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

Phase 3
Completed
Conditions
Type 1 Diabetes
Interventions
Drug: Acetylated and Butyrylated High Amylose Maize Starch
Registration Number
NCT04114357
Lead Sponsor
Indiana University
Brief Summary

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.

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 first to take the supplement or follow a diabetic diet 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
7
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)].
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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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Supplement Intervention and Control Diet, then Control Diet AloneAcetylated and Butyrylated High Amylose Maize StarchThis 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.
Primary Outcome Measures
NameTimeMethod
Change in the Gut Microbiome Profilebefore and after completion of each 4 week sequence

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.

Secondary Outcome Measures
NameTimeMethod
Changes in the Short Chain Fatty Acid Levels in the Gut.before and after completion of each 4 week sequence

Measurement of Short Chain Fatty Acid Levels in the Stools.

Changes in Average Glucosebefore and after completion of each 4 week sequence

We will compare average glucose changes pre/post intervention with HAMS-AB. We will compare their glycemic changes using continuous glucose monitoring data.

C-peptide Levels (Changes in Beta Cell Health).before and after completion of each 4 week sequence

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).

Trial Locations

Locations (1)

Indiana University School of Medicine

🇺🇸

Indianapolis, Indiana, United States

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