Clinical trial NCT04963777: Prebiotics in Patients With Type 1 Diabetes
Official title: Effect of Prebiotic Fibre on Glycemic Control, Gut Microbiota, and Intestinal Permeability in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Gut microbiota
Glycemic control
Prebiotic
Oligofructose-enriched inulin
Hypoglycemia
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2021-07-15
Enrollment: 144
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-centre placebo controlled double-blind randomized clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in frequency of hypoglycemia
timeFrame: 6 months
Secondary outcomes:
measure: Change in glycemic variability
timeFrame: 6 months
measure: Change in glycemic control
timeFrame: 6 months
measure: Change in stimulated C-peptide
timeFrame: 6 months
measure: Change in serum proinsulin
timeFrame: 6 months
measure: Change in Intestinal permeability
timeFrame: 6 months
measure: Change in lipopolysaccharide
timeFrame: 6 months
measure: Change in Inflammatory marker IL-6
timeFrame: 6 months
measure: Change in Inflammatory marker IFN-γ
timeFrame: 6 months
measure: Change in Inflammatory marker TNF
timeFrame: 6 months
measure: Change in Inflammatory marker CRP
timeFrame: 6 months
measure: Change in Inflammatory marker IL-10
timeFrame: 6 months
measure: Change in quality of life
timeFrame: 6 months
measure: Change in fear of hypoglycemia
timeFrame: 6 months
measure: Change in gut microbiota composition
timeFrame: 6 months
measure: Change in gut microbiota function
timeFrame: 6 months
measure: Change in serum metabolite concentration
timeFrame: 6 months
measure: Change in fecal metabolite concentrations
timeFrame: 6 months
measure: Change in frequency of hypoglycemia post-intervention
timeFrame: 9 months
measure: Change in glycemic variability post-intervention
timeFrame: 9 months
measure: Change in glycemic control post-intervention
timeFrame: 9 months
Other outcomes:
measure: Change in dietary intake
timeFrame: 6 months
measure: Change in dietary intake
timeFrame: 6 months
measure: Change in dietary intake
timeFrame: 6 months
measure: Change in dietary intake
timeFrame: 6 months
measure: Change in dietary intake
timeFrame: 6 months
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Calgary
name: Raylene A Reimer, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References: