Prebiotic Fiber Supplement in T1DM Children

Effect of Prebiotic Fiber on Gut Microbiota, Intestinal Permeability and Glycemic Control in Children With Type 1 Diabetes: A Pilot Randomized, Double Blind, Placebo Controlled Study

The gut microbiome is increasingly recognized as a contributor to disease states. In type 1 diabetes, alterations in gut microbiota may be linked to changes in intestinal permeability, inflammation and insulin resistance. Prebiotic fiber is a dietary supplement that alters gut microbiota and could potentially improve insulin sensitivity in children with type 1 diabetes. This pilot study aims to determine the feasibility of a 12-week dietary intervention with prebiotic fiber in children with type 1 diabetes. The investigators hypothesize that consumption of prebiotic fiber will alter gut microbiota and intestinal permeability, leading to improved glycemic control. Prebiotic fiber is a potentially novel, inexpensive, low-risk treatment addition for type 1 diabetes that may improve glycemic control by changes in gut microbiota, gut permeability and inflammation.

Study Overview

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

Detailed Description

At baseline, each subject will complete a demographic questionnaire (age, gender, date of type 1 diabetes diagnosis, current medications, other medical conditions, number of episodes of severe hypoglycemia and diabetic ketoacidosis since diagnosis of type 1 diabetes) and an anthropometric data form (height, weight, body mass index). A baseline stool sample will be collected at home. One tablespoon of stool will be placed in a pre-labelled sterile conical tube, placed in a biohazard bag and stored in the home freezer (-20°C). Stool samples will be brought to the laboratory on ice within 3 days from collection and stored at -80°C until analysis. Subjects will have a baseline blood sample drawn for HbA1c, C-peptide, and inflammatory markers (IL-6, IFN-γ, TNF-α, and IL-10), GLP1 and GLP2. An intestinal permeability test will be performed as described below.

Subjects will be randomized to receive either placebo (maltodextrin 3.3 g orally/ day) or prebiotic fiber (1:1 oligofructose: inulin 8 g orally /day). Both are approved as food ingredients in Canada and not regulated as natural health products. Dr. Reimer has a 'no objection' letter from Health Canada and has previously used these in a clinical trial (14).

Both prebiotic fiber and placebo come in a powder form in a pre-measured packet. Subjects will be instructed to mix the packet with 250 mL water until dissolved and to take 15-20 minutes prior to their evening meal. For the first two weeks, subjects will be asked to only take half of the dose in order to minimize GI side effects and then they will take the full dose for the remaining 10 weeks. Subjects will be asked to record any diabetes related adverse reactions (ie. severe hypoglycemia and diabetic ketoacidosis). At the end of the 12 weeks (3months), subjects will be asked to submit a second stool sample and repeat baseline blood tests and intestinal permeability testing. Subjects will be asked to return any remaining packets of placebo or prebiotic in order to assess for compliance. A third stool sample, intestinal permeability testing and blood sample (HbA1c, C-peptide, inflammatory markers (IL-6, IFN-γ, TNF-α, and IL-10), GLP1 and GLP2) will be done at 6 months follow up. Telephone contact from a member of the research team (research assistant or PI) will occur monthly to encourage compliance and recording of adverse reactions.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Alberta Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 8 - 17 years old
2. Diagnosed with type 1 diabetes for at least one year
3. HbA1c <10% for 6 month prior to start of trial

Exclusion Criteria:

1. Subjects with another chronic medical condition that could affect gut microbiota (examples: Crohn's disease, cystic fibrosis, irritable bowel syndrome, etc.)
2. Subjects taking medications or supplements that could affect gut microbiota (examples: antibiotics, probiotics, prebiotics, laxatives, etc.)
3. Subjects with a positive celiac disease screen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; maltodextrin 3.3 g orally/ day for 12 weeks	Dietary supplement: Placebo; maltodextrin 3.3g orally/day
EXPERIMENTAL: Prebiotic; 1:1 oligofructose: inulin 8 g orally /day for 12 weeks	Dietary supplement: Prebiotic; 1:1 oligofructose: inulin 8 g orally /day; Other Names: OFS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic control (serum hemoglobin A1c)	measure serum level of hemoglobin A1c	3 month after start of trial

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota composition (mRNA in stool)	measure mRNA in stool	3 month after start of trial
Gut microbiota composition (mRNA in stool)	measure mRNA in stool	6 month after start of trial
Glycemic control (as measured by serum hemoglobin A1c)	measure serum level of hemoglobin A1c	6 month after start of trial

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
hypoglycemia (patient self report)	patient self report	for the entire 6 month after start of the trial
Change in gut permeability (quantification of specific sugars in urine)	measure by amount of mannitol and lactulose in urine	3-month after start of the trial
Change in gut permeability (quantification of specific sugars in urine)	measure by amount of mannitol and lactulose in urine	6-month after start of the trial

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Carol Huang, MD, PhD, University of Calgary

Publications and helpful links

General Publications

• Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, Huang C. Effect of Prebiotic on Microbiota, Intestinal Permeability, and Glycemic Control in Children With Type 1 Diabetes. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4427-4440. doi: 10.1210/jc.2019-00481.
• Ho J, Reimer RA, Doulla M, Huang C. Effect of prebiotic intake on gut microbiota, intestinal permeability and glycemic control in children with type 1 diabetes: study protocol for a randomized controlled trial. Trials. 2016 Jul 26;17(1):347. doi: 10.1186/s13063-016-1486-y.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (ACTUAL): June 1, 2018
• Study Completion (ANTICIPATED): December 1, 2019

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: May 12, 2015
• First Posted (ESTIMATE): May 13, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• 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: OFSDM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED