Effect of Prebiotics on the Gut Microbiome Profile and Beta Cell Function

Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and Beta Cell Function in Newly Diagnosed Type 1 Diabetes

Data suggest that intestinal microbiota might be critically involved both in autoimmunity and in glucose homeostasis. An acetylated and butyrylated form of high amylose maize starch (HAMS-AB) that increases beneficial short chain fatty acid (SCFA) production has been safe and effective in disease prevention in mouse type 1 diabetes (T1D) models. The objective of this application is to assess the effect of administering a prebiotic, such as HAMS- AB, on the gut microbiome profile, glycemia and β-cell function in humans with T1D.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Acetylated and Butyrylated High Amylose Maize Starch

Detailed Description

This is a pilot, single center clinical trial to evaluate the effect of using the prebiotic, HAMS-AB, on the gut microbiome profile, glycemia and β-cell function in children and adolescents ages 12-16 years with recently diagnosed type 1 diabetes.

Approximately 12 participants will be randomized to first to take the supplement and follow the diabetic diet or follow a diabetic diet alone for 4 weeks and then cross-over after a 4 week washout period.

The primary objective is to determine the effect of using the prebiotic on the gut microbiome profile in youth with T1D.

The secondary objectives are to determine the effect of using the prebiotic on SCFA production, glycemia and β-cell health and function.

Exploratory outcomes include changes in MAIT cells.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 13 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be between 11-17 years of age
• Willing to consume HAMS-AB and follow a diabetic diet
• Diagnosed by American Diabetes Association criteria with T1D in the last 4-36 months
• Random non-fasting C-peptide of 0.17nmol/ml or greater
• Willing to use an effective form of contraception if sexually active
• BMI< 85% for age and sex
• Positive for any one of the following diabetes-related autoantibodies that are tested clinically [insulin autoantibody (if tested within 14 days of diagnosis), glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 (IA-2), or Zinc transporter 8 autoantibodies (ZnT8)].

Exclusion Criteria:

1. Presence of severe, active disease that interferes with dietary intake or requires the use of chronic medication, except for well-controlled hypothyroidism and mild asthma not requiring oral steroids.
2. Diabetes other than T1D (Known monogenic forms of diabetes, Type 2 diabetes)
3. Chronic illness known to affect glucose metabolism (e.g. Cushing syndrome, polycystic ovarian disorder, cystic fibrosis) or taking medications that affect glucose metabolism (e.g. steroids, metformin)
4. Psychiatric impairment or current use of anti-psychotic medication
5. Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
6. Female participants of child-bearing age with reproductive potential, must not be pregnant and agree to use an effective form of birth control or be abstinent during the study period (see below)
7. History of recurrent infections
8. History of on-going infections or antibiotic treatment within the past three months
9. History of immune compromise
10. Steroid intake (inhaled or oral)
11. Other immunosuppressant use in past 6 months
12. History of gastrointestinal disease
13. Possible or confirmed celiac disease
14. Pregnancy or possible pregnancy
15. Allergy to corn (prebiotic)
16. Allergy to milk or milk products or soy present in Boost
17. Participation in other intervention research trials within the past 3 months
18. Anticipate major changes in diabetes management during study (change from injection to pump, new start of continuous glucose monitoring)
19. Consuming high fiber or vegetarian diet (consuming three or more servings of high fiber foods on 4 or more days per week) using validated dietary assessments (see below under schedule of events table).

20. Taking fiber supplements

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplement Intervention and Control Diet, then Control Diet Alone; This group will first consume the supplement daily for 4 weeks in addition to the diabetic diet then cross-over to follow the diabetic diet for 4 weeks.	Drug: Acetylated and Butyrylated High Amylose Maize Starch; Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner for 4 weeks; Other Names: Hylon™ VII Butyrate, Hylon™ VII Acetate
No Intervention: Control Diet Alone, then Supplement Intervention and Control Diet; This group will follow the control diet for 4 weeks first then cross-over to receive the supplement for 4 weeks in addition to the diabetic diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Gut Microbiome Profile	We planned to assess the effect of administering acetylated and butyrylated high amylose maize starch (HAMS-AB) on the gut microbiome profile in people with recently-diagnosed type 1 diabetes (T1D) by sequencing the gut microbiome profile. This measure was assesed using the absolute abundance of certain bacterial species of interest. The changes will be compared before and after each 4 week time period.	before and after completion of each 4 week sequence

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Short Chain Fatty Acid Levels in the Gut.	Measurement of Short Chain Fatty Acid Levels in the Stools.	before and after completion of each 4 week sequence
Changes in Average Glucose	We will compare average glucose changes pre/post intervention with HAMS-AB. We will compare their glycemic changes using continuous glucose monitoring data.	before and after completion of each 4 week sequence
C-peptide Levels (Changes in Beta Cell Health).	We will compare β-cell measures pre/post intervention with HAMS-AB and between the intervention and control groups. We will assess β-cell function using mixed meal tolerance-derived C-peptide measurements ( a measure of β-cell function).	before and after completion of each 4 week sequence

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells	We will compare changes in MAIT cell frequency (as measured by % of CD3 T cells that are MAIT cells) before and after the interventions	before and after completion of each 4 week sequence
Changes in Function of Mucosal Associated Invariant T (MAIT) Cells	We will compare changes in % of MAIT cell with CD25 function before and after the interventions	before and after completion of each 4 week sequence
Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells	We will compare changes in % of MAIT cells with a BCL2-GzB+ phenotype before and after the interventions	before and after completion of each 4 week sequence

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2020
• Primary Completion (Actual): June 9, 2023
• Study Completion (Actual): June 9, 2023

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 16, 2024
• Last Verified: September 1, 2024

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: 1907172784; UL1TR002529 (U.S. NIH Grant/Contract); KL2TR002530 (U.S. NIH Grant/Contract)

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