glycemic control measured by patient reported use of insulin (IE).	Each patient fills out the diary every day for one week at baseline, for one week starting at each day of the two interventions and for one week at the long term follow-up at week 26
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 CTCAE v5.0.	One week after each intervention
Patient-reported outcomes from questionnaires.	Change in Gastrointestinal syndrome rating scale - irritable bowel version questionnaire (GSRS-IBS)	at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Patient-reported outcomes from questionnaires.	Change in patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM)	at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Patient-reported outcomes from questionnaires.	Change in irritable bowel syndrome impact scale (IBS-IS)	at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Objective measures from the wireless motility capsule.	Transit time through the small intestine.	at baseline and 4 weeks after each intervention period
Objective measures from the wireless motility capsule.	Colonic transit time.	at baseline and 4 weeks after each intervention period
Objective measures from the wireless motility capsule.	pH drop from the small intestine to the colon.	at baseline and 4 weeks after each intervention period
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.	at baseline and 4 weeks after the first intervention
Objective measures from the breath test.	Rise in hydrogen PPM measured in breath test for small intestinal bacterial overgrowth.	at baseline and 4 weeks after the first intervention
Microbiota analysis on faecal samples.	Alpha-diversity of faecal microbiota, 16S. Dysbiosis index.	at baseline and 4 weeks after each intervention period
Microbiota analysis on faecal samples.	Dysbiosis index.	at baseline and 4 weeks after each intervention period
Blood samples.	Glycemic control measured by HbA1C levels.	at baseline and 4 weeks after each intervention period

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Klaus Krogh, MD, DMSc, PhD, Professor, Department of Hepatology and Gastroenterology, Aarhus University Hospital

Publications and helpful links

General Publications

• Jorgensen SMD, Hansen MM, Erikstrup C, Dahlerup JF, Hvas CL. Faecal microbiota transplantation: establishment of a clinical application framework. Eur J Gastroenterol Hepatol. 2017 Nov;29(11):e36-e45. doi: 10.1097/MEG.0000000000000958.

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): October 1, 2023
• Study Completion (Actual): October 1, 2023

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: Fadigas

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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