Fiber Supplementation In Children With Peanut Allergy On Oral Immunotherapy: A Randomized Controlled Pilot Study
Phase: PHASE1
Conditions: Peanut Allergy
Sponsor: University of Chicago

 
RPS in POIT_v8 (17-AUG-2023) 
CLINICAL RESEARCH PROTOCOL 
 
 
 
 
 
 
 
 
FIBER SUPPLEMENTATION IN CHILDREN WITH PEANUT 
ALLERGY ON ORAL IMMUNOTHERAPY:  A RANDOMIZED 
CONTROLLED PILOT STUDY 
 
 
 
 
 
Principal Investigator: 
Christina E. Ciaccio MD MSc 
Department of Pediatrics 
5841 S. Maryland Ave; MC 5042 
Chicago, IL 60637 
773-834-4010 
Funding: 
DFI Multidisciplinary Grant 
Study Product: 
Fiber supplement (Resistant Potato Starch)  
(GRAS) 
Protocol Number: 
IRB21-0589 
IND Number: 
N/A 
 
 
 
 
 
 
 
 
 
 
 
Initial version: March 8, 2021 
Amended: 
August 30, 2021 
Amended: 
September 18, 2021 
Amended: 
October 6, 2021 
Amended: 
October 11, 2021 
Amended: 
October 19, 2021 
Amended: 
June 21, 2022 
Amended:          May 16, 2023 
Amended:          August 17, 2023  

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List of Abbreviations 
 
 
ACT 
 
 
 
asthma control test 
AE 
 
 
 
adverse event 
CBC 
 
 
 
complete blood count 
CRF 
 
 
 
case report forms 
DBPCFC 
 
 
double blind placebo controlled food challenge 
FS 
 
 
 
fiber supplement 
GALT  
 
 
gut associated lymphoid tissue 
GI 
 
 
 
gastrointestinal 
GRAS  
 
 
generally regarded as safe 
OIT 
 
 
 
oral immunotherapy 
PI 
 
 
 
principal investigator 
POIT  
 
 
peanut oral immunotherapy 
RPS 
 
 
 
resistant potato starch 
RMS  
 
 
resistant maize starch 
ACS 
 
 
 
accessible corn starch 
SAE 
 
 
 
serious adverse event 
SCFA  
 
 
short chain fatty acids 
UChicago  
 
 
The University of Chicago 

RPS in POIT 
 
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RPS in POIT_v8 (17-AUG-2023) 
Study Summary 
Title 
Fiber Supplementation in Children with Peanut Allergy on Oral 
Immunotherapy: A Randomized Controlled Pilot Study. 
Short Title 
Pinpoint Study 
Protocol Number 
UCM001 
Methodology 
Double Blind, Placebo Controlled Pilot Study 
Study Duration 
July 2021-June 2026 (estimated) 
Study Center(s) 
UChicago Medicine Comer Children’s Hospital 
UChicago Medicine Comer Children’s Merrillville 
UChicago Medicine South Loop 
Primary Endpoints 
• 
To determine the proportion of subjects who tolerate at least 
1043 mg cumulative of peanut protein with no more than mild 
symptoms at the 12-month DBPCFC 
Secondary 
Endpoints 
• 
To determine the proportion of subjects who experience dose 
related GI side effects during oral immunotherapy 
• 
To determine the proportion of subjects who experience 
hypersensitivity reactions (other than GI) during oral 
immunotherapy 
Exploratory 
Endpoints 
• 
To demonstrate the effect of resistant potato starch (RPS) on 
the fecal microbiome and metabolome 
• 
To determine if gnotobiotic mice colonized with the fecal 
microbiota of study participants models clinical response 
• 
To evaluate the immunological effects of fiber supplementation 
in children 
o Change in peanut specific IgE and IgG4 levels 
o Change in peanut skin prick test mean wheal diameter 
o Change in peanut component levels 
Number of 
Subjects 
30 peanut allergic subjects will be randomized 1:1 of dietary 
supplementation of a fiber supplement (RPS) versus placebo 
Diagnosis and 
Main Inclusion 
Criteria 
• 
Age 4 to 17 (inclusive) 
• 
A convincing clinical history of peanut allergy 
• 
Immune markers consistent with peanut allergy 
o 
Serum IgE to peanut of >0.35 kUA/L and a skin prick test to 
peanut >8mm greater than the negative saline control –or- 
o 
Serum IgE to peanut of >5 kUA/L and a mean peanut wheal 
diameter on skin prick test 3 to 8mm greater than the negative 
saline control –or- 
o 
Serum IgE to peanut of >14 kUA/L and mean peanut wheal 
diameter on skin prick test 3mm greater than the negative 
saline control 
• 
Experience dose-limiting symptoms at or before 100mg challenge 
dose of peanut protein on screening double blind placebo-controlled 
food challenge (DBPCFC) 
• 
Written informed consent from parent/guardian  
• 
Written assent from subjects above the ages 4-17 

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Exclusion criteria 
• 
History of a chronic disease (other than asthma, allergic rhinitis, and 
atopic dermatitis) that is at significant risk of becoming unstable or 
requiring a change in chronic therapeutic regimen 
• 
History of mast cell disease 
• 
History of recurrent idiopathic or virally induced urticaria, angioedema 
or anaphylaxis 
• 
Any history or presence of autoimmune, cardiovascular disease, 
chronic lung disease (other than asthma), malignancy, psychiatric 
illness, or gastrointestinal inflammatory conditions, including celiac 
disease, inflammatory bowel disease, eosinophilic esophagitis or other 
eosinophilic gastrointestinal disease 
• 
Current participation in any other interventional study 
• 
Subject who has undergone any type of oral immunotherapy 
• 
Severe asthma or uncontrolled mild to moderate asthma 
• 
Uncontrolled atopic dermatitis 
• 
Current use of oral steroid medications 
• 
Use of >1 bursts of oral steroid medications in the past year 
• 
Inability to eat by mouth the fiber supplementation or placebo control 
and peanut flour for any reason 
• 
Use of any therapeutic antibody (biologic medication) or any 
immunomodulatory medication in the past 12 month (other than a 
short course of oral steroids) 
• 
Current use of any type of immunotherapy 
• 
Pregnancy or lactation 
• 
Allergy to potato, corn, oat or cow’s milk  
• 
Unwillingness to carry an epinephrine autoinjector 
• 
Unwillingness to comply with activity restrictions during OIT or any 
other study procedure 
 
Study Product and 
Planned Use 
A prebiotic, resistant potato starch (RPS), will be given as a dietary 
supplement before and during oral immunotherapy to peanut 
Reference therapy 
Oral immunotherapy to peanut 
Treatment 
Description 
Subjects who meet inclusion criteria will be randomized 1:1 to receive 
either RPS or placebo. After 30 days of prebiotic therapy, subjects will 
start peanut oral immunotherapy (POIT) in addition to the prebiotic and 
continue through a prescribed course of POIT, approximately 180 days. 
After completion of POIT updosing, subjects will continue on 
maintenance POIT plus prebiotic therapy for an additional 180 days at 
which time they will undergo a DBPCFC. Subjects will then stop 
prebiotic therapy and continue on maintenance POIT in extended 
observation for approximately 4 years.  

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Schedule of Events 
• 
Inclusion/exclusion criteria  
• 
Informed consent (and assent, as age appropriate)  
• 
Medical/allergy history  
• 
Concomitant medications  
• 
Physical examination, including height and weight  
• 
Vital signs  
• 
Quality of life assessment 
• 
Spirometry (if has asthma diagnosis as COVID allows) 
• 
eNO (if has asthma diagnosis as COVID allows) 
• 
Asthma control test (ACT; if has asthma diagnosis) 
• 
Blood draw (total IgE, peanut-specific IgE, peanut component 
testing, peanut-specific IgG4, complete blood counts (CBC), 25-
hydroxyvitamin D (screening only), omega-3 index (screening 
only)) 
• 
Skin prick testing (screening and exit) 
• 
Stool collection 
• 
DBPCFC (screening and exit) 
• 
Randomization 
• 
Study product administration and dispensation for home dosing   
• 
Peanut oral immunotherapy (POIT) -in both placebo/control and 
investigational groups. 
• 
Dose compliance monitoring 
• 
Adverse event (AE) monitoring (including serious adverse 
event) 
Statistical 
Methodology 
Chi-square testing (or non-parametric equivalent) will be used to 
compare categorical variables. Student’s t-test (or non-parametric 
equivalent) will be used to compare continuous variables. Microbial 
relationships between samples will be compared using principal 
coordinate analysis and average-neighbor hierarchical clustering. 
Welch’s t-test will be used to determine significant abundance 
differences between OTUs. 
 

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1 Introduction  
1.1 Background and Rationale 
This document is a protocol for a human research study. This study is to be conducted according to US 
and international standards of Good Clinical Practice (International Conference on Harmonization 
ICHE6), the Code of Federal Regulations Title 21 parts 812, and other applicable government regulations 
and Institutional research policies and procedures.  
 
After a 50% increase in prevalence between 1997 and 2011, food allergy has become one of the most 
common chronic diseases of childhood now affecting 8% of American children, or roughly 2 children in 
every classroom in the United States.  In a similar time period, the prevalence of peanut allergy has more 
than tripled in American children.1  Children with peanut allergy have been shown to have a worse quality 
of life then children with insulin dependent diabetes mellitus and feel limited in their ability to safely attend 
social events.2  In fact more than 40% of children with peanut allergy have had a severe allergic reaction 
requiring emergency care at least once in their life, and 20% of children with peanut allergy have a 
reaction to peanut every year.1  These reactions are potentially life threatening and lead to significant 
anxiety and a financial burden for families with peanut allergic children.3  Unfortunately, children rarely 
grow out of peanut allergy naturally, and although it is a potentially fatal disease, currently, only one FDA 
approved treatment exists, oral immunotherapy (OIT) for peanut.4  
 
Oral immunotherapy is a method of inducing desensitization to peanut in those with an IgE mediated 
peanut allergy to make them “bite-safe”, or unlikely to experience a severe reaction upon the accidental 
ingestion on peanut.  When undergoing oral immunotherapy, a child is given slowly increasing doses of 
peanut that are below the threshold of reactivity that eventually induce an increasing threshold, so an 
even higher dose of peanut can be given safely.  After approximately 6 months of up-dosing, children 
become tolerant to eating one peanut a date.  After continuing to eat one peanut a day, desensitized 
children appear to undergo continued immunomodulation that raises their reactivity threshold to be 
tolerant of ingestion of 3 peanuts.4-6 
 
Unfortunately, OIT is an imperfect therapy as >70% of children undergoing therapy experience 
gastrointestinal (GI) side effects, including eosinophilic esophagitis, which has led to a significant drop out 
rate in clinical trials.  In addition, a high rate of systemic allergic reactions, that were treated with 
epinephrine, have been seen in study populations.4  Finally, little evidence exists to support using OIT as 
a cure for or to induce remission of peanut allergy, nor does evidence exist that supports the ability of 
children to “free eat” peanut in their diet after completion of therapy.  As a result, children must continue 
to take a daily dose of peanut protein for the rest of their lives in order to remain bite safe without 
expectation of any other benefit.7  
 
One barrier to the development of a more effective therapy is the lack of understanding of the 
pathogenesis of this disease. The rate of increase in peanut allergy is too high to be explained by 
genetics alone.  A theory that may, however, explain both the development and increasing prevalence of 
peanut allergy is the “microbiome hypothesis” which posits that commensal microbes or “good bacteria” in 
our gastrointestinal (GI) tract interact with our immune system through production of short chain fatty 
acids (SCFA), including butyrate, after digestion of dietary fibers.  In turn, butyrate acts as a “postbiotic” 
that influences both the development and severity of chronic non-infectious inflammatory diseases such 
as food allergy.8-10  
 
This hypothesis is supported by the vast changes in the modern lifestyle that may impact colonization of 
commensal microbes in our GI tract, including diet, antibiotic use, antiseptic use, food sterilization, smaller 
family sizes, and reduced exposure to farm animals.  The American diet is largely devoid of fibrous fruits 
and vegetables that act as prebiotic “food” for our commensal bacterial and instead high in processed 
sugars which favor growth of non-SCFA producing bacterial species.  Both antibiotics and external 
antiseptic use have been shown to influence the GI microbiome, including antibiotics fed to livestock later 

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sacrificed for meat.  Finally, the colonization or recolonization of commensal bacteria has likely been 
affected by the lack of exposure to bacteria in our day to day life.11  
As a result of this hypothesis, interest has been gained in manipulating the microbiome of the GI tract in 
order to control chronic, non-infectious inflammatory diseases, such as peanut allergy.  Prebiotic, 
probiotic and postbiotic formulations may all hold therapeutic potential.  In this trial, we propose using a 
prebiotic therapy (potato starch) previously shown to modulate the microbiome in adults in children with 
peanut allergy to determine if it has an effect on the commensal bacteria of the GI tract and subsequently 
influences the immune response.12      
 
 
Murine model studies have demonstrated that both germ free mice and mice treated with a cocktail of 
antibiotics, beginning pre-weaning, are highly susceptible to allergic sensitization to food10. Studies 
involving selective colonization of gnotobiotic mice demonstrate that mucosa-associated Firmicutes in the 
Clostridia class protect against allergic sensitization by inducing IL-22 dependent barrier protective 
responses in the intestine that limit systemic access of allergenic food proteins10,12.  Numerically, 
Firmicutes (which includes Clostridia) are a dominant component of the gut microbiota13,14.  Many 
Clostridia are involved in the complex process of digesting fiber and resistant starches. This process 
involves sequential breakdown by particular bacterial taxa and ultimately results in the formation of short 
chain fatty acids (SCFAs). SCFAs have potent immunomodulatory effects correlated with host health15,16 
including induction of colonic regulatory T cells and improvement of allergy symptoms in a mouse 
model17,18. Butyrate, in particular, is an important energy source for colonic epithelial cells19. Butyrate 
drives oxygen consumption by colonocytes through b-oxidation, which maintains a locally hypoxic niche 
for butyrate-producing obligate anaerobes20. Induction of SCFA production may therefore be a key 
component of Clostridia’s allergy-protective effect. 
 
Initial translational studies established that the composition of the fecal microbiota is altered (and butyrate 
production is reduced) in infants with cow’s milk allergy21. Feehley et al. demonstrated that there were 
numerous differentially abundant bacterial operational taxonomic units (OTUs) between healthy and CMA 
infants or GF mice colonized with the feces of these infants22.  Analysis of differentially abundant OTUs 
that distinguished the CMA and healthy populations in both the human donors and colonized mice. 
Correlation of ileal taxa with differentially expressed genes in the ileum of healthy-colonized mice 
identified a Clostridial species, Anaerostipes caccae, that mimicked the effects of the healthy microbiota, 
supporting a causal role for a specific bacterial taxon in protection against food allergy. A. caccae is an 
extremely efficient butyrate producer commonly found in the infant gut but can be identified in adults as 
well23,24. 
 
More recently, evidence expands this observation beyond infants. Identification of differentially abundant 
OTUs in healthy and allergic twins revealed that 84% were in the Clostridia class25. These bacterial OTUs 
were then correlated with fecal metabolites from nonbiased metabolomic profiling, which identified 
another potentially protective Clostridial species in healthy twins: R. bromii. R. bromii is measurable in the 
feces of many (but not all) adults and is recognized as a keystone species for the degradation of type III 
resistant starches, like resistant potato starch (RPS)26. R. bromii abundance in feces significantly 
increases upon dietary intervention with RPS27,28. Individuals that do not have detectable R. bromii in the 
feces before beginning a RPS-supplemented diet consume about 40% less total starch than individuals 
colonized with R. bromii, demonstrating that this species alone is responsible for much of the total starch 
digestion in the colon27. R. bromii performs the initial phases of resistant starch digestion, producing 
intermediate metabolites such as acetate which can then be consumed by butyrate producing bacteria. 
While R. bromii is not capable of producing butyrate itself, a recent report demonstrated that two weeks of 
RPS consumption by young adults was sufficient to induce detectable increases of butyrate in feces29. 
This increase in butyrate concentration was greater in individuals who also demonstrated increased fecal 
abundance of R. bromii compared to those with no change. Butyrate concentration was also significantly 
correlated with changes in the abundance of Eubacteriium rectale, a well characterized butyrate 
producing Clostridia29. Interestingly E. rectale is one of the few bacterial species detectable in the 
microbiomes of most healthy individuals worldwide30. Taken together the data suggest that R. bromii is a 
tractable biomarker, associated with a healthy microbiota and increased butyrate production, and 
responsive to dietary intervention. Interestingly, and in agreement with our hypothesis, the Canadian 

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Healthy Infant Longitudinal Development birth cohort study reported that depletion of R. bromii early in life 
(3 and 12 months of age) is associated with the development of atopy and reduced genetic potential to 
produce butyrate31.  
 
Due to the existing limitations of OIT, multiple strategies of combination therapy to reduce symptoms 
associated with treatment and induce remission or prolonged non-responsiveness have been trialed, but 
each have significant limitations thus far. Combining the IgE-blocking antibody omalizumab with peanut 
OIT reduces adverse reactions initially, but these adverse events return after stopping omalizumab 
treatment and to date the cost associated with omalizumab has limited its utility in the clinical setting32. 
Microbial therapies have also recently been studied in combination with OIT in both preclinical and clinical 
settings33. Both prebiotics (bacteriaaccessible carbohydrates) and probiotics (live bacteria themselves) 
can improve allergic responses to food in mouse models16,33,34. Further, the combination therapy of OIT 
plus Lactobacillus rhamnosus GG (LGG), a bacterial species that when supplemented in infant formula 
increases the abundance of butyrate-producing bacteria in feces, demonstrated improved efficacy of OIT 
compared to previous studies and showed potential for inducing remission at 2-5 weeks and up to four 
years after discontinuing treatment21,35,36. However, this study lacked appropriate controls preventing 
adoption of the approach.  
 
In a series of publications, the beneficial effects of both the Clostridia class (as a whole) as well as 
individual species (A. caccae and R. bromii) has been shown in protection against food allergy in humans 
and gnotobiotic mice. The candidate species that we have identified may work together in the process of 
fiber digestion to produce butyrate. As mentioned above, others have shown that a significant expansion 
of R. bromii upon dietary supplementation with RPS correlates with increased concentrations of fecal 
butyrate28,29. We now seek to extend these findings by using RPS as an additive therapy for peanut 
allergic children undergoing POIT. We predict that the high incidence of GI symptoms and systemic 
allergic reactions during POIT may be due, in part, to the fact that POIT is administered without any 
strategy to address intestinal barrier dysfunction in allergic subjects. We predict that administering RPS 
prior to and during POIT will expand populations of protective bacteria, elicit a bacteria-induced barrier 
protective response, and improve clinical outcomes of POIT.  
     
1.2 Investigational Food 
 
The following foods will be used: 
• 
Resistant potato starch (RPS) 
• 
Corn starch (as placebo) 
 
1.3 Preclinical Data 
 
Murine models have shown that the GI microbiota affect allergic sensitization.  When mice are raised in a 
germ-free environment, gut associated lymphoid tissue are poorly developed and have lower levels of IgA 
and IL-10 secreting T regulatory cells, important for oral tolerance.  In fact, these mice raised in a germ-
free environment are unable to be tolerized to oral antigens.  However, when certain bacteria or bacterial 
components are introduced into germ-free mice, these observations are reversed.  Introduction of B 
fragilis or LPS into germ-free mice can redevelop GALT and induce oral tolerance.  In addition, 
introduction of certain butyrate-producing Clostridium species can increase T regulatory cells and protects 
against peanut allergic sensitization.10  Finally, transfer of gut microbiota from food allergic mice into 
germ-free mice increases the germ-free mice’s susceptibility to food allergy; while, transfer of stool from 
healthy infants, but not milk-allergic infants, protects against anaphylactic responses to cow’s milk.22 
 
One study has looked at the effect of high fiber diet on oral tolerance and the development of food allergy 
in mice.  In this study, mice were fed a high fiber diet containing cellulose and guar gum.  The diet 
reshaped the gut microbial ecology and increased the release of SCFAs, including butyrate.  This, in turn, 
enhanced oral tolerance and protected against food allergy.18 

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1.4 Clinical Data to Date 
 
One recent single center study compared the dynamics of the gut microbiota and SCFA in response to 2-
week dietary interventions with three fibers, resistant starch from potato (RPS), resistant starch from 
maize (RMS), inulin from chicory root with an accessible corn starch (ACS) used as a control.  This study 
found that RPS resulted in the increase in total SCFAs, including butyrate.  In addition, RPS caused an 
increase in relative abundance of bifidobacteria and the butyrate producing Ruminococcus bromii and 
Clostridium chartatabidum.29  The benefits of RPS have similarly been shown in several other chronic, 
non-infectious inflammatory diseases, including obesity, diabetes and inflammatory bowel disease.37-39 
1.5 Risks/Benefits 
 
Risks Associated with RPS and placebo (corn starch) 
RPS is a food product and generally regarded as safe (GRAS) by the following. Under sections 201(S) 
and 409 of the Federal Food, Drug, and Cosmetic Act, “any substance that is intentionally added to food 
is a food additive, that is subject to premarket review and approval by FDA, unless the substance is 
generally recognized, among qualified experts, as having been adequately shown to be safe under the 
conditions of its intended use, or unless the use of the substance is otherwise excepted from the 
definition of food additive. Under sections 201(s) and 409 and FDA’s implementing regulations in 21 CFR 
170.3 and 21 CFR 170.30, the use of a food substance may be GRAS either through scientific 
procedures or, for a substance used in food before 1958, through experience based on common use in 
food Under 21 CFR 170.30(b), general recognition of safety through scientific procedures requires the 
same quantity and quality of scientific evidence as is required to obtain approval of the substance as a 
food additive.  General recognition of safety through scientific procedures is based upon the application of 
generally available and accepted scientific data, information, or methods, which ordinarily are published, 
as well as the application of scientific principles, and may be corroborated, by the application of 
unpublished scientific data, information, or methods.” GRAS notice 310 claims exemption from the 
requirement of premarket approval for potato fiber and was closed on 12-24-2009 with no questions from 
the FDA.  In addition, under 21 CFR 170.30(c) and 170.3(f), general recognition of safety through 
experience based on common use in foods requires a substantial history of consumption for food use by 
a significant number of consumers.  Potatoes have been commonly consumed throughout history by 
numerous populations.   
 
In this study, we are enrolling subjects between the ages of 4 and 17, inclusive with peanut allergy and 
asking them to consume either a RPS or a control starch (corn starch).  This consumption of either 
product may increase the overall caloric intake of subjects which may lead to weight gain.  Subjects in the 
RPS group will be asked to consume 1 tablespoon (12 grams) of a fiber supplement daily which contains 
40 calories/tablespoon.  Subjects in the control group will be asked to consume 1 tablespoon (8 grams) of 
ACS daily which contains 30 calories/tablespoon.  In addition, an increase in fiber consumption may lead 
to bloating, gas and/or constipation. 
 
Risks Associated with DBPCFC 
 
In this study DBPCFCs will be conducted in accordance with the recommended PRACTALL guidelines.  
The screening DBPCFC is utilized as the standard of care to confirm peanut allergy and does not confer 
higher then minimal risk then a open label food challenge used clinically to confirm peanut allergy priori to 
POIT. The screening DBPCFC will also establish a threshold for reactivity for comparison with the exit 
DBPCFC.  The exit DBPCFC will be used to establish efficacy of POIT and confirm safety of accidental 
ingestion of peanut.  The exit DBPCFC also does not confer more than minimal risk above a standard of 
care open label food challenge used during POIT to confirm tolerance of peanut ingestion.  DBPCFC are 
expected to induce allergic reactions. Reactions range from mild (nausea, few hives) to severe 
(wheezing, diffuse urticaria, rhinitis/conjunctivitis, vomiting/diarrhea, impending doom) to potentially life 
threatening (low blood pressure, difficulty breathing, neurologic changes). Administered in a controlled 
setting under the supervision of experienced staff, food challenges are considered safe and are the 

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current gold standard for the diagnosis of peanut allergy. As soon as symptoms consistent with an allergic 
reaction are witnessed, interventions to stop the reaction are begun (H1 antihistamines and epinephrine).  
 
Risks Associated with POIT 
The most common side effect associated with POIT is GI symptoms, including stomach pain and mouth 
itching. These are expected to occur in nearly 2/3 of individuals.  These symptoms tend to be transient in 
nature and typically occur in the first few days after up-dosing POIT and for the first hour after taking the 
dose. GI symptoms are mitigated by eating large meal with each dose and staying well hydrated. 
Symptoms will be controlled with H1-antihistamines as needed.  Systemic allergic reactions/anaphylaxis 
is also a side effect of POIT. This risk is mitigated by restricting physical activity, hot showers, and NSAID 
use for 3 hours after daily dosing of POIT. Should symptoms occur, they will be treated with epinephrine.  
All participants will be required to carry an epinephrine autoinjector. POIT may also be associated with 
eosinophilic esophagitis.  The reported incident is <1% and typically resolves with removal of peanut 
protein exposure. 
 
Risks Associated with Blood Draw 
All subjects enrolled in the study will be asked to undergo a blood draw.  The risks involved in drawing 
blood from a vein may include, but are not limited to, momentary discomfort at the site of the blood draw, 
possible bruising, redness, and swelling round the site, bleeding at the site, feeling of lightheadedness 
when the blood is drawn, and rarely, an infection at the site of the blood draw.  In order to minimize these 
risks, blood draws will be done under hygienic conditions by experienced personnel. 
 
Potential benefits of Prebiotic Fiber 
The potential benefits of consuming a fiber supplement include reducing constipation, maintaining a 
healthy weight, lower blood sugar and cholesterol levels.  The theoretic benefit to consuming a fiber 
supplement is that it may improve tolerance of oral immunotherapy to peanut and/or improve 
immunologic markers associated with peanut allergy.  No additional benefit is hypothesized from the 
control fiber.  
 
Benefits of Oral Immunotherapy (OIT) 
The benefit of undergoing peanut OIT is that subjects become “bite-safe” in case of an accidental 
ingestion of peanut protecting them from a severe, systemic allergic reaction. 
2 Study Objectives 
2.1 Primary Objective 
 
The primary objective of this study is to determine if prebiotic therapy improves outcomes and reduces 
side effects associated with POIT. 
2.2 Secondary Objective(s) 
 
The secondary objectives of this study are: 
• 
To determine if prebiotic therapy influences the gut microbiome/metabolome 
• 
To determine if prebiotic therapy influences immunological markers associated with peanut 
allergy 
3 Study Design 
3.1 General Design 
This study is a randomized, double-blind, placebo controlled, single center clinical trial.  Subjects are 
anticipated to be in this study for 1 year with extended, active monitoring for an additional 4 years.  After 
enrollment, screening and randomization, patients will be assigned to consume either RPS or placebo for 

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30 days.  At the end of the 30 days, patients will begin the standard of care treatment for peanut allergy, 
peanut oral immunotherapy.  Initial dose escalation and up-dosing of POIT plus prebiotic will take 
approximately 180 days to complete.At the end of the maintenance phase, subjects will undergo a 
DBPCFC to determine efficacy of treatment. Finally, patients will be monitored for approximately 4 year 
following completion of the active drug dosing (off prebiotic) therapy during the continued 
immunomodulation/extended maintenance phase of POIT. 
 
Description of DBPCFC 
DBPCFC will be conducted in accordance with PRACTALL guidelines and utilize either peanut flour 
(Anthony’s Organic Peanut Flour ) or placebo (Oat Flour; Bob’s Red Mill) as previously described.  Food 
challenges will be conducted on two separate days no more than 7 days apart and no more than 30 days 
prior to initial dose escalation day (for the screening food challenge).  Prior to the food challenges, 
patients will be instructed to stop all antihistamines for 5 days prior to each challenge.  All subjects will be 
free from asthma or atopic dermatitis flare.  Asthma will be assessed by auscultation for active wheeze 
prior to start of the challenge and a peak expiratory flow of greater than or equal to 80% of personal best 
value.  Atopic dermatitis flare will be assessed by investigator examination.  Subjects will be admitted to 
the University of Chicago special procedure unit for initial dose escalation where walls are transparent 
glass for continuous observation by trained nursing staff.  The special procedure area is located 
immediately above a pediatric dedicated emergency department.  Subjects will be monitored on a 
continuous heart rate and oxygen saturation monitor throughout the procedure.  Intramuscular 
epinephrine and oral antihistamines will be in the room with the patient prior to initiation of any doses.  
The patient’s temperature and blood pressure will be checked before each dose.  A resuscitation cart will 
be available within the area.  A resuscitation team will be available within the hospital. Peanut flour and 
placebo will be mixed in either chocolate pudding and peppermint extract or applesauce and cinnamon to 
mask flavor and nose clips (as tolerated by the child) will be utilized during consumption to mask flavor.  A 
second bite of vehicle will be given that does not contain challenge material followed by a sip of water 
prior to removal of nose clips (if nose clips can be utilized).  Doses will be given every 15-20 minutes at 
the following doses:  1mg, 3mg, 10mg, 30mg, 100mg, 300mg (exit only), 600mg (exit only), 1000mg (exit 
only) peanut protein.  Peanut protein constitutes half the peanut flour by weight, thus both peanut and oat 
flour will be administered in the following weights: 2mg, 6mg, 20mg, 60mg, 200mg, 600mg (exit only), 
1200mg (exit only), 2000mg (exit only).  Subjects will be monitored for at least 2 hours beyond resolution 
of symptoms but this period may be extended at the discretion of the investigator.   
 
Reactions will be determined in the following way.  Symptoms will be considered consistent with a 
reaction and the food challenge stopped if the subject experiences any moderate or severe symptoms 
outlined below.  The food challenge will be stopped if the subject experiences two of more mild, 
symptoms.  If the subject experiences one mild subjective symptom, the dose will be repeated before 
escalation.  
 
Mild Symptoms: 
Skin: limited (few) or localized hives, mild swelling, mild skin flushing or mild pruritus (only occasional 
scratching) 
Respiratory: rhinorrhea, nasal congestion, occasional cough, throat discomfort 
Gastrointestinal: mild nausea abdominal discomfort, a single minor vomiting episode and/or a single 
episode of diarrhea 
 
Moderate symptoms: 
Skin: systemic hives, significant swelling, pruritus causing protracted scratching, more than a few areas of 
erythema or pronounced erythema 
Respiratory: throat tightness without hoarseness, persistent cough, wheezing without dyspnea 
GI: persistent moderate abdominal pain/cramping/nausea, more than a single episode of vomiting and/or 
diarrhea 
 
Severe symptoms: 
Skin: severe generalized urticaria/angioedema/erythema 
Respiratory: laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea, stridor 

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GI: severe abdominal pain/cramping/repetitive vomiting and/or diarrhea 
Neurological: change in mental status 
Circulatory: clinically significant hypotension 
 
 
 
 
Description of POIT 
Anthony’s Organic Peanut Flour  will be utilized for POIT, and doses will be prepared by the study PI or 
by trained study staff under direct supervision of the PI.  Peanut flour will be mixed into water to form a 
slurry and delivered via a medication syringe to optimize at home dosing until doses are sufficiently high 
to be measured with standard kitchen utensils (i.e. 1/8 teaspoon). Throughout the course of POIT, 
patients will be instructed to eat a large meal before every dose and will also be instructed to abstain for 
any activity that will increase his/her heartrate for 3 hours following each dose, including physical activity 
(other than light walking) and hot showers.  No sleep will be allowed during this observation period.  
Patients will be asked to avoid use of nonsteroidal anti-inflammatory medications throughout the course 
of oral immunotherapy (acetaminophen will be allowed).  No updosing will occur in menstruating women 
during menses.  If a patient develops a fever (T > 100°F), asthma flare, or gastrointestinal illness during 
the course of POIT, dosing will be help for up to two days and restarted upon fever resolution at home.  If 
a fever lasts longer than two days, patients will return to clinic to restart.  If more than 2 consecutive days 
of doses (but less than 7 days) are missed at any time during POIT for any reason (including fever), 
patients will be restarted at 50% of their current dose under supervision of the investigator but allowed to 
return to current dosing at home at the discretion of the investigator in 2-4 days.  If 7 or more consecutive 
days of doses are missed, POIT will be restarted under supervision of the investigator at less than 50% of 
the current dose with a modified updosing schedule. 
 
For initial dose escalation, patients will be instructed to eat a large meal prior to arrival in clinic then eat 
snacks throughout the morning.  Patients will be admitted to the University of Chicago special procedure 
unit for initial dose escalation where walls are transparent glass for continuous observation by trained 
nursing staff.  Patients will be monitored on a continuous heart rate and oxygen saturation monitor 
throughout the procedure.  Intramuscular epinephrine and oral antihistamines will be in the room with the 
patient prior to initiation of any doses.  The patient’s temperature and blood pressure will be checked 
before each dose.  A resuscitation cart will be available within the area.  Patients will be dosed every 20 
to 30 minutes.  Doses given on initial dose escalation day are as follows: 0.5mg, 1mg, 1.5mg, 3mg, 6mg 
of peanut protein.  If patients tolerate at least 3mg on initial dose escalation, they will return the following 
day for their first monitored dose of 3mg.  If the patient tolerates, the 3mg the will continue this dose daily 
for two weeks then return for updosing.  The updosing schedule will be as follows: 3mg, 6mg, 12mg, 
20mg, 40mg, 80mg, 100mg, 125 mg, 150 mg, 250 mg, 300 mg.  If the patient is experiencing 
gastrointestinal side effects that do not subside prior to updoing in 2 weeks, updosing may be delayed 
from 1 week to indefinitely until side effects improve and at the discretion of the investigator.  If POIT is 
discontinued for any reason, patients will continue to be observed on study but not undergo the final 
DBPCFC (unless the patient withdraws from the study).  Patients will continue on 300mg dosing until the 
end of study at which time they may choose to consent to an extended maintenance study or follow up 
with their allergist for continued standard of care monitoring and dosing.  
 

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3.2 Primary Study Endpoints 
The primary endpoint is the proportion of subjects who tolerate at least 1043 mg cumulative of peanut 
protein with no more than mild symptoms at the 12 month DBPCFC 
3.3 Secondary Study Endpoints 
The secondary endpoints are as follows: 
• 
To determine the proportion of subjects who experience dose related GI side effects during oral 
immunotherapy 

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• 
To determine the proportion of subjects who experience hypersensitivity reactions (other than GI) 
during oral immunotherapy 
 
The exploratory endpoints are as follows: 
• 
To demonstrate the effect of resistant potato starch (RPS) on the fecal microbiome and 
metabolome 
• 
To determine if gnotobiotic mice colonized with the fecal microbiota of study participants models 
clinical response 
• 
To evaluate the immunological effects of fiber supplementation in children 
o 
Change in peanut specific IgE and IgG4 levels 
o 
Change in peanut skin prick test mean wheal diameter 
o 
Change in peanut component levels 
4 Subject Selection and Withdrawal 
4.1 Inclusion Criteria 
The following criteria are used to determine eligibility for the trial: 
• 
Age 4 to 17 (inclusive) 
• 
A convincing clinical history of peanut allergy 
• 
Immune markers consistent with peanut allergy 
o 
Serum IgE to peanut of >0.35 kUA/L and a skin prick test to peanut >8mm greater than 
the negative saline control –or- 
o 
Serum IgE to peanut of >5 kUA/L and a mean peanut wheal diameter on skin prick test 3 
to 8mm greater than the negative saline control –or- 
o 
Serum IgE to peanut of >14 kUA/L and mean peanut wheal diameter on skin prick test 
3mm greater than the negative saline control 
• 
Experience dose-limiting symptoms at or before 100mg challenge dose of peanut protein on 
screening double blind placebo-controlled food challenge (DBPCFC) 
• 
Written informed consent from parent/guardian  
• 
Written assent from subjects above the age of 7 
• 
Fully vaccinated against COVID-19 
4.2 Exclusion Criteria 
The following are criteria used to determine eligibility for the trial: 
• 
History of a chronic disease (other than asthma, allergic rhinitis, and atopic dermatitis) that is at 
significant risk of becoming unstable or requiring a change in chronic therapeutic regimen 
• 
History of mast cell disease 
• 
History of recurrent idiopathic or virally induced urticaria, angioedema or anaphylaxis 
• 
Any history or presence of autoimmune, cardiovascular disease, chronic lung disease (other than 
asthma), malignancy, psychiatric illness, or gastrointestinal inflammatory conditions, including 
celiac disease, inflammatory bowel disease, eosinophilic esophagitis or other eosinophilic 
gastrointestinal disease 
• 
Current participation in any other interventional study 
• 
Subject who has undergone any type of oral immunotherapy 
• 
Severe asthma or uncontrolled mild to moderate asthma 
• 
Uncontrolled atopic dermatitis 
• 
Current use of oral steroid medications 
• 
Use of >1 bursts of oral steroid medications in the past year 
• 
Inability to eat by mouth the fiber supplementation or placebo control and peanut flour for any 
reason 
• 
Use of any therapeutic antibody (biologic medication) or any immunomodulatory medication in the 
past 12 month (other than a short course of oral steroids) 
• 
Current use of any type of immunotherapy 

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• 
Pregnancy or lactation 
• 
Allergy to potato or corn 
• 
Unwillingness to carry an epinephrine autoinjector 
• 
Unwillingness to comply with activity restrictions during OIT or any other study procedure   
 
4.3 Subject Recruitment and Screening 
 
Subjects will be recruited for this trial in several ways 
1. A letter and attached flier will be sent to those enrolled in the University of Chicago Allergy and 
Asthma Research Registry 
2. A short description will be posted in social media 
3. Patients will be approached during clinic visits to the Allergy/Immunology clinic at the University of 
Chicago 
4. Fliers will be sent to outside allergists 
 
Subjects who respond to advertisement will first undergo a prescreen to confirm inclusion and exclusion 
criteria.  Those who meet criteria will be invited in for a screening visit where skin testing, spirometry, 
blood draw, and questionnaire will be administered.  Those who meet criteria after the screening visit will 
be randomized and enrolled. 
4.4 Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
Subjects may be withdrawn from this study at any time.  Subjects may be withdrawn from the study prior 
to the completion of the study by the subject for safety reasons, failure of the subject to protocol 
requirements, subject consent withdrawal.  Abrupt withdrawal from this study poses no additional risk to 
the subject.  
4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
Even if subjects withdraw or are withdrawn prematurely from the study, data from the electronic medical 
record may continue to be used and patients may continue to be contacted, periodically by phone to 
determine if the patient has suffered any adverse events from withdrawal from the study if subjects allow 
contact to continue. 
5 Study Food  
5.1 Description 
The following foods will be used: 
• 
Fiber supplement: resistant potato starch 
• 
Placebo: corn starch 
5.2 Treatment Regimen 
Subjects will be asked to take 1 tablespoon of fiber supplement (or placebo daily) mixed with a liquid or 
semi-solid food, such as pudding, applesauce or guacamole.  If the supplementation causes abdominal 
distress, the participants will be asked to cut the dose in half for one week then increase back to the full 
tablespoon dose. 
5.3 Method for Assigning Subjects to Treatment Groups 
Subjects will be randomly assigned to either the treatment or placebo.  Randomization will be conducted 
by IDS pharmacy . Study staff will be blinded throughout the course of the study. Subject compliance will 

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be monitored by subject/parent self-report in paper diary provided to the subject at the start of the study 
as well weight of returned investigational product.  
5.4 Prior and Concomitant Therapy 
Subject will be asked to discontinue any daily antihistamine use. However, subjects will be allowed to use 
oral antihistamines on an as needed basis.  A record of all current medications will be kept from the start 
to the completion of the study.  A record of medications taken to manage POIT related side effects will be 
monitored in a daily diary. All study participants will be required to have an epinephrine autoinjector 
throughout the duration of the study.  If the study participant is unable to obtain a new epinephrine 
autoinjector after the expiration, use or loss of a current epinephrine autoinjector, every effort will be 
made by the Principal Investigator to obtain one for the subject; however, if one cannot be obtained, the 
subject may be withdrawn from the study. 
 
Please see exclusion criteria for medications not allowed during this study. 
5.5 Packaging 
The study food will be transferred from the original packaging into a sealed plastic container appropriately 
labeled.   
5.6 Blinding of Study 
Neither the study participant nor the study team will be aware of the contents of the sealed plastic 
container provided to the study participant2 
 Only the study pharmacist will have access to the form which links each study participant to their 
respective groups.  The investigational product and placebo will be stored at the University of Chicago 
IDS pharmacy at:  
5835 South Cottage Grove 
CCD Room 2-520, MC 0010 
Chicago IL, 60611 
 
 
5.7 Storage, Dispensing and Return 
5.7.1 Storage 
The study food may be stored at room temperature but should not be subject to extreme hot or cold.  The 
study food should remain in the provided contained throughout the duration of the study.  If the contents 
of the contained spill or become contaminated, the investigators will provide a new container of study 
food to the participant. 
5.7.2 Return or Destruction of Study Device 
At the completion of the study, any remaining study food will be returned to the investigator, and there will 
be a final reconciliation of the study food by weighing the container and its contents.  All remaining study 
food will be destroyed by the IDS pharmacy. 
6 Study Procedures 
6.1 Visit 1 
• 
Informed consent/assent 
• 
Medical/allergy history 
• 
Concomitant medications 
• 
Vital signs 
• 
Physical examination, including height and weight 

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• 
Quality of life assessment 
• 
Spirometry (if has asthma diagnosis; as COVID allows) 
• 
eNO (if has asthma diagnosis; as COVID allows) 
• 
ACT score (if has asthma diagnosis; as COVID allows) 
• 
Skin prick testing 
• 
Blood draw 
• 
Stool sample kit given 
6.2 Visits 2 and 3 (within 4 weeks of visit 1) 
• 
Stool sample collection (visit 2 only) 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
Spirometry (if has asthma diagnosis; as COVID allows) 
• 
DBPCFC 
• 
Randomization 
• 
Prebiotic dispense 
6.3 Visit 4 (30 days after visit 3) 
• 
Interval medical history 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
Spirometry (if has asthma diagnosis as COVID allows) 
• 
Skin prick testing 
• 
Blood draw 
• 
Stool sample collection 
• 
Collection of dose and symptom logs  
• 
Standard of care consent for POIT 
• 
POIT initial dose escalation day 
6.4 Visits 5 (day after visit 4) 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
POIT 3mg dose start 
6.5 Visits 6-14 (every 2-4 weeks) 
• 
Interval medical history 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
Stool sampling (monthly) 
• 
Collection of logs 
6.6 Visit 15 (3 months after visit 14) 
• 
Interval medical history 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
Stool sample collection  
• 
Collection of logs 
 
Visit 15 (3 months after visit 14; virtual) 
• 
Interval medical history 

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• 
Height and weight  
• 
Stool sample collection  
• 
Collection of logs 
6.7 Visits 16 and 17 (3 months after visit 15)  
• 
Interval medical history (visit 16 only) 
• 
Vital signs 
• 
Physical examination, including height and weight 
• 
Stool sample collection (visit 16 only) 
• 
Skin prick test (visit 16 only) 
• 
Blood draw (visit 16 only) 
• 
Spirometry (if has asthma diagnosis; as COVID allows) 
• 
DBPCFC 
7 Statistical Plan 
7.1 Sample Size Determination 
As this study is an exploratory, pilot study we will enroll 30 subjects. 
7.2 Statistical Methods 
Chi-square testing (or non-parametric equivalent) will be used to compare categorical variables. Student’s 
t-test (or non-parametric equivalent) will be used to compare continuous variables. Microbial relationships 
between samples will be compared using principal coordinate analysis and average-neighbor hierarchical 
clustering. Welch’s t-test will be used to determine significant abundance differences between OTUs. 
8 Safety and Adverse Events 
8.1 Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Unanticipated Serious Adverse Event  
An Unanticipated Effect is any serious adverse effect on health or safety, or any life-threatening problem 
or death caused by, or associated with the study food, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated with a study 
food that relates to the rights, safety, or welfare of subjects. 
 
Serious Adverse Event 
Any injury or illness that is any one of the following:  
• death 
• life-threatening (at the opinion of the investigator an immediate risk of death occurred) 
• results in permanent impairment of a body function or permanent damage to body structure 

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• necessitates medical or surgical intervention to preclude permanent impairment of a body function 
or permanent damage to a body structure 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries will be regarded as adverse events.  
Abnormal results of diagnostic procedures (including DBPCFC) are considered to be adverse events if 
the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• leads to additional treatment other than epinephrine, antihistamines and corticosteroids or to 
further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
Adverse Event Severity 
The investigator will assign severity grades to adverse events.  Adverse events will be graded using the 
CoFAR grading system as follows: 
 
Grade 1 (mild): transient or mild discomforts (<48 hours); no or minimal medical intervention/therapy 
required.  For allergic reactions, these symptoms may include pruritus, swelling, or rash, abdominal 
discomfort or other transient symptoms. 
 
Grade 2 (moderate): symptoms that produce mild to moderate limitation in activity that may require some 
assistance; no or minimal intervention/therapy is required; hospitalization is possible.  For allergic 
reactions, these symptoms may include persistent hives, wheezing without dyspnea, abdominal 
discomfort/increased vomiting or other symptoms 
 
Grade 3 (severe): marked limitation in activity that usually requires some assistance usually; medical 
intervention/therapy required; hospitalization is possible.  For allergic reactions, symptoms may include 
bronchospasm with dyspnea, severe abdominal pain, throat tightness with hoarseness, transient 
hypotension among others.  Parenteral medications are usually indicated. 
 
Grade 4 (life-threatening): extreme limitation in activity that requires significant assistance; significant 
medical/therapy or intervention is required; hospitalization is probable.  Symptoms may include persistent 
hypotension and/or hypoxia with resultant decreased level of consciousness associated with collapse 
and/or incontinence or other life threatening symptoms. 
 
Grade 5 (death): death  
8.2 Recording of Adverse Effects 
At each contact with the subject, the investigator will seek information on adverse effects of the fiber 
supplementation by specific questioning and, as appropriate, by examination.  Information on all adverse 
effects will be recorded immediately in the source document, and also in the case report form (CRF).  All 
clearly related signs, symptoms, and abnormal diagnostic procedures results should recorded in the 
source document, though should be grouped under one diagnosis. 
 
The clinical course of each event will be followed until resolution, stabilization, or until it has been 
determined that the study treatment or participation is not the cause.  Serious adverse events that are still 
ongoing at the end of the study period will be followed up to determine the final outcome.  Any serious 
adverse device effects that occur after the study period will be recorded and reported promptly (see 
section 8.3 below). 
 
The minimum initial information that will be captured in the subject’s source document concerning the 
adverse event includes:  

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• 
Study identifier 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Investigator assessment of the association 
between the event and study treatment 
• 
Current status 
• 
Whether study treatment was discontinued 
• 
Whether the event is serious and reason for 
classification as serious 
 
8.3 Reporting of Adverse Events and Unanticipated Problems 
Researchers will submit reports of the following problems within 10 working days from the time the 
investigator becomes aware of the event: 
Any adverse event that occurs any time during or after the research study, which in the opinion of 
the principal investigator is: 
• Unexpected (An event is “unexpected” when its specificity and severity are not accurately 
reflected in the protocol-related documents, such as the IRB-approved research protocol, any 
applicable investigator brochure, and the current IRB-approved informed consent document and 
other relevant sources of information, such as product labeling and package inserts.) 
AND 
• Related to the research procedures (An event is “related to the research procedures” if in the 
opinion of the principal investigator or sponsor, the event was more likely than not to be caused 
by the research procedures.) 
The above will be completed regardless of whether the event is serious or non-serious, on-site or 
off-site 
 
Protocol Deviations 
Any protocol deviations initiated without the The University of Chicago IRB approval that may affect the 
scientific soundness of the study, or affect the rights, safety, or welfare of study subjects, will be reported 
to the IRB as soon as a possible, but no later than 5 working days of the protocol deviation. 
8.4 Medical Monitoring 
The Principal Investigator will oversee the safety of the study at the site. This safety monitoring will 
include careful assessment and appropriate reporting of adverse events. 
8.4.1 Data Monitoring Board 
A Data Safety Monitoring Board (DSMB) will monitor the safety of the study.  The DSMB will continually 
review safety data and halt the study for any substantial imbalance in adverse events.  Full details are 
provided in the DSMB charter. 
 
8.4.2 Overall Stopping Rules 
This study will be suspended at any time if a study related death occurs in a subject on active therapy or 
upon the hospitalization of the second of two study related hospitalizations.  If the study is suspended, 
screening, enrollment and POIT increases will immediately stop but active subjects will continue on 
current dosing unless otherwise directed by the FDA.  The study and POIT dose escalation will not 
resume until discussed with the DSMB and FDA.   
8.4.3 Individual Stopping Rules 
Individuals may stop participation at any time for any reason, including inability to tolerate study related 
side effects.  If individuals discontinue either study drug treatment or POIT treatment at their discretion 
or because they meet an individual stopping rule, they will continue to be monitored for the length of 

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the study unless the subject withdraws consent. Subjects will not undergo a DBPCFC at exit unless the 
subject reaches POIT maintenance dosing of 300mg peanut protein for 6 months.  
 
Specific individual stopping rules are as follows:  
 
1. A subject misses 5 or more consecutive days of POIT or study drug dosing due to non-
compliance (but not illness)  
 
2. The subject misses 14 consecutive days of POIT or study drug dosing for any reason  
 
3. Administration of three or more doses of epinephrine as a result of an allergic reaction caused 
by a single POIT dose 
 
4. Meeting any exclusion criteria during the course of the study 
 
5. Development of eosinophilic esophagitis (biopsy proven)  
 
6. Any reason at the discretion of the investigator that continued participation in this study places 
the subject at unacceptable risk or for any reason prevents safe conduct of the study.   
 
In this study, if a subject fails to tolerate an updose after 3 or more attempts but do not meet the 
aforementioned stopping criteria, the subject will continue maintenance dosing at the last tolerated 
dose indefinitely.  Failure to tolerate an updose after 3 or more attempts is not an individual stopping 
rule for purposes of this study.  
 
9 Data Handling and Record Keeping 
9.1 Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of 
the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
9.2 Source Documents 
Source documents for this study will include (but is not limited to) hospital records (EPIC), case report 
forms, subject diaries as well as questionnaires.   
9.3 Case Report Forms 
All data requested on the case report form (CRF) will be recorded, and all missing data will be explained.  
If a space on the CRF is left blank because the procedure was not done or the question was not asked, 

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“N/D” will be written.  If the item is not applicable to the individual case, “N/A” will be written.  All entries 
will be printed legibly in black ink.  If any entry error has been made, to correct such an error, a single 
straight line will be drawn through the incorrect entry and the correct data will be written above it.  All such 
changes will be initialed and dated. 
9.4 Records Retention 
All essential documents will be retained for at least 2 years after completion of the study. 
 
10 Ethical Considerations 
This study will be conducted according to US and international standards of Good Clinical Practice (FDA 
Title 21 part 312 and International Conference on Harmonization guidelines), applicable government 
regulations and Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted Institutional Review Board 
(IRB), in agreement with local legal prescriptions, for formal approval of the study conduct.  The decision 
of the IRB concerning the conduct of the study will be made in writing to the investigator before 
commencement of this study.   
 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  This consent 
form will be submitted with the protocol for review and approval by the IRB for the study.  The formal 
consent of a subject, using the IRB-approved consent form, must be obtained before that subject 
undergoes any study procedure.  The consent form must be signed by the legally acceptable guardian 
and the principal investigator. 
11 Study Finances 
11.1 Funding Source 
This study will be funded through the Duchossois Family Institute Multidisciplinary Grant; the Comer 
Development Board; and through a generous donation by Paul and Mary Yovovich. 
11.2 Conflict of Interest 
All University of Chicago investigators will follow the applicable University conflict of interest policy(ies). 
11.3 Subject Stipends or Payments 
Subjects will not receive reimbursement for their participation in this trial other than vouchers to pay for 
parking at the University. 
12 Publication Plan 
The results of this study will be reported in manuscripts by the co-investigators and submitted to relevant 
journals. 

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13 References 
1. 
Gupta RS, Warren CM, Smith BM, et al. The Public Health Impact of Parent-Reported Childhood 
Food Allergies in the United States. Pediatrics 2018;142. 
2. 
Primeau MN, Kagan R, Joseph L, et al. The psychological burden of peanut allergy as perceived 
by adults with peanut allergy and the parents of peanut-allergic children. Clin Exp Allergy 2000;30:1135-
43. 
3. 
Lieberman JA, Gupta RS, Knibb RC, et al. The global burden of illness of peanut allergy: A 
comprehensive literature review. Allergy 2020. 
4. 
Vickery BP, Vereda A, Casale TB, et al. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J 
Med 2018;379:1991-2001. 
5. 
Anagnostou K, Islam S, King Y, et al. Assessing the efficacy of oral immunotherapy for the 
desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet 
2014;383:1297-304. 
6. 
Bird JA, Spergel JM, Jones SM, et al. Efficacy and Safety of AR101 in Oral Immunotherapy for 
Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical 
Trial. J Allergy Clin Immunol Pract 2018;6:476-85.e3. 
7. 
Anagnostou K, Clark A. The management of peanut allergy. Arch Dis Child 2015;100:68-72. 
8. 
Bunyavanich S, Berin MC. Food allergy and the microbiome: Current understandings and future 
directions. J Allergy Clin Immunol 2019;144:1468-77. 
9. 
Luu M, Monning H, Visekruna A. Exploring the Molecular Mechanisms Underlying the Protective 
Effects of Microbial SCFAs on Intestinal Tolerance and Food Allergy. Front Immunol 2020;11:1225. 
10. 
Stefka AT, Feehley T, Tripathi P, et al. Commensal bacteria protect against food allergen 
sensitization. Proc Natl Acad Sci U S A 2014;111:13145-50. 
11. 
Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene 
hypothesis. Nat Rev Immunol 2001;1:69-75. 
12. 
Wesemann DR, Nagler CR. The Microbiome, Timing, and Barrier Function in the Context of 
Allergic Disease. Immunity 2016;44:728-38. 
13. 
Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature 
2011;473:174-80. 
14. 
Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. 
Nature 2012;486:207-14. 
15. 
Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, 
regulate colonic Treg cell homeostasis. Science 2013;341:569-73. 
16. 
Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty 
acids in health and disease. Adv Immunol 2014;121:91-119. 
17. 
Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the 
differentiation of colonic regulatory T cells. Nature 2013;504:446-50. 
18. 
Tan J, McKenzie C, Vuillermin PJ, et al. Dietary Fiber and Bacterial SCFA Enhance Oral 
Tolerance and Protect against Food Allergy through Diverse Cellular Pathways. Cell Rep 2016;15:2809-
24. 
19. 
Donohoe DR, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism 
and autophagy in the mammalian colon. Cell Metab 2011;13:517-26. 
20. 
Byndloss MX, Olsan EE, Rivera-Chavez F, et al. Microbiota-activated PPAR-gamma signaling 
inhibits dysbiotic Enterobacteriaceae expansion. Science 2017;357:570-5. 
21. 
Berni Canani R, Sangwan N, Stefka AT, et al. Lactobacillus rhamnosus GG-supplemented 
formula expands butyrate-producing bacterial strains in food allergic infants. ISME J 2016;10:742-50. 
22. 
Feehley T, Plunkett CH, Bao R, et al. Healthy infants harbor intestinal bacteria that protect 
against food allergy. Nat Med 2019;25:448-53. 
23. 
Schwiertz A, Hold GL, Duncan SH, et al. Anaerostipes caccae gen. nov., sp. nov., a new 
saccharolytic, acetate-utilising, butyrate-producing bacterium from human faeces. Syst Appl Microbiol 
2002;25:46-51. 
24. 
Duncan SH, Louis P, Flint HJ. Lactate-utilizing bacteria, isolated from human feces, that produce 
butyrate as a major fermentation product. Appl Environ Microbiol 2004;70:5810-7. 

Fiber in Peanut OIT 
 
Page 22 
Version: 9 
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This material is the property of the University of Chicago. 
                                             Do not disclose or use except as authorized in writing by the study PI                                05.16.2023 
25. 
Bao R, Hesser LA, He Z, Zhou X, Nadeau KC, Nagler CR. Fecal microbiome and metabolome 
differ in healthy and food-allergic twins. J Clin Invest 2021;131. 
26. 
Ze X, Duncan SH, Louis P, Flint HJ. Ruminococcus bromii is a keystone species for the 
degradation of resistant starch in the human colon. ISME J 2012;6:1535-43. 
27. 
Walker AW, Ince J, Duncan SH, et al. Dominant and diet-responsive groups of bacteria within the 
human colonic microbiota. ISME J 2011;5:220-30. 
28. 
Salonen A, Lahti L, Salojarvi J, et al. Impact of diet and individual variation on intestinal 
microbiota composition and fermentation products in obese men. ISME J 2014;8:2218-30. 
29. 
Baxter NT, Schmidt AW, Venkataraman A, Kim KS, Waldron C, Schmidt TM. Dynamics of Human 
Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable 
Fibers. mBio 2019;10. 
30. 
Karcher N, Pasolli E, Asnicar F, et al. Analysis of 1321 Eubacterium rectale genomes from 
metagenomes uncovers complex phylogeographic population structure and subspecies functional 
adaptations. Genome Biol 2020;21:138. 
31. 
Cait A, Cardenas E, Dimitriu PA, et al. Reduced genetic potential for butyrate fermentation in the 
gut microbiome of infants who develop allergic sensitization. J Allergy Clin Immunol 2019;144:1638-47 
e3. 
32. 
Brandstrom J, Vetander M, Sundqvist AC, et al. Individually dosed omalizumab facilitates peanut 
oral immunotherapy in peanut allergic adolescents. Clin Exp Allergy 2019;49:1328-41. 
33. 
Ho HE, Bunyavanich S. Microbial Adjuncts for Food Allergen Immunotherapy. Curr Allergy 
Asthma Rep 2019;19:25. 
34. 
Abdel-Gadir A, Stephen-Victor E, Gerber GK, et al. Microbiota therapy acts via a regulatory T cell 
MyD88/RORgammat pathway to suppress food allergy. Nat Med 2019;25:1164-74. 
35. 
Tang ML, Ponsonby AL, Orsini F, et al. Administration of a probiotic with peanut oral 
immunotherapy: A randomized trial. J Allergy Clin Immunol 2015;135:737-44 e8. 
36. 
Hsiao KC, Ponsonby AL, Axelrad C, Pitkin S, Tang MLK, Team PS. Long-term clinical and 
immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year 
follow-up of a randomised, double-blind, placebo-controlled trial. Lancet Child Adolesc Health 2017;1:97-
105. 
37. 
Lejk A, Myśliwiec M, Myśliwiec A. Effect of eating resistant starch on the development of 
overweight, obesity,and disorders of carbohydrate metabolism in children. Pediatr Endocrinol Diabetes 
Metab 2019;25:81-4. 
38. 
Montroy J, Berjawi R, Lalu MM, et al. The effects of resistant starches on inflammatory bowel 
disease in preclinical and clinical settings: a systematic review and meta-analysis. BMC Gastroenterol 
2020;20:372. 
39. 
Sanders LM, Dicklin MR, Palacios OM, Maki CE, Wilcox ML, Maki KC. Effects of potato resistant 
starch intake on insulin sensitivity, related metabolic markers and appetite ratings in men and women at 
risk for type 2 diabetes: a pilot cross-over randomised controlled trial. J Hum Nutr Diet 2021;34:94-105.