Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy (Fadigas)
Primary Purpose
Faecal Microbiota Transplantation (FMT), Diabetes Mellitus, Type 1, Gastrointestinal Neuropathy
Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Faecal microbiota transplantation (FMT) capsules
Placebo capsules
Sponsored by
About this trial
This is an interventional treatment trial for Faecal Microbiota Transplantation (FMT)
Eligibility Criteria
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
Sites / Locations
- Aarhus University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Placebo Comparator
Arm Label
Faecal microbiota transplantation (FMT)
Placebo
Arm Description
Donor faeces is obtained from thoroughly screened healthy blood donors and processed in compliance with the European Tissue and Cells Directive.
Placebo capsules will be identical in terms of visual appearance, weight, and vials and number
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Patient-reported outcomes obtained from the bowel habit diary.
Stool consistency measured by the Bristol scale from 1(severe constipation) to 7 (severe diarrhea)
Patient-reported outcomes obtained from the bowel habit diary.
Median number of bowel openings per 24 hours.
Patient-reported outcomes obtained from the bowel habit diary.
Number of nightly bowel openings (from bedtime until morning).
Patient-reported outcomes obtained from the bowel habit diary.
Number of episodes with involuntary defaecation.
Patient-reported outcomes obtained from the bowel habit diary.
Glycemic control measured by patient reported use of insulin (IE).
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.
Patient-reported outcomes from questionnaires.
Change in Gastrointestinal syndrome rating scale - irritable bowel version questionnaire (GSRS-IBS)
Patient-reported outcomes from questionnaires.
Change in patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM)
Patient-reported outcomes from questionnaires.
Change in irritable bowel syndrome impact scale (IBS-IS)
Objective measures from the wireless motility capsule.
Transit time through the small intestine.
Objective measures from the wireless motility capsule.
Colonic transit time.
Objective measures from the wireless motility capsule.
pH drop from the small intestine to the colon.
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.
Objective measures from the breath test.
Rise in hydrogen PPM measured in breath test for small intestinal bacterial overgrowth.
Microbiota analysis on faecal samples.
Alpha-diversity of faecal microbiota, 16S. Dysbiosis index.
Microbiota analysis on faecal samples.
Dysbiosis index.
Blood samples.
Glycemic control measured by HbA1C levels.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04749030
Brief Title
Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy
Acronym
Fadigas
Official Title
Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy: a Randomised, Double-blinded Safety and Pilot-efficacy Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
February 28, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Faecal Microbiota Transplantation (FMT), Diabetes Mellitus, Type 1, Gastrointestinal Neuropathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
The study is a 8-week, randomised, double-blinded, placebo-controlled pilot trial of oral FMT versus placebo in patients with DM1 and severe GI neuropathy. The intervention period consists of a first 4 weeks where patients receive either FMT or placebo and a second 4 weeks where all patients receive FMT. The patients will undergo the investigations before and after each 4-week period.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Faecal microbiota transplantation (FMT)
Arm Type
Other
Arm Description
Donor faeces is obtained from thoroughly screened healthy blood donors and processed in compliance with the European Tissue and Cells Directive.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo capsules will be identical in terms of visual appearance, weight, and vials and number
Intervention Type
Other
Intervention Name(s)
Faecal microbiota transplantation (FMT) capsules
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo capsules
Intervention Description
The placebo capsules are produced from a suspension of 50% glycerol, 40% sterile saline and 10% food coloring in enterocapusles
Primary Outcome Measure Information:
Title
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).
Description
Patient-reported measures from the schedule of side effects and telephone call 1 week after each intervention.
Time Frame
One week after the first intervention
Secondary Outcome Measure Information:
Title
Patient-reported outcomes obtained from the bowel habit diary.
Description
Stool consistency measured by the Bristol scale from 1(severe constipation) to 7 (severe diarrhea)
Time Frame
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
Title
Patient-reported outcomes obtained from the bowel habit diary.
Description
Median number of bowel openings per 24 hours.
Time Frame
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
Title
Patient-reported outcomes obtained from the bowel habit diary.
Description
Number of nightly bowel openings (from bedtime until morning).
Time Frame
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
Title
Patient-reported outcomes obtained from the bowel habit diary.
Description
Number of episodes with involuntary defaecation.
Time Frame
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
Title
Patient-reported outcomes obtained from the bowel habit diary.
Description
Glycemic control measured by patient reported use of insulin (IE).
Time Frame
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
Title
Patient-reported measures from the schedule of side effects and telephone call 1 week after each intervention.
Description
Mild adverse events (grade 1) following FMT or placebo assessed by CTCAE v5.0.
Time Frame
One week after each intervention
Title
Patient-reported outcomes from questionnaires.
Description
Change in Gastrointestinal syndrome rating scale - irritable bowel version questionnaire (GSRS-IBS)
Time Frame
at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Title
Patient-reported outcomes from questionnaires.
Description
Change in patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM)
Time Frame
at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Title
Patient-reported outcomes from questionnaires.
Description
Change in irritable bowel syndrome impact scale (IBS-IS)
Time Frame
at baseline and 4 weeks after each intervention period and at long term follow-up at week 26
Title
Objective measures from the wireless motility capsule.
Description
Transit time through the small intestine.
Time Frame
at baseline and 4 weeks after each intervention period
Title
Objective measures from the wireless motility capsule.
Description
Colonic transit time.
Time Frame
at baseline and 4 weeks after each intervention period
Title
Objective measures from the wireless motility capsule.
Description
pH drop from the small intestine to the colon.
Time Frame
at baseline and 4 weeks after each intervention period
Title
Objective measures from the low-dose CT scan.
Description
Volume of the a) small intestine and b) the colon. Volume of gas in a) the small intestine and b) the colon.
Time Frame
at baseline and 4 weeks after the first intervention
Title
Objective measures from the breath test.
Description
Rise in hydrogen PPM measured in breath test for small intestinal bacterial overgrowth.
Time Frame
at baseline and 4 weeks after the first intervention
Title
Microbiota analysis on faecal samples.
Description
Alpha-diversity of faecal microbiota, 16S. Dysbiosis index.
Time Frame
at baseline and 4 weeks after each intervention period
Title
Microbiota analysis on faecal samples.
Description
Dysbiosis index.
Time Frame
at baseline and 4 weeks after each intervention period
Title
Blood samples.
Description
Glycemic control measured by HbA1C levels.
Time Frame
at baseline and 4 weeks after each intervention period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katrine L Høyer, MD
Phone
+45 21956352
Email
kathoeye@rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Klaus Krogh, MD, DMSc, PhD, Professor
Organizational Affiliation
Department of Hepatology and Gastroenterology, Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katrine L Høyer, MD
Phone
+45 21956352
Email
kathoeye@rm.dk
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28863010
Citation
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.
Results Reference
background
Learn more about this trial
Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy
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