Prebiotics in Newly Diagnosed Type 1 Diabetes

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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Dietary supplement: Prebiotic; Dietary supplement: Placebo

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

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).

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raylene A Reimer, PhD, RD; Phone Number: 403-220-8218; Email: reimer@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • Recruiting
      • University Of Calgary
      • Contact: Raylene A Reimer, PhD, RD; Phone Number: 403-220-8218; Email: reimer@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)
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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Raylene A Reimer, PhD, RD, University Of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 15, 2021

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Hypoglycemia; Prebiotic; Gut microbiota; Glycemic control; Oligofructose-enriched inulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: REB21-0852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No