Clinical trial NCT04114357: Effect of Prebiotics on the Gut Microbiome Profile and Beta Cell Function
Official title: Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and Beta Cell Function in Newly Diagnosed Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2019-10-03
Enrollment: 12
Sex: ALL
Minimum age (years): 11
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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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Primary outcomes:
measure: Change in the Gut Microbiome Profile
timeFrame: before and after completion of each 4 week sequence
Secondary outcomes:
measure: Changes in the Short Chain Fatty Acid Levels in the Gut.
timeFrame: before and after completion of each 4 week sequence
measure: Changes in Average Glucose
timeFrame: before and after completion of each 4 week sequence
measure: C-peptide Levels (Changes in Beta Cell Health).
timeFrame: before and after completion of each 4 week sequence
Other outcomes:
measure: Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells
timeFrame: before and after completion of each 4 week sequence
measure: Changes in Function of Mucosal Associated Invariant T (MAIT) Cells
timeFrame: before and after completion of each 4 week sequence
measure: Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells
timeFrame: before and after completion of each 4 week sequence
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
Study officials:
References: