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

NCT04114357 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 1907172784KL2TR002530UL1TR002529
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Changes in the Short Chain Fatty Acid Levels in the Gut.

  before and after completion of each 4 week sequence

• Changes in Average Glucose

  before and after completion of each 4 week sequence

• C-peptide Levels (Changes in Beta Cell Health).

  before and after completion of each 4 week sequence

Other Outcomes (3)

• Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells

  before and after completion of each 4 week sequence

• Changes in Function of Mucosal Associated Invariant T (MAIT) Cells

  before and after completion of each 4 week sequence

• Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells

  before and after completion of each 4 week sequence

Study Arms (2)

Supplement Intervention and Control Diet, then Control Diet Alone

EXPERIMENTAL

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

Control Diet Alone, then Supplement Intervention and Control Diet

NO INTERVENTION

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.

Interventions

Acetylated and Butyrylated High Amylose Maize Starch DRUG

Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner for 4 weeks

Also known as: Hylon™ VII Butyrate, Hylon™ VII Acetate

Supplement Intervention and Control Diet, then Control Diet Alone

Eligibility Criteria

• Age: 11 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 \[insulin autoantibody (if tested within 14 days of diagnosis), glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 (IA-2), or Zinc transporter 8 autoantibodies (ZnT8)\].

You may not qualify if:

• 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.
• Diabetes other than T1D (Known monogenic forms of diabetes, Type 2 diabetes)
• 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)
• Psychiatric impairment or current use of anti-psychotic medication
• Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
• 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)
• History of recurrent infections
• History of on-going infections or antibiotic treatment within the past three months
• History of immune compromise
• Steroid intake (inhaled or oral)
• Other immunosuppressant use in past 6 months
• History of gastrointestinal disease
• Possible or confirmed celiac disease
• Pregnancy or possible pregnancy
• Allergy to corn (prebiotic)

Sponsors & Collaborators

• Indiana University: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Related Publications (1)

• Ismail HM, Spall M, Evans-Molina C, DiMeglio LA. Evaluating the effect of prebiotics on the gut microbiome profile and beta cell function in youth with newly diagnosed type 1 diabetes: protocol of a pilot randomized controlled trial. Pilot Feasibility Stud. 2023 Aug 25;9(1):150. doi: 10.1186/s40814-023-01373-4.

  PMID: 37626387 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Heba M Ismail
• Organization: Indiana University

heismail@iu.edu

317-278-8326

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: September 30, 2019
• First Posted: October 3, 2019
• Study Start: June 22, 2020
• Primary Completion: June 9, 2023
• Study Completion: June 9, 2023
• Last Updated: October 1, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)