Prebiotics in Newly Diagnosed Type 1 Diabetes

Sponsor

University of Calgary (Other)

Overall Status

Recruiting

CT.gov ID

NCT04963777

Collaborator

(none)

144

Enrollment

Location

Arms

53.1

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Dietary Supplement: Prebiotic Dietary Supplement: Placebo	N/A

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 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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multi-centre placebo controlled double-blind randomized clinical trialMulti-centre placebo controlled double-blind randomized clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

The prebiotic and placebo are both white powders with similar sweet taste and dissolve in water.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 29, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Prebiotic

Oligofructose-enriched inulin

Dietary Supplement: Prebiotic

Chicory root derived inulin-type fructan (13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ages ≥14 years)

Placebo Comparator: Placebo

Maltodextrin

Dietary Supplement: Placebo

Maltodextrin (isocaloric; 13.2 kcal/day for ages 8-13 years; 26.4 kcal/day for ≥14 years)

Outcome Measures

Primary Outcome Measures

Change in frequency of hypoglycemia [6 months]
Blood glucose <3.9 mmol/L from continuous glucose monitor data

Secondary Outcome Measures

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 Inflammatory marker IL-6 [6 months]
Serum IL-6
Change in quality of life [6 months]
Diabetes-specific quality of life survey
Change in dietary intake [6 months]
24 hour dietary recall (energy intake, fat intake, carbohydrate intake, protein intake, fiber intake)
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.