Prebiotics in Patients With Type 1 Diabetes

Effect of Prebiotic Fibre on Glycemic Control, Gut Microbiota, and Intestinal Permeability in 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 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 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.

• 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
    • Edmonton, Alberta, Canada, T6G 1C9
      • Recruiting
      • University of Alberta
      • Contact: Elizabeth Rosolowsky, MD, MPH; Phone Number: 780-248-5483; Email: Elizabeth.Rosolowsky@albertahealthservices.ca
      • Principal Investigator: Elizabeth Rosolowsky, MD, MPH
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 5E5
      • Recruiting
      • University of Saskatchewan
      • Contact: Munier Nour, MD, MSc; Phone Number: 306-655-2048; Email: munier.nour@usask.ca
      • Principal Investigator: Munier Nour, MD, MSc

Participation Criteria

Eligibility Criteria

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

Description

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.

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 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
Change in glycemic variability	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.	6 months
Change in serum proinsulin	Serum collected during a mixed meal tolerance test	6 months
Change in lipopolysaccharide	Serum lipopolysaccharide concentration	6 months
Change in Inflammatory marker IFN-γ	Serum IFN-γ	6 months
Change in Inflammatory marker TNF	Serum TNF	6 months
Change in Inflammatory marker CRP	Serum CRP	6 months
Change in Inflammatory marker IL-10	Serum IL-10	6 months
Change in fear of hypoglycemia	Fear of hypoglycemia ratings survey	6 months
Change in fecal metabolite concentrations	Serum LC-Qtof-Mass Spec metabolomics	6 months
Change in frequency of hypoglycemia post-intervention	Blood glucose <3.9 mmol/L from continuous glucose monitor data	9 months
Change in glycemic variability post-intervention	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.	9 months
Change in glycemic control post-intervention	Glycated hemoglobin (A1C)	9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in dietary intake	24 hour dietary recall (energy intake, kcal)	6 months
Change in dietary intake	24 hour dietary recall (fat intake, grams)	6 months
Change in dietary intake	24 hour dietary recall (carbohydrate intake, grams)	6 months
Change in dietary intake	24 hour dietary recall (protein intake, grams)	6 months
Change in dietary intake	24 hour dietary recall (fiber intake, grams)	6 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Huang C, Rosolowsky E, Nour MA, Butalia S, Ho J, Mayengbam S, Wang W, Pyke S, Virtanen H, Reimer RA. Prebiotic supplementation in patients with type 1 diabetes: study protocol for a randomised controlled trial in Canada. BMJ Open. 2025 May 31;15(5):e102486. doi: 10.1136/bmjopen-2025-102486.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2027

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): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Hypoglycemia; Prebiotic; Gut microbiota; Glycemic control; Oligofructose-enriched inulin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Hypoglycemia; Diabetes Mellitus, Type 1; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Carbohydrates; Carbohydrates; Polysaccharides; Dietary Fiber; Polysaccharides, Bacterial; Prebiotics
• Other Study ID Numbers: REB21-0852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified participant data will be available from the corresponding author upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No