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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04114357

Enrollment

Registered

2019-10-03

Start date

2020-06-22

Completion date

2023-06-09

Last updated

2024-10-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes

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.

Interventions

DRUGAcetylated and Butyrylated High Amylose Maize Starch

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

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

11 Years to 17 Years

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 \-

Design outcomes

Primary

Measure	Time frame	Description
Change in the Gut Microbiome Profile	before 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

Measure	Time frame	Description
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 Glucose	before 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).

Other

Measure	Time frame	Description
Changes in Function of Mucosal Associated Invariant T (MAIT) Cells	before and after completion of each 4 week sequence	We will compare changes in % of MAIT cell with CD25 function before and after the interventions
Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells	before and after completion of each 4 week sequence	We will compare changes in % of MAIT cells with a BCL2-GzB+ phenotype before and after the interventions
Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells	before and after completion of each 4 week sequence	We will compare changes in MAIT cell frequency (as measured by % of CD3 T cells that are MAIT cells) before and after the interventions

Countries

United States

Participant flow

Participants by arm

Arm	Count
Intervention Group This arm will consume the supplement daily for 4 weeks. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	6
Control Group This arm will not receive the supplement for 4 weeks.	6
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Baseline-Randomization	Adverse Event	2	1
Baseline-Randomization	Lost to Follow-up	1	1
Cross-over	Adverse Event	0	1

Baseline characteristics

Characteristic	Intervention Group	Total	Control Group
Age, Continuous	14.98 years STANDARD_DEVIATION 1.92	14.28 years STANDARD_DEVIATION 1.73	13.58 years STANDARD_DEVIATION 1.07
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	7 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants	5 Participants	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	5 Participants	10 Participants	5 Participants
Region of Enrollment United States	6 participants	12 participants	6 participants
Sex: Female, Male Female	6 Participants	10 Participants	4 Participants
Sex: Female, Male Male	0 Participants	2 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 9	0 / 10
other Total, other adverse events	7 / 9	7 / 10
serious Total, serious adverse events	0 / 9	0 / 10

Outcome results

Primary

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.