Prebiotics in Newly Diagnosed Type 1 Diabetes

Study Overview
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Brief Summary
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Evidence suggests that prebiotic fibre can correct dysbiosis, reduce intestinal permeability and improve glycemic control. The investigators hypothesize that microbial changes induced by prebiotics contribute to gut and endocrine adaptations that reduce glucose fluctuations, including less hyper- and hypoglycemia in type 1 diabetes (T1D). The primary objective is to compare the change in frequency of hypoglycemia from baseline to 6 months in n=144 newly diagnosed (<12 months) individuals with T1D treated with a 6-month course of prebiotic or placebo as an adjunct to insulin. Secondary objectives will be aimed at understanding the mechanisms by which the prebiotics could affect glycemic control.

Detailed Description
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The investigators hypothesize that, as an adjunct to insulin, prebiotic supplementation will reduce the frequency of hypoglycemia and improve glycemic variability that is accompanied by enhanced serum C-peptide levels, a reduction in intestinal permeability and systemic inflammation, and altered gut microbiota. Primary Objective To compare the change in frequency of hypoglycemia from baseline to 6 months in newly diagnosed (<12 months) individuals with T1D treated with a 6-month course of prebiotic or placebo as an adjunct to insulin. Secondary Objectives To determine the change in glycemic variability and glycemic control using Continuous Glucose Monitor (CGM) metrics including: percentage change in Time In-, Below-, and Above-Range (i.e. TIR, TBR, and TAR) and A1C from baseline to 6 months in those treated with prebiotic or placebo. To compare the change in stimulated C-peptide and pro-insulin from baseline to 6 months. To determine the change in IP from baseline to 6 months. To determine the change in serum inflammatory markers (IL-6, IFN-gamma, TNF, C-reactive protein, and IL-10). To examine quality of life (QOL) and fear of hypoglycemia ratings, and adverse reactions (severe hypoglycemia, diabetic ketoacidosis, side effects). To examine prebiotic-induced changes in gut microbiota composition and function (shotgun sequencing) and their metabolic by-products (fecal and serum metabolomics).

Official Title
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Effect of Prebiotic Fibre on Glycemic Control, Gut Microbiota, and Intestinal Permeability in Newly Diagnosed (<12 Months) Type 1 Diabetes

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Dietary Supplement: Prebiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 1 diabetes (based on Diabetes Canada 2018 Clinical Practice Guideline diagnostic criteria) in the previous 12 months. Age 8 years and above (as per our pilot trial and able to complete the required tests). Exclusion Criteria: Regular use of medications or supplements that could affect gut microbiota (examples: antibiotics, probiotic or prebiotic supplements, laxatives) within 3 months prior to enrollment. Previous intestinal surgery. Another chronic medical condition that could affect gut microbiota or intestinal permeability (examples: Crohn's disease, Celiac disease, colitis, irritable bowel syndrome) Presence of active infection, pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-centre placebo controlled double-blind randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prebiotic<br>Oligofructose-enriched inulin | Dietary Supplement: Prebiotic<br>* Chicory root derived inulin-type fructan (13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ages ≥14 years)<br>|
| Placebo Comparator: Placebo<br>Maltodextrin | Dietary Supplement: Placebo<br>* Maltodextrin (isocaloric; 13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ≥14 years)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in frequency of hypoglycemia | Blood glucose <3.9 mmol/L from continuous glucose monitor data | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glycemic control | Glycated hemoglobin (A1C) | 6 months | 
| Change in stimulated C-peptide | Serum collected during a mixed meal tolerance test | 6 months | 
| Change in Intestinal permeability | Urinary lactulose/mannitol test | 6 months | 
| Change in Inflammatory marker IL-6 | Serum IL-6 | 6 months | 
| Change in quality of life | Diabetes-specific quality of life survey | 6 months | 
| Change in dietary intake | 24 hour dietary recall (energy intake, fat intake, carbohydrate intake, protein intake, fiber intake) | 6 months | 
| Change in gut microbiota composition | Fecal microbiota taxonomy | 6 months | 
| Change in gut microbiota function | Fecal microbiota shotgun sequencing | 6 months | 
| Change in serum metabolite concentration | Serum LC-Qtof-Mass Spec metabolomics | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut microbiota, Glycemic control, Prebiotic, Oligofructose-enriched inulin, Hypoglycemia