Diabetes Mellitus, Type 1, Faecal Microbiota Transplantation (FMT), Gastrointestinal Neuropathy
Conditions
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.
Interventions
OTHERFaecal 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).
OTHERPlacebo capsules
The placebo capsules are produced from a suspension of 50% glycerol, 40% sterile saline and 10% food coloring in enterocapusles
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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) |
| 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 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. |
| Blood samples. | at baseline and 4 weeks after each intervention period | Glycemic control measured by HbA1C levels. |
| 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. |
Countries
Denmark
Outcome results
None listed