Clinical trial NCT04114357
Conditions: Type 1 Diabetes
Sponsor: Indiana University
Start date: 2020-06-22; Completion date: 2023-06-09
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Arms: arm 1: 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. arm 2: 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: intervention 1: Acetylated and Butyrylated High Amylose Maize Starch
Intervention descriptions: intervention 1: Participants will be instructed to consume HAMS-AB in two divided doses at breakfast and dinner for 4 weeks

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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Title: Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell 
Function in Newly Diagnosed Type 1 Diabetes 
 
NCT: 04114357 
 
Last Approval Date: April 11th, 2023 
 
 


 
 
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Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell Function in 
Newly Diagnosed Type 1 Diabetes 
 
Version 12.0 (April 2023) 
 
 
NCT# 04114357 
 
 
 
Protocol Physician 
 
Heba Ismail, MB Bch 
Assistant Professor of Pediatrics, Endocrinology and Diabetology, 
Indiana University School of Medicine, Indianapolis 
635 Barnhill Drive, Van Nunys Medical 
Sciences BuildingMS2053Indianapolis, IN 
46202 
Tel: 317-278-7041 
Fax: 317-944-3882 
Email: heismail@iu.edu 
 
 
This clinical study is supported by the KL2 program, the IU Health Values Funds and conducted at Indiana University, 
Indianapolis 


 
 
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TABLE OF CONTENTS: Overview and BACKGROUND 
4 
1.1 
Background .................................................................................................................................................. 4 
1.2 
Overview ...................................................................................................................................................... 4 
1.3 
Preclinical and Clinical Experience .......................................................................................................... 5 
1.4 
Scientific Rationale ...................................................................................................................................... 7 
2.0 
OBJECTIVES ...................................................................................................................... 7 
2.1 
PRIMARY OBJECTIVE .................................................................................................................................. 7 
2.2 
SECONDARY OBJECTIVES .......................................................................................................................... 7 
3.0 
STUDY DESIGN .................................................................................................................. 7 
3.1 
STUDY DESCRIPTION ................................................................................................................................. 7 
3.2 
STUDY DURATION ...................................................................................................................................... 8 
3.3 
ENROLLMENT .............................................................................................................................................. 8 
3.4 
STUDY ENDPOINTS ..................................................................................................................................... 8 
3.5 
ONGOING SAFETY REVIEW ...................................................................................................................... 8 
3.6 
STUDY RISKS ................................................................................................................................................ 9 
3.7 
STUDY BENEFITS ......................................................................................................................................... 9 
3.8 
INCLUSION OF CHILDREN ......................................................................................................................... 9 
4.0 
STUDY SUPPLEMENT ......................................................................................................... 9 
4.1 
STRUCTURE AND NOMENCLATURE ......................................................................................................... 9 
4.2 
PHYSICAL ANDCHEMICAL PROPERTIES .................................................................................................... 9 
4.3 
STABILITY AND REACTIVITY .................................................................................................................. 10 
4.4 
CLINICAL STUDIES –MECHANISM OF ACTION .................................................................................... 10 
4.5 
STUDY RELATION INFORMATION .......................................................................................................... 10 
5.0 
ELIGIBILITY ..................................................................................................................... 10 
5.1 
INCLUSION CRITERIA ............................................................................................................................... 10 
5.2 
EXCLUSION CRITERIA .............................................................................................................................. 11 
5.3 
EARLY TERMINATION OF ASTUDY PATIENT ....................................................................................... 11 
6.0 
STUDY PROCEDURES ........................................................................................................ 12 
6.1 
STUDY DESIGN .......................................................................................................................................... 12 
6.2 
RANDOM ASSIGNMENT ........................................................................................................................... 12 
6.3 
SCHEDULE OF EVENTS ............................................................................................................................ 13 
6.4 
STUDY VISITS ............................................................................................................................................. 15 
6.5 
ONGOING DIABETES MANAGEMENT ................................................................................................... 17 
6.6 
BANKED SPECIMENS ................................................................................................................................ 17 
7.0 
REPORTING OF ADVERSE EVENTS OR UNANTICIPATED PROBLEMS INVOLVING 
RISK TO PARTICIPANTS OR OTHERS ................................................................................. 17 
7.1 
UNANTICIPATED PROBLEMS ................................................................................................................... 17 
7.2 
DATA SAFETY MONITORING BOARD .................................................................................................... 18 
7.3 
ADVERSE EVENTS ..................................................................................................................................... 18 
8.0 
STATISTICAL CONSIDERATIONS ........................................................................................ 19 
9.0 
PRIVACY/CONFIDENTIALITY ISSUES ................................................................................ 19 
10.0 
FOLLOW-UP AND RECORD RETENTION ............................................................................ 19 
10.1 
RECORD RETENTION ................................................................................................................................ 19 
11.0 
REFERENCES CITED .................................................................................................... 19-21 


 
 
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1.0 – OVERVIEW AND BACKGROUND 
 
1.1 
BACKGROUND 
 
Type 1 diabetes (T1D) is a disease characterized by progressive β-cell loss with eventual dependence on exogenous 
insulin. The incidence of T1D is rising at a rate of nearly 3% per year, and the disease contributes over $14.4 
billion annually to U.S. healthcare expenditures [1, 2]. While immunomodulatory therapy administered near the 
time of clinical diagnosis has shown some efficacy in attenuating T1D progression, the long-term effectiveness of 
these drugs has been negligible [3-7]. Given these failures, there is a critical need for a simple, tolerable, cost- 
effective method to mitigate the disease process and burden associated with daily diabetes management. 
 
Compared to healthy individuals, people with both type 1 and type 2 diabetes demonstrate gut dysbiosis (microbial 
imbalance) with a higher gram-negative to gram-positive gut bacterial ratio (creating a pro-inflammatory milieu) 
and fewer bifidobacteria, an important microbial population associated with many health benefits [8-13]. Further, 
the gut microbiome composition of T1D children shows increased virulence factors, phage, prophage, motility 
genes and higher response to stress [14-18], in addition to a lower count of bacteria producing butyrate, a short 
chain fatty acid (SCFA) with anti-inflammatory actions [19]. 
 
The effect of gut microbiome modulation on glycemia has been assessed using both prebiotics (supplements 
containing substrates for the microbiota) and probiotics (supplements containing microbiota). Animal studies 
have shown that pre and probiotic use can change the gut microbiome profile, modulate the immune system, and 
improve glucose tolerance [20-22]. In persons with type 2 diabetes (T2D), prebiotics improve hemoglobin A1c 
(HbA1c) and postprandial glycemic excursion as well as reduce insulin resistance [23-26]. Thus, it appears that 
altering the gut microbiome may improve glycemia and improve insulin sensitivity. 
 
A novel approach to mitigating T1D is perturbation of the gut microbiome using high-amylose maize starch 
(HAMS), a well-tolerated source of dietary fiber with selective fermentation properties. HAMS consumption shifts 
the gut microbiome profile towards SCFA fermenters. Further, HAMS that is acetylated and butyrylated (HAMS- 
AB) releases large amounts of beneficial SCFAs after colonic bacterial fermentation. Indeed, recent T1D mouse 
studies [22] have shown that HAMS-AB feeding shifted the gut microbiome profile towards fermenters, resulting 
in higher blood and fecal concentrations of the microbial metabolites acetate and butyrate (both beneficial SCFAs). 
These changes were associated with lower rates of progression to T1D, lower circulating inflammatory marker 
concentrations, and less islet autoimmunity. Data to date using HAMS in humans are more limited. When given to 
non-diabetic adults, HAMS lowers post-prandial glucose production and improves insulin sensitivity [27, 28]. 
 
1.2 Overview 
Given these promising findings in animal models of T1D as well as adult non-diabetic studies, we hypothesize 
that HAMS-AB will alter the gut microbiome profile in humans with T1D and increase SCFA production and 
that these changes will be associated with improved β-cell function, overall glycemia, and β-cell health (as measured 
by markers of β-cell stress and death). We plan to perform a pilot, randomized, controlled cross-over trial of 
HAMS-AB in 12 individuals with recently diagnosed T1D to determine HAMS-AB effects on the gut microbiome 
profile, SCFA production, glycemia, markers of β-cell function, stress, and death. 
 
This pilot study is a single center trial. Twelve newly diagnosed T1D youths with a BMI<85% and within 4-36 
months of diagnosis who have measurable endogenous insulin production, assessed using serum C-peptide, and 
are, therefore, in the honeymoon period, will be recruited. We have chosen this cohort since the microbiome 
profile differs by age [29] and BMI [30], and the progression of T1D differs between children and adults [31]. 
Additionally, there is ample published experience studying healthy adolescents and their microbiome changes with 
corn fiber supplementation [32, 33], and therefore, we have chosen to pilot this intervention in a similar age group 
with known published data. In addition, to assess changes more accurately in β-cell function, we will include those 
in the honeymoon period as there is sufficient measurable C- peptide secretion during this time. The honeymoon 
period is the time shortly after T1D diagnosis when the β-cells undergo partial and temporary recovery and 
produce enough insulin to reduce insulin needs and aid with glycemic control [34, 35]. 


 
 
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The objectives of this study are to assess the HAMS-AB effects on the gut microbiome profile, SCFA production, 
glycemia and β-cell health and function in humans with T1D. We hypothesize that HAMS-AB will (i) improve 
the gut microbiome profile in humans with T1D, (ii) increase SCFA production, and (iii) improve β-cell function, 
β-cell health and overall glycemia. We propose the following Specific Aims: 
 
AIM 1: Determine the effect of HAMS-AB on the gut microbiome profile and SCFA production in 
children with recently diagnosed T1D. We hypothesize that HAMS-AB consumption will shift the gut 
microbiome to microbial populations that are capable of HAMS-AB fermentation and increase SCFA production. 
Twelve youths (11-17 years old) will consume HAMS-AB or follow the standard of care recommended diabetic 
diet daily for [49,50] 4 weeks and then cross over after a 4-week washout period. DNA will be extracted from 
fecal samples obtained followed by 16S RNA sequencing for gut microbial community analysis at baseline and at 
each visit during the study period [32, 33]. SCFAs will be analyzed using standard methods [36, 37].  
AIM 2: Determine the effect of HAMS-AB on glycemia and β-cell function and health. We hypothesize that 
the prebiotic HAMS-AB will improve overall glycemia including reducing glycemic variability in recently 
diagnosed persons with T1D. We will compare glycemic/ β-cell measures 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 continuous glucose monitoring (CGM) [38-40]. We expect to see an improvement in 
glycemia in response to HAMS-AB intake. We will assess β-cell function using mixed meal tolerance (MMTT)- 
derived C-peptide measures. We expect that measures of β-cell stress/death will show improvement following the 
use of HAMS-AB. We will determine β-cell stress using proinsulin/C-peptide (PI:C) ratios [41]. We will assess β-
cell death by differential methylation of preproinsulin (INS) DNA [42]. 
 
Upon successful completion of this pilot study, we expect to assess the effect of prebiotic administration on the 
gut microbiome profile, SCFA production, glycemia and β-cell function in humans with T1D. The knowledge 
generated by the proposed research will provide critical experimental information needed to substantiate a fully 
powered study. 
 
1.3 
PRECLINICAL AND CLINICAL EXPERIENCE 
 
HAMS is a prebiotic that is a well-tolerated source of dietary fiber with selective fermentation properties. In T1D 
mouse studies [21], feeding HAMS that has been acetylated and butyrylated (HAMSA and HAMSB) shifts the gut 
microbiome profile towards fermenters, resulting in increased acetate and butyrate production and lower rates of 
progression to T1D, Figure 1. 
 
In a human study assessing the effects of 2 levels of intake of HAMS [15 or 30 g/d (double-blind)] compared to 
control starch intake (0 HAMS) for 4-wk periods separated by 3-wk washouts on insulin sensitivity (SI) in 
participants with increased waist circumference, it appeared that the consumption of 15–30 g/d of HAMS 
improved insulin sensitivity significantly in men, Figure 2 [27]. 
 
In another human randomized, double-blind, controlled study [28] in healthy adults who consumed either a high 
fiber scone containing a novel chemically modified high amylose maize starch or a low fiber control scone without 
the maize starch, the consumption of the high fiber scone significantly reduced postprandial glucose and insulin 
incremental areas under the curves (43–45% reduction, 35–40% reduction, respectively) and postprandial glucose 
and insulin maximum concentrations (8–10% and 22% reduction, respectively), Figure 3. Of note, ingestion of 
the high fiber scone consumption was not associated with increased gastrointestinal side effects compared with 
the control scone. 


 
 
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Figure1: Incidence of T1D in female 
NOD mice fed the NP diet (n = 25 
mice), HAMS diet (n = 17 mice), 
HAMSA diet (n = 11 mice), HAMSB 
diet (n = 12 mice) or combined 
(HAMSA plus HAMSB) diet (n = 11 
mice) for 10 weeks (HAMSA plus 
HAMSB; orange arrows) or 5 weeks (all 
other diets; blue arrows), starting at 5 
weeks of age. NS (NP vs HAMS, 
HAMSB vs HAMS, HAMSP vs 
HAMS, and HAMSP vs NP); *P = 
0.0482 (HAMSB vs NP), #P = 0.0490 
(HAMSA vs HAMS), **P = 0.0069 
(HAMSA vs NP), ##P = 0.0025 
(HAMSA+HAMSB   vs   HAMS) and 
***P = 0.0008 (HAMSA+HAMSB vs 
NP) (Mantel-Cox log-rank test) [22]. 
 
Conventional, 
non-purified 
(NP), 
High-amylose maize starch (HAMS) 
that has been acetylated (HAMSA) or 
butyrylated (HAMSB), non-significant 
(NS). 
 
 
 
Figure 2: Insulin sensitivity (SI) following 4-wk feeding periods for control (0 g/d HAMS), 15 g/d HAMS, and 30 
g/d HAMS in men (n = 11) and women (n = 22). Bars represent least squares geometric means and error bars 
extend to the value of the loge least squares mean + 1 SEM, back transformed to the original units. Labeled means 
without a common letter differ, P < 0.05. Least squares mean and SEM values for loge SI were generated from 
repeated-measures ANOVA models containing terms for participant as a random variable, treatment condition, 
treatment sequence, and measures of insulin sensitivity [27]. 
 
 


 
 
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Figure 3: Mean post-prandial glucose and insulin 
concentrations over 180 min after ingestion of a scone 
containing a chemically modified maize resistant starch: 
a. venous glucose, b. capillary glucose, c. venous insulin. 
Error bars represent the standard error of the mean [28]. 
 
1.4 
SCIENTIFIC RATIONALE 
 
To date, there have been no studies assessing the effect of 
using a prebiotic, such as HAMS-AB, on the gut 
microbiome profile, glycemia and β-cell function in humans 
with T1D. In addition, there are no data linking changes in 
the gut microbiome and their metabolites in response to 
administration of HAMS-AB to metabolic changes in 
youths with T1D. This study will examine repurposing an 
existing, safe supplemental product for the treatment of 
T1D. 
 
2.0 – OBJECTIVES 
 
2.1 
Primary Objective 
 
Assess the effect of administering HAMS-AB on 
the gut microbiome profile in people with 
recently diagnosed T1D. 
 
2.2 Secondary Objectives 
 
Assess the effect of administering HAMS-AB on 
SCFA production in people with recently- 
diagnosed T1D. 
Determine the effect of HAMS-AB on glycemia 
and β-cell function and health. 
 
3.0 – STUDY DESIGN 
 
3.1 
STUDY DESCRIPTION 
 
This study will be a single center, controlled, randomized trial in young individuals newly diagnosed with type 
1 diabetes. We are enrolling youth with new onset T1D with documented continued residual C-peptide 
production. Within 30 days of screening during which eligibility will be determined, subjects will have a 4-week 
treatment period with HAMS-AB or will be provided with guidelines on the generally recommended diabetic 
diet for youths with T1D [49, 50]. After a 4-week wash-out period the durability of effect will be assessed in 
those who received the prebiotic and during this washout period, both the study and control arm will be 
permitted to consume a regular diet. This design has been used in other studies of prebiotic administration with 
a 3–4-week intervention period and a 3–4-week washout phase [21, 32, 33]. Subjects will then cross over to either 
HAMS-AB or diet control for another 4 weeks. 
 
A full dosing description can be found in section 6.2. 


 
 
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3.2 
STUDY DURATION 
 
This study will screen up to 24 subjects at a single center (see Enrollment below). 12 subjects will be enrolled 
after meeting all eligibility criteria. If at any time during the study, a participant does not meet eligibility, 
participation in the study will be on hold until subject meets all eligibility criteria again. Participants may re-
enter or re-enroll in the study if in the future, meet all eligibility requirements. Participants who re-enter or re-
enroll will need to be reassessed for their starting point. Subjects who miss 20% of prebiotic doses (11 of 56 
doses) will be replaced. The study will include the following periods: 
 
• 
(1) Screening visit and eligibility determination (up to 30 days). 
• 
(2) 4-week intervention period or diet guideline 
• 
(3) 4-week washout period 
• 
(4) 4-week intervention period or diet guideline. 
 
3.3 
ENROLLMENT 
 
Up to 24 subjects will be screened to find 12 adequate subjects eligible for enrollment. 
 
The plan is to recruit 24 patients with the goal of having 50% eligible and enrolled. Once 12 participants have 
completed the 12 week visit, we will stop recruitment. At Indiana University, as per our current recruitment 
strategies for other new-onset studies, patients with newly diagnosed T1D will be approached whenever possible 
when inpatient at diagnosis and then re-contacted after discharged home. Visits will be conducted at the Indiana 
Clinical Research Center (ICRC) and coordinated with diabetes clinic follow-up visits when possible. 
 
3.4 
STUDY ENDPOINTS 
 
The primary outcome assessment will be to assess changes in the gut microbiome profile in response to HAMS- 
AB. Secondary outcome measures will be changes in SCFA production, changes in glycemia, pro-insulin to C- 
peptide ratios as a marker of β cell ER stress. Other β cell stress markers including unmethlyated insulin DNA will 
also be measured. We will also examine glycemic outcomes and β cell function as assessed by responses to MMTT, 
although given the variability in these measures in other reported studies of new-onset T1D [43] we do not expect 
to be adequately powered in this small trial to see significant differences in these outcomes. 
 
3.5 
STUDY RISKS 
 
Risks include those risks related to taking HAMS-AB, having blood draws, mixed meal tolerance tests (MMTT), risk 
of CGM use, and the possible loss of confidentiality. 
 
Risks of Taking HAMS-AB: 
Given that most youths in the United States are consuming less than the recommended dietary intake of fiber, we 
anticipate the following risks: 
• 
Likely (reported in >20% of patients): initial abdominal discomfort, increase in frequency of bowel 
movements, although not to the extent of causing diarrhea. These mild intestinal symptoms will likely last 
for only the first few days and are self-limited without intervention. 
 
Risk of Blood Draws: 
The insertion of a needle can cause some local pain and can result in bruising. Blood draws can in rare instances 
cause lightheadedness or fainting. There is also a risk of infection. To mitigate these risks, blood draws will be 
performed by trained technicians or nurses using standard aseptic techniques. 
 
Risk of MMTT: 
There are no known risks to an MMTT, but the taste of the Boost may not be well tolerated. Some persons may 
experience nausea after drinking Boost. Subjects with milk or soy allergies will be excluded to avoid any allergic 


 
 
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reactions to Boost. If the blood glucose is high at the end of the test, subjects will be instructed to give an insulin 
correction dose. 
 
Risks related to CGM use: 
The CGM/sensor may produce pain when it is inserted into the skin. There is a low risk for developing a local skin 
infection at the site of the sensor needle placement. Itchiness, redness, bleeding, and bruising at the insertion site may 
occur as well as local tape allergies. 
 
Loss of Confidentiality: 
There is the unlikely chance that health information is viewed by someone outside of the research team who is 
not authorized to see health information. All files will be kept in locked cabinets within a locked room. Any 
electronic data will be protected by password systems. 
 
3.6 
STUDY BENEFITS 
 
While receiving HAMS-AB, there are potential benefits in reduction of β-cell stress for these patients. Since the 
gut dysbiosis may be important in the pathogenesis of T1D, accentuate β-cell stress, and have a role in the 
complications of the disease, these studies are of scientific importance. The benefits to be derived by mankind 
are expected to be substantial and may lead to advances in the prediction, prevention, and treatment of type 1 
diabetes. If this study indicates that treatment can safely preserve beta cell health, then it will be a major advance 
in the care of diabetes. 
 
3.7 
INCLUSION OF CHILDREN 
 
Type 1 diabetes is a disease that typically has its onset in children, adolescents, and young adults. Because we 
are interested in examining the role of the HAMS-AB and the gut microbiome in adolescents with T1D (and 
potentially eventually those at risk for developing T1D), adolescents will be studied to have data in a relevant 
population. As part of the consent process, in addition to consent from the parent, assent for studies and 
samples from all participants will be obtained. 
 
4.0 – STUDY SUPPLEMENT 
 
4.1 
STRUCTURE AND NOMENCLATURE 
CAS Registry No.: 
none 
Chemical Name: 
high amylose maize starch 
Chemical Family: 
Starch 
Molecular Weight: 
>1000 
Synonyms: 
HYLON® VII 
 
4.2 
PHYSICAL AND CHEMICAL PROPERTIES 
Pure Substance or 
Mixture: 
Pure 
Appearance (physical 
state): 
Powder. 
Color: 
White 
Odor: 
Starch 
Odor threshold: 
Not available 
Molecular Weight: 
> 10000 
pH: 
Not available 
pH in (1%) Solution: 
Approximately 5.5 
Melting 
Point/Freezing Point 
(°C): 
Not available 
Relative Density: 
Not available 


 
 
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Specific Gravity 
1.5 
Solubility(ies) in Water: 
Insoluble 
 
 


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4.3 STABILITY AND REACTIVITY 
 
Reactivity: 
Not expected to be reactive 
Chemical stability: 
Material is stable under normal temperatures and 
pressures. 
Possibility of hazardous reactions: 
Hazardous polymerization will not occur. 
Conditions to avoid (e.g., static discharge, 
shock, or vibration): 
None known 
Incompatible materials: 
None known 
Hazardous decomposition products: 
This product does not undergo spontaneous 
decomposition. Typical combustion products are 
carbon monoxide, carbon dioxide, nitrogen, and water. 
 
4.4 
CLINICAL STUDIES – MECHANISM OF ACTION 
 
HAMS appears to work by altering the gut microbiome profile and improving glycemia and insulin 
sensitivity [26, 27]. Additionally, the FDA has concluded that there was scientific evidence for a qualified 
health claim that HAMS reduced risk of type 2 diabetes development in adults. 
 
 
4.5 
STUDY RELATED INFORMATION 
 
HAMS-AB will be in the form of acetylated and butyrylated HYLON® VII corn starch [a resistant corn 
starch type 2 (RS2) derived from high amylose maize starch and containing approximately 70% amylose 
that has been acetylated and butyrylated. It will be provided by Ingredion Incorporated, Bridgewater, NJ. A 
computer-based randomization plan will be prepared by the PI. Randomization lists will be kept by the PI. 
 
HAMS is a resistant corn starch type 2 dietary supplement which is high in certain foods such as potatoes 
and green unripe bananas. RS2 is not digested in the small intestine and acts as a dietary fiber. Many short 
chain fatty acids (SCFAs), including acetic, propionic, and butyric acid, are formed normally during bacterial 
fermentation in the gut after fiber intake. Therefore, there are no expected adverse effects in general. Similarly, 
we do not expect any adverse effects during pregnancy. However, to be safe, female subjects who are pregnant 
or anticipating pregnancy will not be enrolled and pregnancy tests will be done for females of reproductive 
potential at all visits. 
 
HAMS has a satisfactory safety profile based on exposure in adults and pediatrics given that it is a dietary 
supplement available over the counter. To date, there has been no indication of specific organ class toxicity. 
Additionally, there has been no indication of a particular pattern of event clustering or increased individual 
safety risk, and no increased vulnerabilities or major risks have been identified for the T1D and pediatric 
population. 
 
5.0 – ELIGIBILITY 
 
5.1 
INCLUSION CRITERIA 
Patients must meet all the following criteria: 
• 
Be between 11-17 years of age 
• 
Willing to consume HAMS-AB and follow a diabetic diet 
• 
Diagnosed by ADA criteria [45] with T1D in the last 4-36 months 
• 
Random non-fasting C-peptide of 0.17nmol/L or greater 
• 
Willing to use an effective form of contraception if sexually active 


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• 
BMI< 85% for age and sex 
• 
Positive for any one of the following diabetes-related autoantibodies that are tested 
clinically [IAA (if tested within 14 days of diagnosis), GAD, IA-2, or ZnT8]. 
 
5.2 
EXCLUSION CRITERIA 
Individuals who meet any of the exclusion criteria during the study will be replaced. However, participants 
may re-enroll if in the future, meet all eligibility requirements. Participants who re-enroll will need to be 
reassessed for their starting point. Participants must NOT meet any of the following criteria during enrollment 
re-entry or re-enrollment: 
1. 
Presence of severe, active disease that interferes with dietary intake or requires the use of chronic 
medication, with the exception of 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 4-6 weeks 
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, start of CGM usage if not already using one) 
19. 
Consuming high fiber or vegetarian diet (consuming three or more servings of high fiber foods 
on 4 or more days per week) by history. 
20. 
If taking fiber supplements or probiotics, unwilling to stop for the duration of the study. 
 
Although generally considered to be safe, this has not been specifically studied in pregnant women and therefore, 
females of childbearing age will be asked to use effective Forms of Birth Control – any one of the following 
(additionally, participants will be counseled on the use of a second method of contraception): 
a. 
Use of oral, injected, or implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy (failure rate <1%), for example, hormone 
vaginal ring or transdermal hormone contraception 
b. 
Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
c. 
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/vaginal suppository 
5.3 EARLY TERMINATION OF A STUDY PARTICIPANT 
 
Treatment will stop and the subject will return for an exit visit if any of the following conditions occur: 
• withdrawal of consent 
• pregnancy (female participants) 
• any medically important event such as a concurrent illness or complications 


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• any investigator judgment 
6.0 – STUDY PROCEDURES 
6.1 STUDY DESIGN 
 
 
6.2 
RANDOM ASSIGNMENT 
 
Subjects will be randomly assigned (6 in each arm) to either HAMS-AB plus a recommended diabetic diet or 
control diabetic diet alone [49, 50] for the first 4 week of treatment period. After a suitable washout period 
during which participants do not need to follow the recommended diet or use the supplement, subjects will 
continue for 4 weeks after a cross-over. All participants will be expected to follow the guidelines for a healthy 
diabetic diet during the study period, except for during the 4-week washout period. 
 
A computer-based randomization plan will be prepared by the principal investigator. The document will be 
kept by the study team for use. As a subject is screened and qualifies, he/she will be assigned in order of 
screening date on the computer-generated document. One master list will be maintained in a confidential central 
shared folder for use.  Subjects will be replaced on an ongoing list if they drop out. 
 
Participants will be instructed to consume HAMS-AB with food, such as apple sauce or oatmeal, in two divided 
doses at breakfast and dinner at a total daily dose to be calculated as has been previously described for children: 
10g plus 1g per year of age daily [44]. The prebiotic will be dispensed by the Investigational Drug Services (IDS) 
at Indiana University. 
 
HAMS-AB will be in the form of acetylated and butyrylated HYLON® VII corn starch. 


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6.3 
SCHEDULE OF EVENTS 
 
Study Phase 
Screening 
Baseline- 
Intervention 
Washout 
Crossover- 
Intervention 
Follow-Up 
Early Termination 
Visit 
Visit Number 
1 
2 
3 
4 
5 
Visit Window 
< 30 days after 
Visit 1 
+/- 3 days 
28 days after 
Visit 2 
+/- 3 days 
28 days after 
Visit 3 
+/- 3 days 
28 days after 
Visit 4 
Informed consent/Assent 
X 
Inclusion/Exclusion criteria 
X 
Historical Data/Demographics* 
X 
Pancreatic Autoantibodies † 
X 
Random C-peptide concentration†† 
X 
Randomization 
X 
Pregnancy test** 
X 
X 
X 
X 
X 
X 
Current Medical data*** 
X 
X 
X 
X 
X 
Pubertal Tanner staging with physical exam 
X 
 
 
Ht/Wt measurement and vitals 
X 
X 
X 
X 
X 
X 
Supervised CGM insertion (and training, if 
applicable on use) ††† 
X 
X 
C-peptide by 2-hr MMTT†††† 
X 
X 
X 
HbA1c 
X 
X 
X 
Blood samples for biomarkers (PI:C and INS 
DNA) 
X 
X 
X 
X 
X 
Provision of HAMS-AB 
X 
X 
CGM download 
X 
X 
X 
Stool samples**** 
X 
X 
X 
X 
X 
Whole blood for additional T1D testing 
X 
X 
X 
X 
X 
Serum and plasma for storage^ 
X 
X 
X 
X 
X 
Adverse event assessment***** 
X 
X 
X 
X 
X 
Dietary Assessments******* 
X 
X 
X 
X 
X 
Verbal Diet recall 
X 
Sampling of prebiotic  
X 


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Data Collection: 
*Historical data: Date of birth, sex, Race/Ethnicity, date of diagnosis of T1D. 
**To be done in girls of reproductive potential. 
***Current Medical Data (All visits except screening): Medication use including types of insulin, means of insulin administration, and total daily insulin dose 
(u/kg body weight, averaged over the 3 days prior to each study visit), use of other medications. 
****Stool samples will be collected at home using a kit (Zymo feces catcher and RNA/DNA shield fecal collection tubes) within 3 days of presentation to each 
visit. 
*****Participants will be assessed for safety with questions regarding general well-being as well as specific questions to evaluate for adverse events. Participants will 
also be questioned about stool form and frequency, gastrointestinal symptoms, fevers, or infection. 
*******Dietary Assessments will be ideally obtained using the Automated Self-Administered 24-Hour (ASA24) dietary assessment tool [46-48], a web-based tool 
for administering automatically coded, self-administered recalls/food records. This will allow assessment of dietary fiber intake along with other dietary components. 
Participants will be asked to fill these in for the 24 hrs. diet recall prior to each stool collection in a time frame of +/- 3 days from the stool sample collection. This 
can also be completed during the study visit. Diet diaries will be accepted in lieu of the online questionnaire. Participants will be asked to record all meals and snacks, 
time of day, number of servings, major food components or description (for example chicken or protein), estimated portion sizes and whether they completed the 
meal or not, and any drinks including water. 
†Pancreatic autoantibodies to be tested only in those with no evidence of being tested for antibodies in their medical chart to confirm T1D. 
††Random, non-fasting c-peptide: C-peptide level will be analyzed at Indiana University Translation Core Lab using a two site immuno-enzymometeric assay using 
a Tosoh 2000 auto- analyzer (TOSOH, Biosciences, Inc., South San Francisco, CA). The C-peptide assay is calibrated against the WHO IS 84/510 standard and 
has a sensitivity level of 
0.05 ng/mL. 
†††At visit 2 (baseline/intervention) and 4 (crossover), a blinded CGM sensor will be inserted in those participants who are not currently using a CGM as part 
of their routine care. Training will be provided on calibration of the sensor, its use in blinded mode, and sensor insertion. Participants will be reminded to insert 
a sensor at home after approximately 14 days and continue using the blinded sensor for an additional 14 days. Participants will use their own home blood 
glucose meter or (if had been previously using one) CGM for regular blood glucose monitoring. The participant will return after 4 weeks to assess the CGM data. 
CGM must be used for at least 200 hours (equivalent to 8.3 days out of 14 days) 
††††C-peptide by 2-h MMTT: 2-hour MMTT will be performed using the standardized protocol utilized by the TrialNet Centers [51]. The early 
discontinuation MMTT will only be done if it has been at least 6 weeks since the last MMTT. 
^Serum and Plasma for storage – subject has option to consent or deny storage. Will be used for future type 1 diabetes research assays. 


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6.4 STUDY VISITS 
 
Visit 1 – Screening  
This visit will be at the hospital or research center. It will last approximately 1-2 hours and will include: 
• 
Obtain informed consent/assent documents and determine inclusion and exclusion criteria 
• 
Measurement of height and weight to determine BMI percentile eligibility and physical exam including 
pubertal staging 
• 
Obtaining Vital signs (heart rate, temperature, blood pressure, and respiratory rate) 
• 
Obtaining medical history 
• 
Dietary assessment by verbal recall 
• 
Obtaining blood sample (approximately 1.5 tablespoon) – Random non-fasting c-peptide, pancreatic 
autoantibodies if not previously done to confirm T1D diagnosis 
• 
For female adolescents: urine will be collected for a pregnancy test 
• 
Subject to sample prebiotic for palatability to ensure compliance  
Visit 2 – Baseline-Intervention 
This visit will be at the hospital or research center. It will last approximately 1-2 hours and will include: 
• 
Measurement of weight and bedside nurse assessment such as general appearance, respiratory and 
cardiac assessment. 
• 
Obtain vital signs (heart rate, temperature, blood pressure, and respiratory rate) 
• 
Collecting a diet history (diary or questionnaire) 
• 
Collecting Adverse Events (if applicable) 
• 
Obtaining medical history and insulin use 
Obtaining blood samples (approximately 2 tablespoons) – HbA1c, Serum biomarkers of beta cell stress 
and death (PI:C and INS DNA), other T1D testing, and serum and plasma for storage. 
o Some of the blood will be stored for future T1D research  use 
• 
CGM placement and training for participants not currently using one. 
• 
For female adolescents: urine will be collected for a pregnancy test 
• 
Collecting stool samples prior to or the morning of the visit (a stool collection kit will be shipped to the 
participants once eligibility is confirmed) 
• 
Study Randomization to either supplement or standard of care diabetes management and a diabetic diet. 
– Supplement (HAMS-AB) will be provided and will be taken by mouth twice daily with food such as apple 
sauce or oatmeal as described in Section 6.2. Instructions will be provided for recommendations on a 
healthy diabetic diet. 
• 
A new stool collection kit will be provided for the next visit 
 
Visit 3 - Washout 
This visit will be at the hospital or research center. It will last approximately 2-4 hours and will include: 
• Measurement of weight, assessment of CGM insertion sites, as well as bedside nurse assessment such as 
general appearance, respiratory and cardiac assessment. 
• 
Obtaining Vital signs (heart rate, temperature, blood pressure, and respiratory rate) 
• 
Collecting a diet history (diary or questionnaire) 
• 
Collecting Adverse Events (if applicable) 
• 
Obtaining medical history and insulin use 
• 
CGM download 
• 
For female adolescents: urine will be collected for a pregnancy test 
• 
Collecting stool samples prior to or the morning of the visit 
• 
Obtaining fasting blood sample (approximately 5 tablespoons) – Serum biomarkers of beta cell stress 
and death (PI:C and INS DNA), other T1D testing, and serum and plasma for storage and MMTT 


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samples (see below), and serum and plasma for storage 
o Some of the blood will be stored for future T1D research  use 
• 
Completion of a mixed meal tolerance test (MMTT).  See below. 
• 
After completion of this visit, participants will be instructed to follow a regular diet with no supplement 
intake for the following 4 weeks and to follow standard diabetes care as instructed by their diabetes 
provider. 
• 
A new stool collection kit will be provided for the next visit 
Preparing for an MMTT 
• 
Subjects will be asked to fast except for water for at least 10 hours prior to visit. 
• 
Subjects will be asked to limit strenuous activity for at least 10 hours prior to visit. 
• 
Subjects will be asked to consume at least 150 g of carbohydrates each day for 3 days. 
• 
If subject experiences hypoglycemia, morning of the visit, subjects will be instructed to treat low 
blood sugar and to reschedule MMTT procedure. 
 
MMTT Visit procedures 
Blood glucose will be tested and the MMTT started if blood glucose <200 by 10:00am. Long-acting 
insulin may be taken per routine, but short acting insulin must not have been given within 2 hours of 
MMTT. 
An IV catheter will be placed in the arm by trained nurses for blood drawing purposes. Blood will be drawn 10 
minutes prior to drinking Boost, just prior to drinking Boost, 15, 30-, 60-, 90-, and 120-minute post Boost 
consumption. High Protein Boost will be measured to a dose of 6ml/kg body weight (maximum dose 360ml). 
Total volume of blood will be approximately (5 tablespoons) not to exceed 5ml/kg/day. 
 
Visit 4 Crossover-Intervention 
This visit will be at the hospital or research center. It will last approximately 1-2 hours and will include: 
• Measurement of weight, assessment of CGM insertion sites, as well as bedside nurse assessment such as 
general appearance, respiratory and cardiac assessment. 
• 
Obtaining vital signs (heart rate, temperature, blood pressure, and respiratory rate) 
• 
Collecting a diet history (diary or questionnaire) 
• 
Collecting Adverse Events (if applicable) 
• 
Obtaining medical history and insulin use 
• 
Obtaining blood samples (approximately 2tablespoon) – Serum biomarkers of beta cell stress and 
death (PI:C and INS DNA), other T1D testing, and serum and plasma for storage 
o Some of the blood will be stored for future T1D research use 
• 
For female adolescents: urine will be collected for a pregnancy test 
• 
Supplement (HAMS-AB) will be provided and will be taken by mouth twice daily in the treatment arm 
as above in addition to insulin for diabetes management. Those in the control arm will follow standard 
diabetes management in addition to a recommended diabetic diet. 
• 
New CGM supplies given, if applicable. 
• 
Collecting stool samples 3 days prior to or the morning of the visit 
• 
A new stool collection kit will be provided for the next visit 
 
Visit 5 Follow-Up and/or Early Termination Visit 
This visit will be at the hospital or research center, will last approximately 2-4 hours and will include: 
• 
Measurement of height and weight and assessment of CGM insertion sites 
• 
Obtaining vital signs (heart rate, temperature, blood pressure, and respiratory rate) 
• 
Collecting a diet history (diary or questionnaire) 
• 
Collecting Adverse Events (if applicable) 


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• 
Obtaining medical history and insulin use 
• 
Obtaining blood samples (approximately 5 tablespoons) – HbA1c, Serum biomarkers of beta cell stress 
and death (PI:C and INS DNA), MMTT samples (see above), other T1D testing, and serum and 
plasma for storage 
o Some of the blood will be stored for future use 
• 
For female adolescents: urine will be collected for a pregnancy  test 
• 
Completion of a mixed meal tolerance test (MMTT) See Visit 3 for details. 
• 
CGM download 
• 
Collecting stool samples prior to or the morning of the visit 
An early discontinuation MMTT will only be done if it has been at least 6 weeks since the last MMTT. 
 
6.5 ONGOING DIABETES MANAGEMENT 
 
All study participants will have a treating endocrinologist who is primarily responsible for their diabetes care. In 
general, the expectation is that all participants will receive at least three injections of insulin daily, including 
short- and long-acting insulin preparations, or will utilize continuous subcutaneous insulin infusion (CSII, 
insulin pump). As part of diabetes monitoring during the subjects’ participation, we will encourage participants 
to check glucose levels at least four times daily if using blood glucose monitor and if not already using a CGM. 
At the time of visits the study team will suggest changes that they believe would improve the glucose control, 
if necessary. Letters summarizing the study visit will also be sent to the endocrinologist after parental agreement. 
 
In addition, insulin use, hypoglycemic events, and any episodes of ketoacidosis will be captured at each visit on 
the appropriate CRFs. 
 
Participants will be requested to record the amount of insulin they have used during the 3-day period 
immediately preceding each study visit. Insulin use logs will be provided to participants at each study visit and 
collected at the next visit. These logs will serve as the source documents. 
 
6.6 
BANKED SPECIMENS 
 
Serum and plasma will also be banked and stored at Indiana University for other type 1 diabetes related assays 
and for potential future use by other investigators. Participants will have the option to not have samples stored 
on the informed consent documents. 
 
7.0    REPORTING OF ADVERSE EVENTS OR UNANTICIPATED     
PROBLEMS INVOLVING RISK TO PARTICIPANTS OR OTHERS 
7.1 
UNANTICIPATED PROBLEMS 
 
In the unlikely event of an acute emergency with a subject, all procedures will be performed in a hospital setting 
by trained personnel. 
 
In the event of physical injury resulting from the participation in this research, necessary medical treatment will 
be provided and billed as part of their medical expenses. Costs not covered by health care insurer will be the 
subject’s responsibility. Also, it is the subject’s responsibility to determine the extent of health care coverage. 
There is no program in place for other monetary compensation for such injuries. However, the subject will not 
give up any legal rights or benefits to which he/she is otherwise entitled. If any severe adverse events occur 
while not at a medical facility, the subject will be responsible for seeking medical care and for the expenses 
associated with any care received. 


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7.2 
DATA SAFETY MONITORING 
 
The data safety monitoring plan involves Dr. Zeina Nabhan, MD, a pediatric endocrinologist, to review 
this study for data for quality, rate of subject recruitment, adverse events, procedures for protecting patient 
privacy, and any protocol deviations every 6 months following the first subject enrolled. If the review 
concludes that there are significant safety concerns or quality of the data is unsatisfactory, no further 
enrollment will occur until these issues have been addressed and any changes to the study approved by the 
IUPUI IRB. 
7.3 
ADVERSE EVENTS 
 
An adverse event is defined as any unintended or abnormal clinical observation that is not of benefit to the 
patient. Either the condition was not present prior to exposure to study supplement, or it has worsened in 
intensity or frequency following exposure to the study supplement. Adverse events will be graded according to 
the National Cancer Institute (NCI) Common Terminology Criteria v5.0. 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_ 
5x7.pdf 
Any suspected or confirmed toxicity should be reported immediately (within 24 hours) to the principal 
investigator. 
 
Hypoglycemic and hyperglycemic events that are seen as part of daily diabetes management will not be 
considered adverse events unless they result in hospitalization 
 
Principal investigators (PI) will report to the IRB as soon as possible, but in all cases within 5 working days 
from notification any event that appears on the List of Events that Require Prompt Reporting to the IUPUI 
IRB. 
 
List of Events that Require Prompt Reporting to the IUPUI IRB: Any of the following: 
• 
Event (including adverse events, injuries, side effects during the research study), which in the 
opinion of the PI 
• 
caused harm to one or more subjects or others, or placed one or more subjects 
or others at increased risk of harm; AND 
• 
was unexpected; AND 
• 
was related to the research procedures 
 
Note: After the study is closed with the IRB, these events will only be reported if they are profound, or they 
demonstrate long-term risks that would necessitate notifying subjects. 
• 
Protocol deviation/violation (as defined under this policy) 
• 
Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to a 
research subject (e.g., purposeful and for subject safety) 
• 
Complaint of a subject that indicates unexpected risks, or complaint that cannot be resolved by the 
research team 
• 
Interim findings and safety monitoring reports that indicate an unexpected change to the risks or 
potential benefits of the research, in terms of severity or frequency 
• 
Publication in the literature that indicates an unexpected change to the risks or potential benefits of 
the research 
• 
Change in FDA labeling or withdrawal from marketing of the supplement used in this research 
study 
• 
Noncompliance (as defined in this policy) 


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8.0    STATISTICAL CONSIDERATIONS 
A sample size of 12 with a cross over design (i.e., 12 per arm) is considered adequate to estimate effect sizes for 
efficacy to aid in designing future trials for responses that are normally distributed [52]. Simple comparisons will 
be performed using chi-square for categorical variables and t-tests for continuous variables. Random attritions 
and failed screens will be replaced. An intention to treat analysis will not be appropriate given the crossover design. 
Adverse events will be presented as the proportion of each event seen. This is considered a minimal risk study 
with low risk for minor adverse events such as mild gastrointestinal symptoms that could be related to increased 
dietary fiber intake. Our primary outcome is changes in the gut microbiome profile. To determine the diversity 
and richness of the microbiome, we will calculate a diversity index for both the pre- and post-intervention time 
points for each recipient. Microbial sequence analysis and statistics will be analyzed using the Quantitative Insights 
into Microbial Ecology (QIIME) 1.8.0 software as previously described [53]. 
 
8.0    PRIVACY/CONFIDENTIALITY ISSUES 
 
Data sources will include paper and electronic medical records and test results. Data will be recorded on paper, 
desktop computers, and laptop computers. The Principal Investigator, Research Coordinators, Co- 
Investigators, Biostatistics, and Governmental Agencies will have access to the individually identifiable data. 
This data will be safeguarded by locking storage cabinets and office doors, keeping information in areas with 
limited public access, password protecting computers and files, and regular back-ups of electronic data. Data 
will be retained indefinitely. When confidential data need to be discarded, paper records will be shredded, 
CD’s and diskettes will be destroyed, and data will be permanently deleted from computers. When possible, 
only de-identified data will be shared. If identifiable data will be shared, it will be done by fax in a secured 
area, on a shared drive with password protection, or by personal delivery by authorized research personnel. 
 
10.0   FOLLOW-UP AND RECORD RETENTION 
10.1 
RECORD RETENTION 
The duration of this study is expected to be 2 years. All specimens and records will be held as required by 
law and until no further questions arise from the data. 
 
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signature of obesity in a large study of American adults. Sci Rep. 2018 Jun 27;8(1):9749. doi: 10.1038/s41598-018-28126- 
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Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, Goland RS, Greenberg EM, Liljenquist DR, 
Ahmann AJ, Marcovina SM, Peters AL, Beck RW, Greenbaum CJ; T1D Exchange Clinic Network. Prevalence of 
detectable C-Peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 2015 Mar;38(3):476- 
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Rose DJ, Patterson JA, Hamaker BR: Structural differences among alkali‐soluble arabinoxylans from maize (Zeamays), 
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Bergenstal RM, Gal RL, Connor CG, Gubitosi-Klug R, Kruger D, Olson B, Willi S, Aleppo G, Weinstock RS, Wood J, 
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Baghurst PA. Calculating the mean amplitude of glycemic excursion from continuous glucose monitoring data. Diabetes 
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Watkins RA, Evans-Molina C, Terrell JK, Day KH, Guindon L, Restrepo IA, Mirmira RG, Blum JS, DiMeglio LA. 
Proinsulin and heat shock protein 90 as biomarkers of beta-cell stress in the early period after onset of type 1 diabetes. 
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Fisher MM, Watkins RA, Blum J, Evans-Molina C, Chalasani N, DiMeglio LA, Mather KJ, Tersey SA, Mirmira RG. 
Elevations in circulation methylated and unmethylated preproinsulin DNA in new-onset type 1 diabetes. Diabetes. 2015 
Nov;64(11):3867-72. doi: 10.2337/db15-0430. Epub 2015 Jul 27. PMID: 26216854 
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Greenbaum CJ, Beam CA, Boulware D et al. Fall in C-peptide during first 2 years from diagnosis: evidence of at least 
two distinct phases from composite Type 1 Diabetes TrialNet data. Diabetes 2012;61(8):2066-2073. 
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Aryana K, Greenway F, Dhurandhar N, Tulley R, Finley J, Keenan M, Martin R, Pelkman C, Olson D, Zheng J. A 
resistant-starch enriched yogurt: fermentability, sensory characteristics, and a pilot study in children. F1000Res. 2015 
Jun 1;4:139. doi: 10.12688/f1000research.6451.1. eCollection 2015. PMID: 26925221 
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Diabetes Care Jan 2018, 41 (Supplement 1) S13-S27; DOI: 10.2337/dc18-S002 
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National Cancer Institute. Automated self-Administered 24-hour recall (ASA24) Dietary Assessment Tool National 
Cancer Institute; 2018 (https://epi.grants.cancer.gov/asa24/). Last accessed January 7th, 2019. 
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Blanton CA, Moshfegh AJ, Baer DJ, Kretsch MJ. The USDA Automated Multiple-Pass Method accurately estimates 
group total energy and nutrient intake. The Journal of nutrition. 2006;136(10):2594-9. 
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Moshfegh AJ, Rhodes DG, Baer DJ, Murayi T, Clemens JC, Rumpler WV, et al. The US Department of Agriculture 
Automated Multiple-Pass Method reduces bias in the collection of energy intakes. The American journal of clinical 
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meals/create-your-plate/#seven last accessed 03/15/2019. 
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Smart CE, Annan F, Higgins LA, Jelleryd E, Lopez M, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: 
Nutritional management in children and adolescents with diabetes. Pediatr Diabetes. 2018 Oct; 19 Suppl 27:136-154. 
doi: 10.1111/pedi.12738. DOI: 10.1111/pedi.12738 PMID: 30062718 
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Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Burkhard Haastert, Ludvigsson J, Pozzilli P, Lachin JM, 
Kolb H. Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in 
Therapeutic Trials in Type 1 Diabetes. Diabetes Care Oct 2008, 31 (10) 1966-1971; DOI: 10.2337/dc07-2451 
52 
Julious S. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical Statistics 2005;4(4):287-291 
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Sanchez-Alcoholado L, Castellano-Castillo D, Jordan-Martınez L, et al. Role of gut microbiota on cardio-metabolic 
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2017; 8: 1936. 

ICF_001.pdf: 
 
 
 
 
Title: Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell Function in 
Newly Diagnosed Type 1 Diabetes  
 
NCT: 04114357 
 
Date of IRB Submission:  August 25, 2022   
 
 
 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
2 
 
 
INDIANA UNIVERSITY INFORMED CONSENT STATEMENT FOR 
 
Evaluating the Effect of Prebiotics on the Gut Microbiome Profile and β-cell Function in 
Newly Diagnosed Type 1 Diabetes 
 
Your child is invited to participate in a research study using a prebiotic to see its effects on insulin production and 
gut bacteria in persons with newly diagnosed with type 1 diabetes.  A prebiotic is a special form of dietary fiber that 
we think will help control your diabetes and help feed the good bacteria found in the gut.  Your child was selected 
to participate because he/she was diagnosed with type 1 diabetes in the past 3 years and is between the ages of 11 
and 17 years old. We ask that you read this form and ask any questions you may have before agreeing to your child 
being in the study.  “You” may refer to you or your child throughout this document. 
 
The study is being conducted by Dr. Heba Ismail at Indiana University in the Division of Pediatric Endocrinology.  
It is funded by the Department of Pediatrics at Indiana University. 
 
STUDY PURPOSE 
 
The purpose of this study is to determine if using a prebiotic has an effect on blood sugars and the amount of stress 
that is experienced by the body’s cells that make insulin. These cells are called beta cells.  This prebiotic also has an 
effect on restoring the balance and composition of bacteria normally living in the intestine.  We hope to be able to 
learn more about whether this prebiotic may be a useful supplement for persons with type 1 diabetes. The prebiotic 
being studied is not FDA approved, so this is considered “investigational.” 
 
NUMBER OF PEOPLE TAKING PART IN THE STUDY: 
 
If your child agrees to participate, he/she will be one of up to 24 participants. This study will last about 12 weeks 
and involves 5 visits.  Each participant will take a prebiotic for 4 weeks along with following the usual diabetic diet 
recommendations, followed by a 4-week break and then 4 more weeks following the usual diabetic diet 
recommendation only or vice versa. The prebiotic used is called HAMS-AB.   
 
Everyone is expected to follow the recommended diet during the study, except during the 4-week break. Some 
children will start with the prebiotic and end with the diet recommendations while others will start with the diet 
recommendations and end with the prebiotic.  
 
The process of figuring out which your child will start with is called randomization and is determined by chance 
(like flipping a coin).  
 
PROCEDURES FOR THE STUDY: 
 
If you agree to be in the study, your child will do the following things: 
 
For visits 2, 3 and 5, your child will need to fast.  This means he/she cannot eat or drink anything except for water 
for ten hours prior to the study visit.  These fasting visits will need to be scheduled in the morning. We will also 
measure height, weight, blood pressure, heart rate, and temperature at each visit. We will examine your child as 
well as check his/her insulin use. At each visit except Visit 1, we will ask your child to collect a stool sample 1-3 
days before each visit. We will provide you with stool sample collection kits and instructions.  
 
Visit 1 (Screen): This visit may take up to 2 hours.  
 
Before the study starts, we will talk to you about the study and answer any questions you have. You will be asked 
to sign this consent form, give your child’s health history, medicines he or she takes, and other information needed 
to determine if your child is eligible. This visit will also include: 
 
• 
Physical examination by the study doctor. 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
3 
 
• 
Take a blood sample (approximately 1.5 tablespoons) to measure whether your body continues to make 
some of its own insulin and other markers related to diabetes. 
• 
For female adolescents: urine will be collected for a pregnancy test  
o We will ask you to have a pregnancy test before you start this study. Parents of participants who 
are less than 14 years old, will be told the result of the pregnancy test.  Participants who are 14 
years old or older, will only themselves be told the results, but will also be advised on how to get 
care for the pregnancy including the support of an adult.  
o You will not continue in the study if your pregnancy test is positive. 
o If there is any chance that your child is pregnant or might become pregnant during the time of this 
study, we would recommend that you think carefully about whether she should participate.  
• 
We will notify you of your child’s lab results. 
• 
We will ask about your child’s diet to determine if they can participate in the study. 
• 
We will ask your child to try the prebiotic with applesauce or oatmeal to make sure your child will be able 
to eat the study prebiotic without any problems. 
• 
If we find that your child is continuing to make some of his/her own insulin and meet certain height and 
weight measurements, he/she will be invited back for the next step. We will provide you with a stool 
collection kit for the next visit. You will also be provided information on how to fill a diet recall form for 
the 24 hours prior to the stool sample collected.  
 
Visit 2 (Treatment Start): This visit may take 1-2 hours 
 
This visit will include: 
 
• 
Asking you about changes in your child’s medical history since the last visit, including insulin use.  
• 
A brief physical assessment by the bedside nurse. 
• 
You will also be asked to fill out a diet history questionnaire or provide a diet diary (this can be done prior 
to the visit). 
• 
For female adolescents: urine will be collected for a pregnancy test  
• 
Taking a blood sample (approximately 2 tablespoons) to measure your blood sugar control and other things 
about your diabetes. 
o Some of the blood taken from you will be saved for the study doctors to use later.  This is optional 
and you will be asked whether you agree to this at the end of this document. 
• 
We will obtain from you the stool sample collected prior to or the same day as the visit.  
• 
You will be provided with a new stool collection kit for the next visit and logs for logging insulin doses. 
• 
If you are not currently using one, we will then place a continuous glucose monitor (CGM), sometimes also 
referred to as sensor. You will be asked to wear this for 4 weeks. This CGM will need to be changed after 
14 days or if it falls out. You and your child will be trained on how to insert a new CGM. You will be 
provided with two additional CGMs for this purpose. If using the CGM provided through the study, you 
will not be able to see the sugar values on this monitor as they are collected but the investigators will be 
able to access these data when you return the device and they will help the investigator understand if your 
sugars are affected by taking the treatment.  
• 
A computer program will randomize your child to either taking the prebiotic first twice a day for 4 weeks 
or not. You will be given a supply to last the 4 weeks and you will be asked to mix it with food such as 
applesauce or oatmeal. Whether you are randomized to start with the prebiotic or not, current diet 
guidelines for people with diabetes will be given to you to follow for those 4 weeks. 
 
Visit 3 (After Treatment – 4 weeks after enrollment):  This visit may take 2-4 hours 
 
• 
We will ask you questions about your medical history, including your insulin use and any problems you are 
having with the medications. 
• 
A brief physical assessment by the bedside nurse. 
• 
We will download the glucose data from the CGM. 
• 
For female adolescents: urine will be collected for a pregnancy test  
• 
You will also be asked to fill out a diet history questionnaire or provide a diet diary (this can be done prior 
to the visit). 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
4 
 
• 
Take blood samples (approximately 5 tablespoons total including for the mixed meal tolerance test below) 
to measure your blood sugar control and other things about your diabetes 
o Some of the blood taken from you will be saved for the study doctors to use later.  This is 
optional and you will be asked whether you agree to this at the end of this document. 
• 
Your child will complete a mixed meal tolerance test (MMTT) which involves drinking Boost®. It is like a 
milkshake, and it will raise his/her blood sugar. The study doctors use this test to determine how much 
insulin your child’s beta cells can make. You will be given specific instructions on insulin dosing and diet 
for 3 days prior to the MMTT. On the morning of the test, your child may only drink water and will not 
take short-acting insulin within 2 hours of the test. Your child will also be asked to not exercise 10 hours 
prior to this test as this can alter his/her blood sugar level. An IV cannula (plastic tube in vein) will be 
placed in his/her arm for drawing blood. Blood will be drawn from the IV cannula before drinking the 
Boost®. Your child will be given 5 minutes to drink the Boost®, and then blood will be drawn up to 7 times 
for 2 hours.  The amount of the drink will depend on your child’s body weight but will be no more than 12 
ounces.  
• 
We will obtain from you the stool sample, your child collected prior to this visit.  You will be provided 
with a new stool collection kit for your next visit as well as insulin dose log sheets. 
• 
You can then take a break from following the recommended diet for the next 4 weeks. If you were taking 
the supplement in addition, you will stop taking it for the next 4 weeks. 
 
Visit 4 (Cross-over – 8 weeks after enrollment):  This visit may take 1-2 hours 
 
This visit includes: 
• 
We will ask you questions about your medical history, including your insulin use and any problems you are 
having with the medications.  
• 
A brief physical assessment by the bedside nurse. 
• 
For female adolescents: urine will be collected for a pregnancy test  
• 
You will also be asked to fill out a diet history questionnaire or provide a diet diary (this can be done prior 
to the visit). 
• 
Take blood samples (approximately 2 tablespoons) to measure your blood sugar control and other things 
about your diabetes. 
o Some of the blood taken from you will be saved for the study doctors to use later.  This is optional 
and you will be asked whether you agree to this at the end of this document. 
• 
We will obtain from you the stool samples your child collected.  
• 
We will provide you with a new stool collection kit for your next visit as well as insulin dose log sheets. 
• 
You will need to restart following the recommended diet. If it is your turn to now start using the 
supplement, then you will be given a supplement supply at this visit to be taken twice daily for 4 weeks and 
to be mixed each time with food such as applesauce or oatmeal. 
• 
You will be asked to insert a new CGM at this visit if using the CGM provided through the study. You will 
need to change the CGM after 14 days, or if it falls out. We will provide you with 2 additional CGMs. 
 
Visit 5 (Post Study Follow-Up) This visit  may take 2-4 hours. 
 
This visit includes:  
• 
Physical examination by the study doctor. 
• 
We will ask you questions about your medical history, including your insulin use, and problems taking you 
are having with the medications.  
• 
For female adolescents: urine will be collected for a pregnancy test. 
• 
You will also be asked to fill out a diet history questionnaire or provide a diet diary (this can be done prior 
to the visit). 
• 
Take blood samples (approximately 5 tablespoons total including for the mixed meal tolerance test below) 
to measure your blood sugar control and other things about your diabetes 
o Some of the blood taken from you will be saved for the study doctors to use later.  This is 
optional and you will be asked whether you agree to this at the end of this document. 
• 
Your child will complete a mixed meal tolerance test (MMTT) which involves drinking Boost®. It is like a 
milkshake, and it will raise his/her blood sugar. The study doctors use this test to determine how much 
insulin your child’s beta cells can make. You will be given specific instructions on insulin dosing and diet 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
5 
 
for 3 days prior to the MMTT. On the morning of the test, your child may only drink water and will not 
take short acting insulin within 2 hours of the test. Your child will also be asked to not exercise 10 hours 
prior to this test as this can alter his/her blood sugar level. An IV cannula (plastic tube in vein) will be 
placed in his/her arm for drawing blood. Blood will be drawn from the IV cannula before drinking the 
Boost®. During the MMTT, no more than 5 tablespoons of blood will be drawn. Your child will be given 5 
minutes to drink the Boost®, and then blood will be drawn up to 7 times for 2 hours.  The amount of the 
drink will depend on your child’s body weight but will be no more than 12 ounces.  
• 
We will obtain from you the stool samples your child collected.  
• 
We will download your CGM at this visit. 
Early Discontinuation Visit: 
Treatment will stop and we will ask that you will return for an exit visit if any of the following conditions occur: 
• withdrawal of consent (we ask that you return for this exit visit, but you are not required to return) 
• pregnancy (female participants) 
• any medically important event such as a concurrent severe illness or complications 
•  it is in your best interest to stop the study in the investigator’s judgment 
You will have a visit at the hospital or research center, and it will last approximately 2-3 hours and will include: 
• 
Measure your height and weight, check your vital signs, and examine you. 
• 
We will ask you questions about your medical history, including your insulin use. 
• 
Physical examination by the study doctor. 
• 
For female adolescents: urine will be collected for a pregnancy test  
• 
You will also be asked to fill out a diet history questionnaire or provide a diet diary (this can be done prior 
to the visit). 
• 
You will be asked to provide a stool sample from the previous 3 days collected using the collection kit we 
provided you. 
• 
Take blood samples (approximately 5 tablespoons total) to measure your blood sugar control and other 
things about your diabetes. This will include a MMTT if it has been 6 weeks since the last MMTT. 
 
Some of the blood taken from you will be saved for the study doctors to use later.  This is 
optional and you will be asked whether you agree to this at the end of this document. 
 
RISKS OF TAKING PART IN THE STUDY: 
 
While in the study, there may be side effects, risks, or discomforts.  The most common and likely risks are 
described below; however, there may be some risks that are unknown. You/your child should discuss these with the 
study doctor. There is always the possibility that unknown or unexpected injuries might happen.  There is a chance 
that your diabetes control may improve or worsen while you are involved in this study. 
 
a. Blood Drawing and Urine Collection: 
You/your child may have discomfort and/or a bruise when you get your blood drawn. Occasionally, some 
people may faint. It is rare, but some people may get an infection, a small blood clot, swelling of the vein 
and surrounding tissue, or bleeding at the needle puncture site. We will have trained medical professionals 
drawing blood to decrease these risks.  
 
b. MMTT: 
There are some risks with the MMTT. Use of Boost® during this test has no known side effects, but you/your 
child may not like the taste. Some people are allergic to soy or dairy products found in Boost®. If your child 
has any of these allergies, he/she will not be asked to participate. A hollow needle/plastic tube will be placed 
in your arm for taking blood samples during the MMTT.  When the needle goes into a vein, it hurts for a 
short time.  A special numbing cream may be used to make it hurt less.  The most common risks related to 
putting the numbing cream (LMX or EMLA) on the skin are redness, blanching (temporary whiteness of the 
skin area), swelling, and itching.  There may be minor discomfort from having the needle/plastic tube taped 
to your arm. There is a small risk of bleeding under the skin that will produce a bruise. There is a small risk 
of a blood clot forming in the vein, infection, or significant blood loss. We will have trained medical 
professionals inserting the IV to decrease these risks.   
 


 
 
 
 
 
 
 
 
 
 
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Ver 11.0 – August 2022 
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c. Risks of using the supplement: 
The risks of this study include possible side effects of using the prebiotic supplement.  Known risks of 
using the prebiotic supplement are derived from prior studies of the supplement in adults and children.  
Some of these are likely related to the intake of a relatively larger amount of fiber than typically consumed.   
 
Likely: initial abdominal discomfort and increase in frequency of bowel movements 
 
d. Potential risk for pregnancy: There is no evidence suggesting toxicity to fetuses with the supplement or 
placebo.  Males participating in the study do not need to use contraceptive methods. Although generally 
considered to be safe, it has not been specifically studied in pregnant women and therefore, females of 
childbearing age will be asked to use the following: 
 
Effective Forms of Birth Control – any one of the following (additionally, participants will be counselled on 
the use of a second method of contraception): 
 Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate <1%), for 
example hormone vaginal ring or transdermal hormone contraception 
 Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
 Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository 
 
e. Risks related to CGM/sensor use: 
The sensor may produce pain when it is inserted into the skin. There is a low risk for developing a local 
skin infection at the site of the sensor needle placement.  Itchiness, redness, bleeding, and bruising at the 
insertion site may occur as well as local tape allergies.   
 
f. Loss of Confidentiality: 
There is the unlikely chance that health information is viewed by someone outside the research team who is 
not authorized to see health information.  Efforts will be made to keep all personal information 
confidential. All data will be de-identified and stored with numerical identification and files will be kept in 
locked cabinets within locked rooms. Electronic data will be protected by 2 password systems 
(computer/database).  
 
You may not experience any of these risks or you might have a problem we cannot predict. If we become aware of 
any new risks, you will be told about them, and can decide if you want your child to continue to participate in the 
study.  
 
BENEFITS OF TAKING PART IN THE STUDY: 
 
While receiving HAMS-AB, there are potential benefits in reduction of beta cell stress. We also hope to learn more 
about type 1 diabetes and whether the use of this supplement might improve glucose levels and/or improve beta cell 
health in general as well as restore the gut bacterial balance. 
 
ALTERNATIVES TO TAKING PART IN THE STUDY: 
 
Instead of being in this study, you can decide not to participate and receive standard treatment for your type 1 
diabetes. This will not affect your medical care.  
 
WILL I RECEIVE MY RESULTS? 
 
We may learn things about you from the study activities which could be important to your health or to your 
treatment.  If this happens, this information will be provided to you at the end of the entire study when all 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
7 
 
participants are done.  You may need to meet with professionals with expertise to help you learn more about your 
research results.  The study team/study will not cover the costs of any follow-up consultations or actions. 
 
CONFIDENTIALITY 
 
Efforts will be made to keep your personal information confidential.  We cannot guarantee absolute confidentiality.  
Your personal information may be disclosed if required by law.  Your identity will be held in confidence in reports 
in which the study may be published. 
 
Organizations that may inspect and/or copy your research records for quality assurance and data analysis include 
groups such as the study investigator and his/her research associates, the Indiana University Institutional Review 
Board or its designees, the study sponsor (Indiana University School of Medicine) the Data Safety Monitoring 
Board, the Indiana Clinical Research Center, and (as allowed by law) state or federal agencies, specifically the 
Food and Drug Administration (FDA) and the National Institutes of Health (NIH), etc., who may need to access 
your medical and/or research records. 
 
During your child’s visits, as discussed above, blood samples will be collected.  The blood and stool samples will 
be sent to a laboratory to be tested along with the blood and stool samples from all other patients in the study.  The 
blood and stool samples will only be identified by the code number assigned to you/your child for the study. 
 
Results of the study will be reported in medical journals and may be presented at scientific meetings. However, at 
no time will any of the participants in the study be identified. Confidentiality of your/your child’s records will be 
maintained, and all records will be kept in accordance with current legal requirements.  
 
A description of this clinical trial will be available on ClinicalTrials.gov, as required by U.S. Law. This Web site 
will not include information that can identify you. At most, the Web site will include a summary of the results. You 
can search this Web site at any time.  
 
For the protection of your privacy, this research is covered by a Certificate of Confidentiality from the National 
Institutes of Health.  The researchers may not disclose or use any information, documents, or specimens that could 
identify you in any civil, criminal, administrative, legislative, or other legal proceeding, unless you consent to it.  
Information, documents, or specimens protected by this Certificate may be disclosed to someone who is not 
connected with the research: 
(1) if there is a federal, state, or local law that requires disclosure (such as to report child abuse or 
communicable diseases).  
(2) if you consent to the disclosure, including for your medical treatment.  
(3) if it is used for other scientific research in a way that is allowed by the federal regulations that protect 
research subjects. 
(4) for the purpose of auditing or program evaluation by the government or funding agency. 
(5)  if required by the federal Food and Drug Administration (FDA).    
 
A Certificate of Confidentiality does not prevent you from voluntarily releasing information about yourself.  If you 
want your research information released to an insurer, medical care provider, or any other person not connected 
with the research, you must provide consent to allow the researchers to release it. 
 
USE OF INFORMATION FOR RESEARCH IN THE FUTURE 
 
Information collected from you for this study may be used for future research studies or shared with other 
researchers for future research.  If this happens, information which could identify you will be removed before any 
information is shared.  Since identifying information will be removed, we will not ask for your additional consent. 
 
COSTS 
 
There is no cost to you for taking part in this study.  
 
 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
8 
 
 
 
PAYMENT 
 
Your child will receive payment for taking part in this study.  Your child will get $50 in the form of a payment card 
for each completed visit, up to a maximum of $250 if you complete the entire study.  In addition, parking will be 
paid for at each study visit. You will be reimbursed for mileage if your round trip is at least 30 miles roundtrip 
to the clinic at a rate of $0.17/mile. 
 
COMPENSATION FOR INJURY 
 
In the event of physical injury resulting from your participation in this research, necessary medical treatment will 
be provided to you and billed as part of your medical expenses.  Costs not covered by your health care insurer will 
be your responsibility.  Also, it is your responsibility to determine the extent of your health care coverage.  There is 
no program in place for other monetary compensation for such injuries.  However, you are not giving up any legal 
rights or benefits to which you are otherwise entitled.   
 
CONTACTS FOR QUESTIONS OR PROBLEMS 
 
For questions about the study or a research-related injury, contact the researcher Dr. Heba Ismail at 317-278-7041.  
If you cannot reach the researcher during regular business hours from 8:00 AM-5:00 PM, please call 317-944-3889. 
 
In the event of an emergency, you may contact Dr. Ismail at 317-274-5000 and ask for her to be paged or the 
pediatric endocrinologist on call. 
 
For questions about your rights as a research participant or to discuss problems, complaints, or concerns about a 
research study, or to obtain information, or offer input, contact the IU Human Subjects Office at (800) 696-2949 or 
irb@iu.edu. 
 
VOLUNTARY NATURE OF STUDY 
 
Taking part in this study is voluntary.  You may choose not to take part or may leave the study at any time.  
Leaving the study will not result in any penalty or loss of benefits to which you are entitled.  Your decision whether 
or not to participate in this study will not affect your current or future relations with Indiana University, Riley 
Hospital, or Pediatric Endocrinology.   
Your participation may also be stopped by the study doctor for any reason without your consent. This may happen 
if you start taking an antibiotic or another medication that can affect your blood sugar or the balance and 
composition of the bacteria living in the intestine. If this were to happen, the study doctor may allow you to resume 
study participation once you are no longer taking the medication 
 
STORED SAMPLES AND INFORMATION 
 
If you agree, we will store your remaining samples and additional storage of serum and plasma at Indiana 
University.  The purpose is to make these samples and information available for future research in diabetes or auto-
immune disorders which is not yet planned. New scientific discoveries may lead to new tests.  The tests may help 
researchers learn more about diabetes. These tests may include genetic testing. Genetic tests study an individual’s 
inherited characteristics, found in DNA, which is present in each of the cells in your body.  These tests may include 
whole genome sequencing, which involves mapping all your DNA. 
 
This research follows the Genetic Information Nondiscrimination Act (GINA), a federal law which generally makes 
it illegal for health insurance companies, group health plans, and most employers to request the genetic information 
we get from this research and discriminate against you based on your genetic information.   
Samples collected from you for this research may be used to develop products which could be sold in the future.  
The investigator does not plan to share any profits or losses from the sale of those products with you.   
 


 
 
 
 
 
 
 
 
 
 
IRB Study # 1907172784 
 
Ver 11.0 – August 2022 
9 
 
Your decision to allow samples and data to be stored is separate from your decision to participate in this study.  If 
you decide to allow storage, your samples and data may be stored for an unknown length of time.  No additional 
samples for storage are taken.  Remaining samples are stored when all other study required tests are completed.    
   
The results of tests done on your stored samples will not be given to you or your doctor.  The results will not be put 
in your records and will not change your medical care. There will be no benefits to you from the storage of these 
samples and information.  However, the use of your samples and information may help researchers learn more about 
diabetes or help study the genetics related to diabetes.   
 
You can change your mind at any time during the study and ask to have your samples destroyed.  This request should 
be made in writing to the study doctor or by phone to the study team.  If your samples have not been used, they will 
be destroyed.  If your samples have already been tested before your request, the information from these tests will be 
used and cannot be destroyed. 
 
Choose yes or no to allow the storage of your remaining samples (blood and stool) and information for future tests.   
 
Yes _______ (initials)  
 
 
No _______ (initials) 
 
 
 
SUBJECT’S CONSENT 
 
In consideration of all of the above, I give my consent for my child to participate in this research study.   
I will be given a copy of this informed consent document to keep for my records.  I agree to take part in this study. 
 
 
Subject’s Printed Name: ________________________________ 
 
 
 
Parent or Legal Guardian Printed Name: _________________________ 
 
 
 
Parent or Legal Guardian Signature: _______________________________    Date:  _______________ 
 
 
 
Printed Name of Person Obtaining Consent: _____________________________________ 
 
 
 
Signature of Person Obtaining Consent: __________________________        Date: _________________