Fadigas: Faecal Microbiota Transplantation for Patients With Diabetes Mellitus Type 1 and Severe Gastrointestinal Neuropathy
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
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). [One week after the first intervention]
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. [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]
Stool consistency measured by the Bristol scale from 1(severe constipation) to 7 (severe diarrhea)
- Patient-reported outcomes obtained from the bowel habit diary. [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]
Median number of bowel openings per 24 hours.
- Patient-reported outcomes obtained from the bowel habit diary. [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]
Number of nightly bowel openings (from bedtime until morning).
- Patient-reported outcomes obtained from the bowel habit diary. [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]
Number of episodes with involuntary defaecation.
- Patient-reported outcomes obtained from the bowel habit diary. [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]
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. [One week after each intervention]
Mild adverse events (grade 1) following FMT or placebo assessed by CTCAE v5.0.
- Patient-reported outcomes from questionnaires. [at baseline and 4 weeks after each intervention period and at long term follow-up at week 26]
Change in Gastrointestinal syndrome rating scale - irritable bowel version questionnaire (GSRS-IBS)
- Patient-reported outcomes from questionnaires. [at baseline and 4 weeks after each intervention period and at long term follow-up at week 26]
Change in patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM)
- Patient-reported outcomes from questionnaires. [at baseline and 4 weeks after each intervention period and at long term follow-up at week 26]
Change in irritable bowel syndrome impact scale (IBS-IS)
- Objective measures from the wireless motility capsule. [at baseline and 4 weeks after each intervention period]
Transit time through the small intestine.
- Objective measures from the wireless motility capsule. [at baseline and 4 weeks after each intervention period]
Colonic transit time.
- Objective measures from the wireless motility capsule. [at baseline and 4 weeks after each intervention period]
pH drop from the small intestine to the colon.
- Objective measures from the low-dose CT scan. [at baseline and 4 weeks after the first intervention]
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. [at baseline and 4 weeks after the first intervention]
Rise in hydrogen PPM measured in breath test for small intestinal bacterial overgrowth.
- Microbiota analysis on faecal samples. [at baseline and 4 weeks after each intervention period]
Alpha-diversity of faecal microbiota, 16S. Dysbiosis index.
- Microbiota analysis on faecal samples. [at baseline and 4 weeks after each intervention period]
Dysbiosis index.
- Blood samples. [at baseline and 4 weeks after each intervention period]
Glycemic control measured by HbA1C levels.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University Hospital | Aarhus | Denmark | 8200 |
Sponsors and Collaborators
- University of Aarhus
Investigators
- Principal Investigator: Klaus Krogh, MD, DMSc, PhD, Professor, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Fadigas