insulin-dependent diabetes juvenile diabetes Type 1 diabetes mellitus
Conditions
Interventions
Patients will be treated with infusion of allogenic or autologous feces by
duodenal tube after bowel lavage.
Type 1 diabetes mellitus patients will be randomized to the following 2
treatment arms:
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: -Patients with >5 years type 1 diabetes -Aged 18-65 years -BMI 18-30 kg/m2 -Male/females -No concomitant medication except insulin
Exclusion criteria
Exclusion criteria: -Inability to provide written informed consent -Evidence for absent residual beta cel function (undetectable C-peptide) -Antibiotics use in the last 3 months and proton-pump inhibitor use -Evidence for compromised immunity -Second auto-immune disease (i.e. coeliac disease, hyper- or hypothyroidism, inflammatory bowel disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| residual beta cell function Residual beta cell function will be measured by stimulated C-peptide response upon mixed-meal tolerance (MMTT) area under the curve (AUC0-120min) at 0, 2, 6, 9 and 12 months, using a 2 hour (-10, 0, 15, 30, 45, 60, 90, 120 min) mixed meal (MMT) test at 6 ml per kg body weight (max 360 ml per MMT of Sustacal Boost Nutritional Drink, Nestle HS, Switzerland: 33% carbohydrates, 57% fat and 15% protein). An AUC0-120 of plasma C-peptide upon the Boost mixed meal tolerance test (MMTT)) is then calculated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in immunologic tone II Immunologic parameters: In fresh whole blood samples, detailed multicolor flow cytometry is performed to characterize circulating immune cell fractions and specifically measure T-cell exhaustion. This includes monitoring of general leukocyte composition (monocyte/T/B/NK), granulocytes (Neu/Eo/Baso), particularly focusing at changes in the CD4, CD8 T cell and Treg compartments. Naturally occurring (nTreg) and induced regulatory T cells (tTreg) are analysed by surface and intracellular staining (CD25, CD127, CD122, FOXP3, IL-10, Ki67, CTLA-4, GITR, LAG-3, CD49b, ICOS and CD39). Detailed analyses of T-cell subsets allow quantification of naïve and memory subsets (using CD45RA, CCR7 and CD95), subsets of antigen-experienced T cells such as Th1, Th2, Th17, Tfh or Trm (using CXCR5, CCR4, CCR6, CXCR3 and CD103) and T cell exhaustion (using CD57, PD-1, Tim3 and CD69). This allows definition of more than 100 different cell subsets, approaching the analyzing resolution of the more expensive and less sensitive mass-spectrometry (CyTOF). Such analyses provide not only important information regarding the therapy induced changes but also allow comparisons of the results with trials testing other therapeutic approaches. We will collect pax-gene tubes to extract mRNA from whole blood. These measurements will be performed at the LUMC lab of Prof Roep, who is an expert in blood T cell tests in autoimmune diseases (15). Buffy coats will be stored for HLA and/or epigenetic analyses. We will use RNA seq on whole blood stored in a PAX-gene tube to measure expression patterns and we will use a machine learning algorithm to pinpoint which immune pathways are differentially expressed by FMT. Effect on intestinal gut microbiota composition upon multiple allogenic fecal infusions To assess therapy specificity morning stool samples will be collected -6, 0, 6 and 12 months in the study to determine microbiota composition. Samples will be | — |
Countries
Netherlands
Outcome results
None listed