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

Type 1 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04114357
• Other study ID #: 1907172784
• Secondary ID: KL2TR002530UL1TR
• Status: Completed
• Phase: Phase 3
• Start date: June 22, 2020
• Est. completion date: June 9, 2023

Study information

• Verified date: July 2023
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 9, 2023
• Est. primary completion date: June 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 11 Years to 17 Years

Eligibility

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 -

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Acetylated and Butyrylated High Amylose Maize Starch
Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner

Locations

Country	Name	City	State
United States	Indiana University School of Medicine	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in frequency of Mucosal Associated invariant T (MAIT) cells	We will compare changes in MAIT cell frequency before and after the interventions	Through study completion, an average of 12 weeks
Other	Changes in function of Mucosal Associated invariant T (MAIT) cells	We will compare changes in MAIT cell function before and after the interventions	Through study completion, an average of 12 weeks
Other	Changes in phenotype of Mucosal Associated invariant T (MAIT) cells	We will compare changes in MAIT cell phenotype before and after the interventions	Through study completion, an average of 12 weeks
Primary	Change in the gut microbiome profile	We plan to assess the effect of administering HAMS-AB on the gut microbiome profile in people with recently-diagnosed T1D by sequencing the gut microbiome profile.	Through study completion, an average of 12 weeks
Secondary	Changes in the Short Chain Fatty Acid Levels in the Gut.	Measurement of Short Chain Fatty Acid Levels in the Stools.	Through study completion, an average of 12 weeks
Secondary	Changes in Glycemia.	We will compare glycemic changes pre/post intervention with HAMS-AB and between the intervention and control groups. We will measure glycemia using HbA1c, average glucose and glucose variability using blinded continuous glucose monitoring.	Through study completion, an average of 12 weeks
Secondary	Changes in Beta cell Health.	We will compare ß-cell measures pre/post intervention with HAMS-AB and between the intervention and control groups. We will assess ß-cell function using mixed meal tolerance-derived C-peptide measures. We will assess ß-cell stress using fasting proinsulin/C-peptide (PI:C) ratios. We will assess ß-cell death by differential methylation of preproinsulin (INS) DNA.	Through study completion, an average of 12 weeks