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The goal is to establish the effect of oral probiotic Desulfovibrio piger (D. piger) supplementation on immunological and metabolic parameters in individuals with longstanding type 1 diabetes with residual beta cell function. The investigators will perform a double-blind, randomized, placebo-controlled trial in 2x10 participants to measure effects of D. piger on parameters of systemic and intestinal inflammation and residual beta cell function.
The investigators perform a double-blind, randomized, placebo-controlled trial with two arms (10 participants per arm, total of 20 participants) in adults with longstanding type 1 diabetes with residual beta cell function. The study duration is 6 weeks, with 4 weeks of intervention in which participants will be given D. piger or placebo once daily and 2 weeks of washout period. The main study enpoints include the changes (versus baseline) in parameters of systemic/intestinal inflammation and beta cell function between the placebo and D.piger-treatment arms at the end of treatment (4 weeks). In addition, any long-lasting effects will be determined by assessing the changes in the above described markers after a 2 week washout period (6 weeks).
Secondary endpoints include glucose variability (continuous glucose monitoring, CGM), fecal microbiome composition (including strain engraftment of D. piger, plasma metabolites), immune cell phenotype and frequency and validated questionnaires (gastro-intestinal complaints) at these three timepoints (0,4,6 weeks).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotic Desulfovibrio piger | Experimental | Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin) |
|
| Placebo | Placebo Comparator | placebo (10ml PBS containing 10% glycerol and 10% maltodextrin) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Probiotic dietary supplement | Dietary Supplement | Probiotic bacteria D. piger (10^9 colony forming units (CFU) in 10ml PBS containing 10% glycerol and 10% maltodextrin) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Parameters of systemic and intestinal inflammation | systemic inflammation determined by measuring plasma CRP, and proinflammatory cytokines (IFNgamma, IFN alpha, TNFalpha) intestinal inflammation assessed by LB, iFABP, zonulin in plasma | From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Residual beta cell function | Assessed by C peptide AUC during mixed meal tolerance test and/or post meal urine C-peptide/creatinine ratio levels. | From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Glucose variability | percentage time in euglycemic range, time above range, time below range and glucose variability measured by continuous glucose monitoring (CGM) | From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Immune cell phenotypes and frequency |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Max Nieuwdorp, Prof. Dr. | Contact | +31 20-5669111 | m.nieuwdorp@amsterdamumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Max Nieuwdorp, Prof. Dr. | Amsterdam UMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Diabeter Centrum Amsterdam | Recruiting | Amsterdam | 1066 EC | Netherlands |
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2x10 participants will be randomly allocated to probiotic D. piger or placebo once daily for 4 weeks.
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The unblinded researcher will provide the study intervention to the blinded investigator in a coded fashion. Both the investigator and the participant are blinded. In case of emergency, an unblinding protocol is activated.
| Placebo | Dietary Supplement | Placebo (10ml PBS containing 10% glycerol and 10% maltodextrin) |
|
Immunophenotyping by flow cytometry of PBMC (peripheral blood mononuclear cells) to determine frequency of T cell subsets with activation/exhaustion marker expression |
| From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Fecal microbiome composition and strain engraftment | using 16s rRNA sequencing, primer-specific quantitative PCR for D. piger detection in feces and plasma metabolites | From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Gastrointestinal Symptom Rating Scale (GSRS) | Questionnaire. The minimum and maximum score are 15 and 105 points respectively, and a higher score in the scale reflects more gastro-intestinal complaints. | From start treatment to the end of treatment at 4 weeks and washout at 6 weeks. |
| Amsterdam UMC | Recruiting | Amsterdam | 1105 AZ | Netherlands |
|
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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