Prebiotics in Patients With Type 1 Diabetes
- Conditions
- Type 1 Diabetes
- Interventions
- Dietary Supplement: PlaceboDietary Supplement: Prebiotic
- Registration Number
- NCT04963777
- Lead Sponsor
- University of Calgary
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 144
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Maltodextrin Prebiotic Prebiotic Oligofructose-enriched inulin
- Primary Outcome Measures
Name Time Method Change in frequency of hypoglycemia 6 months Blood glucose \<3.9 mmol/L from continuous glucose monitor data
- Secondary Outcome Measures
Name Time Method 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 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 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 control post-intervention 9 months Glycated hemoglobin (A1C)
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 serum proinsulin 6 months Serum collected during a mixed meal tolerance test
Change in gut microbiota function 6 months Fecal microbiota shotgun sequencing
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.
Trial Locations
- Locations (3)
University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
University of Calgary
🇨🇦Calgary, Alberta, Canada