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

Indiana University

Status and phase: Completed; Phase 1

Conditions: Type 1 Diabetes

Treatments: Drug: Acetylated and Butyrylated High Amylose Maize Starch

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04114357

KL2TR002530 (U.S. NIH Grant/Contract)

1907172784

UL1TR002529 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 11 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Supplement Intervention and Control Diet, then Control Diet Alone

Experimental group

Description:

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.

Treatment:

Drug: Acetylated and Butyrylated High Amylose Maize Starch

Control Diet Alone, then Supplement Intervention and Control Diet

No Intervention group

Description:

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.