Type 1 Diabetes
Conditions
Keywords
Gut microbiota, Glycemic control, Prebiotic, Oligofructose-enriched inulin, Hypoglycemia
Brief summary
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 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
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 individuals with T1D treated with a 6-month course of prebiotic or placebo as an adjunct to insulin. Secondary Objectives 1. 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. 2. To compare the change in stimulated C-peptide and pro-insulin from baseline to 6 months. 3. To determine the change in IP from baseline to 6 months. 4. To determine the change in serum inflammatory markers (IL-6, IFN-gamma, TNF, C-reactive protein, and IL-10). 5. To examine quality of life (QOL) and fear of hypoglycemia ratings, and adverse reactions (severe hypoglycemia, diabetic ketoacidosis, side effects). 6. To examine prebiotic-induced changes in gut microbiota composition and function (shotgun sequencing) and their metabolic by-products (fecal and serum metabolomics). 7. To compare the change in frequency of hypoglycemia from baseline to 9 months to determine persistence of effects post-intervention. 8. To determine the change in glycemic variability from baseline to 9 months to determine persistence of effects post-intervention.
Interventions
DIETARY_SUPPLEMENTPrebiotic
Chicory root derived inulin-type fructan (13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ages ≥14 years)
DIETARY_SUPPLEMENTPlacebo
Maltodextrin (isocaloric; 13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ≥14 years)
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The prebiotic and placebo are both white powders with similar sweet taste and dissolve in water.
Intervention model description
Multi-centre placebo controlled double-blind randomized clinical trial
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Lead Site: * Diagnosed with type 1 diabetes (based on Diabetes Canada 2018 Clinical Practice Guideline diagnostic criteria) in the previous 12 months. * Age 7 years and above (as per our pilot trial and able to complete the required tests). Subsites: * Diagnosed with type 1 diabetes (based on Diabetes Canada 2018 Clinical Practice Guideline diagnostic criteria) in the previous 12 months. * Age 7 to 17 years of age.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in frequency of hypoglycemia | 6 months | Blood glucose \<3.9 mmol/L from continuous glucose monitor data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in glycemic variability | 6 months | CGM-recorded composite of percentage of 'time-in-range" (glucose of 3.9-10 mmol/L), "time-below-range" as mild (glucose 3.0-3.9 mmol/L) or moderate (glucose \<3.0 mmol/L) hypoglycemia, and "time-above- range" as moderate (glucose 10.1-13.9 mmol/L) and severe (glucose \>13.9 mmol/L) hyperglycemia. |
| Change in glycemic control | 6 months | Glycated hemoglobin (A1C) |
| Change in stimulated C-peptide | 6 months | Serum collected during a mixed meal tolerance test |
| Change in serum proinsulin | 6 months | Serum collected during a mixed meal tolerance test |
| Change in Intestinal permeability | 6 months | Urinary lactulose/mannitol test |
| Change in lipopolysaccharide | 6 months | Serum lipopolysaccharide concentration |
| Change in Inflammatory marker IL-6 | 6 months | Serum IL-6 |
| Change in Inflammatory marker IFN-γ | 6 months | Serum IFN-γ |
| Change in Inflammatory marker TNF | 6 months | Serum TNF |
| Change in Inflammatory marker CRP | 6 months | Serum CRP |
| Change in Inflammatory marker IL-10 | 6 months | Serum IL-10 |
| Change in quality of life | 6 months | Diabetes-specific quality of life survey |
| Change in fear of hypoglycemia | 6 months | Fear of hypoglycemia ratings survey |
| Change in gut microbiota composition | 6 months | Fecal microbiota taxonomy |
| Change in gut microbiota function | 6 months | Fecal microbiota shotgun sequencing |
| Change in serum metabolite concentration | 6 months | Serum LC-Qtof-Mass Spec metabolomics |
| Change in fecal metabolite concentrations | 6 months | Serum LC-Qtof-Mass Spec metabolomics |
| Change in frequency of hypoglycemia post-intervention | 9 months | Blood glucose \<3.9 mmol/L from continuous glucose monitor data |
| Change in glycemic variability post-intervention | 9 months | CGM-recorded composite of percentage of 'time-in-range" (glucose of 3.9-10 mmol/L), "time-below-range" as mild (glucose 3.0-3.9 mmol/L) or moderate (glucose \<3.0 mmol/L) hypoglycemia, and "time-above- range" as moderate (glucose 10.1-13.9 mmol/L) and severe (glucose \>13.9 mmol/L) hyperglycemia. |
| Change in glycemic control post-intervention | 9 months | Glycated hemoglobin (A1C) |
Countries
Canada
Contacts
CONTACTRaylene A Reimer, PhD, RD
PRINCIPAL_INVESTIGATORRaylene A Reimer, PhD, RD
University of Calgary
Outcome results
None listed