Trial Outcomes & Findings for Effect of Prebiotics on the Gut Microbiome Profile and Beta Cell Function (NCT NCT04114357)

NCT ID: NCT04114357

Last Updated: 2024-10-01

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: before and after completion of each 4 week sequence
• Results posted on: 2024-10-01

Participant Flow

Participant milestones

Measure	Supplement Intervention and Control Diet, Then Control Diet Alone This group will first consume the supplement daily for 4 weeks in addition to the control diet and then cross-over to control diet alone. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone, Then Supplement Intervention and Control Diet This arm will start with the control diet alone then cross over to receive the supplement for 4 weeks in addition to the control diet.
Baseline-Randomization STARTED	6	6
Baseline-Randomization COMPLETED	3	4
Baseline-Randomization NOT COMPLETED	3	2
Cross-over STARTED	3	4
Cross-over COMPLETED	3	3
Cross-over NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Supplement Intervention and Control Diet, Then Control Diet Alone This group will first consume the supplement daily for 4 weeks in addition to the control diet and then cross-over to control diet alone. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone, Then Supplement Intervention and Control Diet This arm will start with the control diet alone then cross over to receive the supplement for 4 weeks in addition to the control diet.
Baseline-Randomization Adverse Event	2	1
Baseline-Randomization Lost to Follow-up	1	1
Cross-over Adverse Event	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Intervention Group n=6 Participants 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	Control Group n=6 Participants This arm will not receive the supplement for 4 weeks.	Total n=12 Participants Total of all reporting groups
Age, Continuous	14.98 years STANDARD_DEVIATION 1.92 • n=5 Participants	13.58 years STANDARD_DEVIATION 1.07 • n=7 Participants	14.28 years STANDARD_DEVIATION 1.73 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Supplement Intervention and Control Diet n=5 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=6 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Change in the Gut Microbiome Profile Baseline Bifidobacterium Longum	818.5 species count Interval 110.0 to 1280.0	229 species count Interval 49.0 to 609.0
Change in the Gut Microbiome Profile Bifidobacteria Longum (after 4 weeks)	1610 species count Interval 382.0 to 1819.5	177 species count Interval 75.5 to 924.5
Change in the Gut Microbiome Profile Baseline Parabacteroides distasonis	4964 species count Interval 0.0 to 9782.0	2632 species count Interval 1407.0 to 5179.5
Change in the Gut Microbiome Profile Parabacteroides distasonis (after 4 weeks)	561 species count Interval 55.0 to 3556.0	561 species count Interval 136.0 to 2986.0

SECONDARY outcome

Timeframe: before and after completion of each 4 week sequence

Measurement of Short Chain Fatty Acid Levels in the Stools.

Outcome measures

Measure	Supplement Intervention and Control Diet n=5 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=7 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Changes in the Short Chain Fatty Acid Levels in the Gut. Butyrate	23 mmol / kg fecal material Standard Deviation 6	19 mmol / kg fecal material Standard Deviation 5
Changes in the Short Chain Fatty Acid Levels in the Gut. Propionate	16 mmol / kg fecal material Standard Deviation 9	16 mmol / kg fecal material Standard Deviation 5
Changes in the Short Chain Fatty Acid Levels in the Gut. acetate	60 mmol / kg fecal material Standard Deviation 23	56 mmol / kg fecal material Standard Deviation 18

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Supplement Intervention and Control Diet n=5 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=3 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Changes in Average Glucose baseline	256 mg/dl Standard Deviation 19	228 mg/dl Standard Deviation 13
Changes in Average Glucose 4 weeks after	232 mg/dl Standard Deviation 31	217 mg/dl Standard Deviation 27

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Supplement Intervention and Control Diet n=4 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=3 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
C-peptide Levels (Changes in Beta Cell Health). baseline	2.0 ng/ml Standard Deviation 0.3	1.7 ng/ml Standard Deviation 0.3
C-peptide Levels (Changes in Beta Cell Health). after 4 weeks	2.7 ng/ml Standard Deviation 0.6	2.6 ng/ml Standard Deviation 0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Measure	Supplement Intervention and Control Diet n=7 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=8 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells after 4 weeks	2.1 percentage of CD3 T cells	2.4 percentage of CD3 T cells
Changes in Frequency of Mucosal Associated Invariant T (MAIT) Cells Baseline	2.3 percentage of CD3 T cells	1.6 percentage of CD3 T cells

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Measure	Supplement Intervention and Control Diet n=7 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=8 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Changes in Function of Mucosal Associated Invariant T (MAIT) Cells before	4.7 percentage of MAIT cells	3.8 percentage of MAIT cells
Changes in Function of Mucosal Associated Invariant T (MAIT) Cells after	3.2 percentage of MAIT cells	4.0 percentage of MAIT cells

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Measure	Supplement Intervention and Control Diet n=7 Participants This group will consume the supplement daily for 4 weeks along with following the diabetic diet. Acetylated and Butyrylated High Amylose Maize Starch: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner	Control Diet Alone n=8 Participants This group will only follow the diabetic diet and not receive the supplement for 4 weeks.
Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells before	16.7 percentage of MAIT cells	11.5 percentage of MAIT cells
Changes in Phenotype of Mucosal Associated Invariant T (MAIT) Cells after	5.4 percentage of MAIT cells	9.0 percentage of MAIT cells

Adverse Events

Intervention Group

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Control Group

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Intervention Group n=9 participants at risk 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	Control Group n=10 participants at risk This arm will not receive the supplement for 4 weeks.
Musculoskeletal and connective tissue disorders Dental Pain	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Investigations anxiety	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Infections and infestations bilateral halux infection	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Infections and infestations cold	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders abdominal pain	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Infections and infestations yeast infection	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders flatulence	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders emesis	11.1% 1/9 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	0.00% 0/10 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders constipation	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	20.0% 2/10 • Number of events 2 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Skin and subcutaneous tissue disorders rash at sensor insertion site	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Metabolism and nutrition disorders low vitamin D	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Investigations sweating during blood draw	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 3 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Vascular disorders epistaxis	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Gastrointestinal disorders loss of appetite	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Product Issues CGM fell off	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.
Nervous system disorders Headaches	0.00% 0/9 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.	10.0% 1/10 • Number of events 1 • 12 weeks CTCAE was used for adverse and serious adverse event reporting. Data on AEs was collected at the time of each scheduled visit in addition to in between visit during phone communications.

Additional Information

Heba M Ismail

Indiana University

Phone: 317-278-8326

Email: heismail@iu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place