Juveline diabetes type 1 diabetes mellitus
Conditions
Interventions
After the 3 month run-in phase of the study, patients will be treated on a
daily basis with capsules containing lyophilized autologous faecal matter for a
period of 3 months. During the run-in phase
Sponsors
Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Male or female recently diagnosed (0.5-3.5 years) with type 1 diabetes mellitus. 2. Age: 18-65 years 3. BMI: 18-30 kg/m2 4. Remaining (detectable) residual beta cell function: detectable urinary or plasma C- peptide at inclusion of the study.
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. History or symptoms of other autoimmune disease (e.g. hypo- or hyperthyroidism, rheumatoid arthritis). 2. (Expected) prolonged comprised immunity (e.g. due to recent cytotoxic chemotherapy or human immunodeficiency virus (HIV) infection with a CD4 count =3 stools/day for >4 weeks), chronic obstipation (3 months), Irritable Bowel Syndrome (IBS) (according to Rome IV criteria) or Inflammatory Bowel Disease (IBD). 4. Use of antibiotics, antacid drugs or proton pump inhibitors in the past 3 months or during the study period. 5. Use of pro-/prebiotics in the past three months or during the study period. 6. Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period. 7. Use of >21 units of alcohol per week on average in the past three months 8. Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Preservation of residual beta cell function (insulin secretion capacity) Residual beta cell function will be determined as stimulated C-peptide release during two hours (AUC0-120min) upon an MMT. The MMT will be performed during every visit at -3, 0, 3 and 6 months. C-peptide concentrations will be presented as pmol/ml. | — |
Secondary
| Measure | Time frame |
|---|---|
| Glycaemic control To investigate overt effects of the intervention on glycaemic control we will collect fasting blood for determination of glucose, HbA1c, lipid spectrum, liver and kidney function (eGFR). Albumin will be measured in urine (microalbuminuria). In addition, we will read-out participants continuous glucose monitoring device (Freestyle Libre) for their time in range and hyper- and hypo glycaemic episodes and we will record the exogenous insulin dose use. Above measurements will be performed during every visit at -3, 0, 3 and 6 months. Intestinal microbiota composition We will determine changes in faecal gut microbiota composition at -3, 0, 3 and 6 months as well as changes in small intestinal microbiota composition at 0 and 3 months. The faecal gut microbiota composition will be determined from faecal samples, collected by the participants at home. The small intestinal microbiota composition will be determined from duodenal biopsies obtained via gastroscopy. DNA will be extracted from duodenal biopsies and faecal samples, which will be shotgun sequenced on an Illumina platform. Intestinal microbiota metabolites We will determine changes in (microbial) metabolite composition from fasting plasma samples obtained during the MMT and from 24h urine samples collected at -3, 0, 3 and 6 months. Metabolites will be measured by liquid chromatography-mass spectrometry for metabolomics. Questionnaires and dietary intake At each study visit questionnaires will be completed determine changes in: - Diabetic complications, hypoglycaemic episodes, insulin dosages and medication changes - Hypo-awareness - Gastro-intestinal complaints - Dietary intake 3 days prior to visit Autoimmunity markers As we found that baseline immune status predicts response to FMT, detailed multicolour flow cytometry is performed at the first study visit to characterize circulating immune cell fractions and specifically measure T-cell exhaustion. This includes mon | — |
Countries
Netherlands
Outcome results
None listed