Clinical trial NCT05444543
Conditions: Eosinophilic Esophagitis
Keywords: Fluticasone Budesonide Adolescent Cycling
Sponsor: University Hospitals Cleveland Medical Center
Start date: 2021-11-17; Completion date: 2023-10-13
Enrollment: 23 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of our research study is to assess whether patients with EoE who have achieved control of their disease on topical Fluticasone or Budesonide are able to cycle or take breaks from their treatment with continued remission of their EoE. There will be 30 participants enrolled in this study. There will be 15 patients who will stay on steroid therapy every day and 15 patients who will cycle their steroid therapy on and off to help us compare the two groups. The cycling group will cycle their steroid therapy in a three-months on three-months off fashion.

Detailed description:

Arms: arm 1: Participants in this arm will continue with their normal standard of care regimen of daily topical steroids arm 2: Participants in this arm will cycle their topical steroid therapy in a three-months on three-months off fashion
Interventions: intervention 1: Fluticasone Propionate intervention 2: Budesonide
Intervention descriptions: intervention 1: Participants will cycle topical steroid in a three-months on three-months off fashion intervention 2: Participants will cycle topical steroid in a three-months on three-months off fashion

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
Effectiveness of Cycling of Topical Steroid Therapy in Maintaining Clinical and Histologic Remission in 
Eosinophilic Esophagitis 
 
NCT05444543 
 
12/12/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Objectives  
The purpose of our research study is to assess whether patients with Eosinophilic Esophagitis (EoE) who 
have achieved clinical remission on topical corticosteroids are able to electively cycle their topical 
corticosteroid treatment with sustained remission of their EoE. The primary aim is to determine the 
number of patients who will remain in remission at one year following cycling of topical steroids as 
compared to those receiving continuous topical corticosteroid treatment. Our hypothesis is that in EoE, 
cycling topical corticosteroids is effective in sustaining remission and beneficial in decreasing risks of long 
term use of these medications when compared to continuous therapy.  
Our secondary aims are:  
i. 
The percent of patients who develop adverse effects of cycled compared to continuous 
steroid therapy.  
ii. 
The level of esophageal mucosal biochemical mediators of EoE in patients on cycled 
compared to continuous steroid therapy.  
Background  
Eosinophilic Esophagitis is a food antigen driven inflammatory condition characterized by esophageal 
dysfunction. It was first identified in the 1960s though was only described as its own pathological entity 
in the 1990s. In the last two decades, knowledge about this disease has grown significantly (14). EoE 
typically presents in two age peaks, one in childhood and again in adults aged 30- 40 years. Symptoms in 
children can be broad and include vomiting or regurgitation, dysphagia, heart burn, food impaction, 
abdominal pain, feeding difficulty, and failure to thrive. Endoscopy (esophagogastroduodenoscopy, EGD) 
in patients with EoE often reveals esophageal edema, linear furrows, concentric rings, white exudates, 
esophageal narrowing and strictures. Definitive diagnosis is made histologically with >15 eosinophils per 
HPF seen on esophageal biopsy obtained via EGD. Treatment options for induction or remission includes 
high dose PPIs (50-60%effective), topical steroids (50-90% effective) and elimination diets (70% effective) 
(1). Esophageal dilation is also indicated in those with stricturing disease. Medical treatments are 
initiated for an 8-12 week course with follow up endoscopy preformed thereafter, for assessment of 
histologic remission evidenced by <1 Eos per HPF on esophageal biopsies (1). 
EoE is now known to be a chronic disease, and if left untreated, can progress from mucosal inflammation 
to mucosal fibrosis and narrowing, thus causing esophageal strictures. Many studies have shown 
evidence that despite achieving symptomatic, endoscopic and even histologic remission, all aspects of 
disease have potential to recur after long term discontinuation of therapy (5,6,7,11). One such study by 
Liacouros et al. showed that in children with histologic remission after treatment with 4 weeks of either 
oral or topical steroids, mean eosinophil count had returned to pre-treatment levels on subsequent 
biopsies 6 months after treatment cessation (11). Due to this, it is suggested that maintenance therapy 
be initiated. However, to date there is little consensus as to what defines effective maintenance therapy 
for EoE, which is instead regarded as a “preference sensitive matter” (1). In our institution at Rainbow 
Babies and Children’s Hospital topical steroids, specifically swallowed viscous budesonide or swallowed 
fluticasone via metered dose inhaler, are often used successfully in the treatment of EoE. However, when 
used longer than a three month duration, topical steroids have been shown to increase the risk of 
candida esophagitis, oral thrush, and adrenal insufficiency (12). Further, compliance and quality of life on 
long medications continues to be an ongoing concern. Due to this, it can be beneficial to cycle steroid 


responsive patients off of medications during times of histologic and symptomatic remission. This study 
aims to identify whether our current practice of topical corticosteroid treatment in a 3 month on and 3 
month off cycle is successful in maintaining symptomatic and histological remission, as well as 
minimizing adverse effects of long term steroid use. 
Inclusion and Exclusion Criteria  
Patients will be screened through chart review to see if they meet inclusion criteria as described below. 
 
Number of Research Participants  
This is a single center prospective study taking place at Rainbow Babies and Children’s Hospital consisting 
of a total of 30 patients. We will enroll 15 subjects to be in the intervention group to electively cycle 
topical Budesonide or Fluticasone 3 months on and 3 months off for treatment of EoE. 15 Patients will be 
in the control group for a total of 30 patients in the study. 
Recruitment Methods  
All subjects who are eligible for either the intervention group or the control group will be identified 
through our medical records of active EoE patients seen by Rainbow Babies and Children’s Hospital 
Department of Pediatric Gastroenterology, Hepatology and Nutrition who are on topical Fluticasone or 
Budesonide treatment. Their medical charts will be individually reviewed by the PI to determine if they 
meet inclusion criteria as noted above. 
Once the patients are identified, the primary GI physician for each of the patients will be contacted by 
the PI to obtain permission to approach his or her patient for recruitment to the study. This will be done 
via HIPAA protected email or discussed at weekly departmental meeting. Written or verbal permission 
will be obtained by the PI to approach each individual patient for consent and documented in the 
research records. Once permission from the primary GI has been obtained, the patients will be recruited 
to participate in the study. 


Patients may be recruited either in person or virtually. For the in person consent process, patients and 
families will be approached by the PI or other qualified study personnel at a scheduled clinic visit or 
during inpatient hospitalizations. They will be asked to participate in the study and a copy of the Basic 
consent form as well as assent form will provided to the patient and family. These forms will be 
distributed to all participating outpatient sites. The PI will review the research study with the patient and 
parent and answer any questions they may have. The PI will then inform patient of next steps and obtain 
agreement for further contact either in person, by phone, or email for duration of the study. A full, 
written signed informed consent and assent will be obtained from parent(s) and patients who will be 
enrolled in the intervention and control group of this study. 
For virtual recruitment, patients will be initially contacted by email or letter using the interventional 
recruitment template. After 14 days of initial virtual or in person contact, the patients will be contacted 
by phone to follow up and review the study. If the parent and patient agree to be a part of the research 
study, a virtual appointment will be set up via Doxy.me for the consent process as described below. 
If the primary GI physician, the patient or the parents do not provide consent to be in the study, the 
patient will not be approached further by the PI or other study personnel. 
Setting  
1. All research activity will be conducted at Rainbow Babies and Children’s Hospital, satellite campuses, 
and affiliate hospitals (UH St. John Medical Center). Satellite campuses include the following UH 
outpatient locations: Landerbrook, Mentor, Medina, Solon, Twinsburg, Parma, Fairlawn, and Firelands.  
2. Research team will identify and recruit potential research participants in person at Rainbow Babies 
and Children’s Hospital, UH St. John Medical Center, and UH outpatient clinics. Patients may also be 
recruited virtually through a video conferencing tool.  
3. Lab work will be obtained at Rainbow Babies and Children’s Hospital, UH St. John Medical Center, UH 
outpatient locations  
4. Chart review and data collection will be performed within the Division of Gastroenterology, 
Hepatology & Nutrition at Rainbow Babies and Children’s Hospital 
Consent Process  
Patients who meet inclusion criteria will be identified and recruited for involvement in this study during 
their outpatient endoscopy or outpatient clinic visits. Patients may also be contacted by email or letter 
and subsequently by phone for the consent process. 
For the in person consent process, patients and families will be approached by the PI or other qualified 
study personnel to participate in the research study. The PI will review the research study with the 
patient and parents and answer any questions they may have. They will be given a copy of the Basic 
consent form, as well as assent form if indicated. If willing to participate, [the patient and parents/legal 
guardians will sign the informed consent. Then] the patient and family may choose whether they would 
like to being cycling their steroid therapy or continue on their continuous treatment plan, thereby 
choosing in which arm of the study they would like to participate. The PI will then inform patient of next 
steps and obtain agreement for further contact either in person, by phone, or email for duration of the 


study. A full, written signed informed consent and assent will be obtained from parent(s) and patients 
who will be enrolled in the intervention and control group of this study. 
For the virtual consent process, patients and families will be initially contacted by email or letter. After 14 
days, the patients will be contacted by phone to follow up on the email or letter and review the study. If 
the parent and patient agree to be a part of the research study, another virtual appointment will be set 
up via Doxy.me for the consent process. The consent form will be sent to the patient prior to the 
appointment via email. During the virtual appointment, the parents will verify identity by showing an 
identification card. The patient’s identity will be verified by the parent. If the bandwidth or connection 
does not permit a virtual visit with audiovisual capabilities, the potential participant can take a picture of 
their face and a picture of their photo ID and email both of these photographs to the study team’s 
University Hospitals email address to verify identity. If the adult is a legal guardian and not the parent, a 
photo of the legal documentation will also be requested and emailed to the PI. The child will sign the 
assent form if age 7- 13 and on the consent form if age 14 and older. Once identity has been verified, the 
full informed consent process will take place during the virtual visit. If the participant decides to enroll, 
an electronic signature can be obtained from the REDCap e-consent link during the virtual visit. If the 
potential participant is unable to utilize the electronic format signature, he/she can print off a paper 
copy, sign the paper during the virtual visit, and take a picture of the signature page. The picture can be 
sent to the study team’s UH email address at the end of the virtual visit. 
Sharing of Results with Research Participants 
Results of the study will be shared with the study participant as well as the subject’s primary GI physician 
and will be given via phone call or letter. The information to be shared with the primary GI physician and 
patient includes routine biopsy results from all endoscopies preformed for the study, biopsies stained for 
eotaxin or IL-13, and morning cortisol levels preformed throughout the study. 
Study Design  
This will be a single center prospective study, consisting of one intervention group and one control 
group. The intervention group will consist of a total of 15 patients who are recruited to the study as 
outlined below to electively cycle topical steroid treatment in a 3 month on 3 month off fashion. The 
control group with also consist of 15 patients to be recruited as discussed below. Data will be collected 
prospectively at each designated study visit. Demographic data will be collected retrospectively. 
Study Procedures 
Recruitment: Please refer to “Recruitment Methods” section above.  
0-3 month period: For this period of the study, study procedures are the same between the two groups. 
Newly diagnosed EoE patients who consent to study participation will initiate therapy with either 
Fluticasone or Budesonide per primary GI and patient preference. Patients who are already on topical 
steroid therapy will continue on their prescribed therapy. The screening EGD (listed as EGD 1 in the study 
timeline) will occur after 3 months of steroid treatment in the newly diagnosed patients. For those 
patients who were already on continuous topical steroid therapy, the screening EGD will occur at the 
time of their next clinically indicated EGD, which was scheduled per their primary GI physician. That is to 
say, as per the inclusion criteria, those children who are known EoE patients and already on topical 
steroids at the time of recruitment are only eligible for this study if their next clinically indicated EGD is 


within 3 months of recruitment. For example, if a patient is on topical steroid therapy and has their 
yearly EGD scheduled in 2 months, they will be eligible for the study where this scheduled EGD will relate 
to the study EGD1. We will also allow patients to be enrolled in a retrospective manner, if their 
surveillance EGD was within one month of recruitment. For these patient’s EGD1 will not include extra 
biopsies or scope day cortisol levels. For both new and known EoE patients who have enrolled in the 
study, this screening EGD (EGD 1) must show documented endoscopic remission in order to proceed 
further in the study. If the patient is not in endoscopic remission at EGD1 they will be considered a 
“treatment failure” and removed from the study. 
Control group medications and endoscopies- months 3-12: Patients who consent to participate in the 
study and chose to remain on continuous steroid therapy will be in the control arm of the study. Patients 
in the control group will remain on topical Fluticasone or Budesonide and be followed clinically for a 
total of 12 months. They will be contacted in person at their scheduled surveillance endoscopy or via 
telephone at 3 months, 6 months, 9 months and 1 year time point. At these time points, clinical 
symptom assessments and quality of life surveys will be obtained. ). If during any of the clinical 
symptoms assessments it is noted that symptoms return, or during the surveillance endoscopy a patient 
is noted to have an endoscopic flare of their EoE, they will be taken off topical corticosteroid, exited from 
the study and regarded as “treatment failure” in the study, and work with their primary GI doctor for an 
alternative treatment plan. 
Patients in the control group will have routine biopsies obtained at their 3 month and 12 month EGDs 
and any other EGDs required per primary GI discretion as part of the management of their EoE. During 
the 3 month and 12 month EGDs, we will also obtain 2 extra biopsies to stain for IL-13 and eotaxin, 
biomarkers which are thought to be involved in recruitment of eosinophils from the blood stream into 
tissue. They will also have blood work drawn for morning cortisol levels to be obtained at 3 month and 
12 month EGDs for screening of adrenal insufficiency. Blood volume will be limited to 0.8mL per blood 
draw. 
Intervention group medication cycling and Endoscopies- 3-12 month period: After documented 
endoscopic remission on topical steroids at EGD1, patients will begin their first off cycle of their topical 
corticosteroid treatment. Patients will continue to be cycled off of the topical steroid medication for a 3 
month duration (months 3-6 of this study). If at any point symptoms return during the off cycle time 
period, the patient will be restarted on the topical corticosteroid, exited from the study and regarded as 
“treatment failure” in the study. If patients remain in clinical remission after three months of medication 
free cycle, they will undergo surveillance EGD (defined as EGD 2 under Study Timeline). If during the 
surveillance endoscopy a patient is noted to have an endoscopic flare of their EoE they will be restarted 
on the topical corticosteroid, exited from the study and regarded as “treatment failure” in the study. If 
patients are noted to still be in endoscopic remission at EGD2, they are considered responsive to 
medication cycling. Patients will subsequently be restarted on topical corticosteroid for months 6-9 of 
this study followed by another medication free cycle from months 9-12. 
Clinical symptoms and QOL assessments will be completed between each three month cycle either in 
person at scheduled EGDs or via telephone or virtual visit. After completing two rounds of on/off 
medication cycling, patients will undergo a final surveillance Endoscopy at month 12 (EGD3 on study 
timeline). In a one year period, each patient in the intervention group will undergo 3 endoscopies; 3 
months after treatment initiation, 3 months after treatment cessation or “off cycling”, and 12 months 


after treatment initiation. During all EGDs, we will also obtain 2 extra biopsies to stain for IL-13 and 
eotaxin, biomarkers which are thought to be involved in recruitment of eosinophils from the blood 
stream into tissue 
All the endoscopies to be performed during the study are standard of care in our division. In our group, it 
is protocol to perform an EGD to re-evaluate remission 3 months after any new change in treatment. 
Specifically, with every new treatment, EoE patients must undergo a surveillance endoscopy 3 months 
after initiation of this new treatment. For example, 3 months after initiating treatments such as topical 
steroids, PPI, or food elimination patients will undergo EGD to evaluate appropriate response to this 
treatment. Should the patient be found responsive, no further EGD is necessary until 1 year unless 
symptoms arise. Should the patient be found unresponsive to treatment, a change in treatment will be 
instated and the patient will once again undergo EGD in 3 months to evaluate for appropriate response. 
Thus, when applied to patients who cycle steroids, they are first started on topical steroids followed by a 
surveillance EGD at 3 months. Should they be in remission they are then allowed to cycle off of their 
topical steroids for 3 months. They undergo another surveillance EGD 3 months after cycling off steroids 
in order to evaluate for sustained remission. Should EGD reveal sustained remission of their EoE they are 
deemed responsive to cycling in a 3 month on 3 month off fashion, and are allowed to continue this 
method without further surveillance EGDs until 1 year from treatment initiation unless symptoms arise. 
Outpatient visits and symptom monitoring: All patients will continue to have outpatient clinic visits with 
their primary GI physician in the year during which the study is ongoing. The number of medical visits 
will be at the discretion of the patients’ primary gastroenterologist. They will also have routine EGDs as 
stated above. QOL and clinical assessment evaluations will be given at 3 month intervals during the 
study, either in person at surveillance endoscopies or via virtual visit. 
Endoscopic biopsies and blood work: During the surveillance endoscopies, biopsies will be obtained. 6 
standard biopsies will be obtained, four in the distal esophagus and two in the mid esophagus as 
indicated by the AGA for diagnosis of EoE. We will also obtain 2 extra biopsies to stain for IL-13 and 
eotaxin, biomarkers which are thought to be involved in recruitment of eosinophils from the blood 
stream into tissue. Blood work for early morning cortisol levels will also be obtained at each surveillance 
endoscopy for evaluation of medication side effects such as adrenal insufficiency. Blood volume will be 
limited to 0.8mL per blood draw, which will occur 3 times in the intervention group and 2 times in the 
control group during the year-long study. Blood draws will occur with IV placement during scheduled 
endoscopies to limit the need for multiple needle sticks and minimize patient discomfort. Should cortisol 
levels result <10mcg/dL they will be referred to a pediatric Endocrinologist for further evaluation of 
adrenal insufficiency.  
Study Timeline  
For all patients enrolled at diagnosis, study enrollment will last 12 months from the time of initiation of 
topical steroid treatment. For known EoE patients enrolled after already having been initiated on topical 
steroid treatment at the time of recruitment, study enrollment will last 9-12 months depending on the 
time from enrollment to their scheduled EGD1. 


 
 
 
Data to be Collected for your study 
(AFTER consent and HIPAA Authorization have been obtained)  
Data will be collected prospectively, with the exception of demographic data which will be collected 
retrospectively. Data to be collected includes standard biopsies taken during EGDs as well as one 
additional biopsy set to be processed for eotaxin and IL-13. Morning serum cortisol levels will also be 
drawn two or three times during the line placements during EGDs. 
Data Analysis Plan  
The Division of Pediatric Gastroenterology, Hepatology & Nutrition cares for over 350 patients with EoE. 
Though this is a pilot study, we did perform a sample size calculation for a non-inferiority (equivalence) 
study using values based upon our clinical experience and published literature (75% remission in control; 
70% remission in test; 65% non-inferiority limit). If there is a difference of the continuous therapy of 5% 
(70% vs 65%), a sample size of 10 per group will be required to be 90% sure that the upper limit of a 


onesided 95% confidence interval will exclude a difference in favor of the control of more than 65%. Our 
goal for recruitment is 15 patients per group to account for patient dropout.  
Demographic characteristics will be summarized using standard descriptive summaries such as means 
and standard deviations for continuous variables and percentages for categorical variables. The primary 
endpoint summarized using percentages. The secondary endpoint will be summarized using percentages 
and means and standard deviations and compared using parametric and non-parametric tests. 
Confidentiality  
Multiple measures will be undertaken to adhere to patient confidentiality. Data collection will be limited 
to the amount necessary to achieve the aims of this research. All communication regarding research 
activities including obtaining consent and reviewing study procedures will be conducted in a private 
room or location. Data will be coded to remove direct identifiers and stored electronically in a password 
protected server and password protected documents. 
Risks to Research Participants  
Risks pertaining to the intervention group includes recurrence of EoE symptoms during cycling topical 
corticosteroids. Should this occur patients will be re-started on topical corticosteroids at the time of 
symptom recurrence and be considered failure of treatment in investigational arm of the study. There is 
also increased risk to the intervention group as compared to the control group associated with an 
increase in the number of endoscopic evaluations they will undergo. Patients in both arms of the study 
will undergo a surveillance endoscopy 3 months after initiation of steroids and one year after initiation of 
treatment. However, patients in the intervention group will also undergo an additional surveillance 
endoscopy at about 6 months from treatment initiation correlating with the end of their first “off 
medication” cycle. The additional EGD is standard of care for all of our patients who are cycling steroids 
and is preformed regardless of research study participation. 
The risks secondary to EGD will be monitored closely and treated as part of standard of care at our 
center. In addition, I will have a Data Safety Monitoring Committee (DSMC) to serve as an Independent 
Safety Monitor (ISM) and monitor any adverse events. Adverse events will be reported to the IRB as well 
as to the ISM and the patient’s primary GI physician. The ISM will receive notification of an adverse event 
through a written report that will be sent via HIPAA protected email from the primary investigator. 
Risks that pertain to both the intervention group and the control group includes the risk of the two extra 
biopsies taken during surveillance endoscopies. This includes increased risk of bleeding and perforation. 
The extra biopsies should not add more than 30 seconds of time to the procedure and thus risk from 
increased time under anesthesia is minimal. Both groups also have the potential risk of emotional 
discomfort due to answering questionnaires throughout the year, occurring at 3 months, 6 months, 9 
months and 1 year. 
Provisions to Protect the Privacy Interests of Research Participants 
To minimize the risk of breach of confidentiality, we will not use the subject’s name or medical record 
number to identify them on any study records. Instead, a unique study number will be assigned to each 
subject. Only this number will be used on study documents that relate to the subject. The list containing 
subject names, medical record number and corresponding unique study number will be kept 


electronically on a password protected server and password protected document. In addition, patients 
will be taken to a private area when obtaining consent and discussing study procedures. 
Potential Benefit to Research Participants 
Subjects who consent to the intervention arm of the study may have direct benefit of decreasing the 
amount of days a year in which they must take daily medications and thus decrease potential for side 
effects from these medications, however these benefits may vary and are not guaranteed. There will not 
be a direct benefit to subjects who will be in the control group. The results of this study may potentially 
benefit other patients with EoE as it would provide more flexibility for treatment duration and lower 
risks of long term steroid use. 
Withdrawal of Research Participants 
Subjects may withdraw from the investigational arm of the study at any time without affecting their care. 
They may also be discontinued from the study at the discretion of the primary investigator due to failure 
to comply to cycling times, loss to follow-up, failure to respond clinically to topical steroids, recurrence of 
symptoms during an off steroid cycle, or if they experience an adverse drug effect. It will be documented 
whether or not each subject completes the investigational arm of the study and if/why steroid cycling is 
discontinued. Subjects will be notified in writing if they are withdrawn from the investigational arm of 
the study. 
Alternatives to Participation 
The alternative is to not participate in the investigational arm of this study or in the control group. If 
patients do not want to participate in the study, they will continue with their current treatment plan with 
topical Budesonide or Fluticasone. If patients do not want to participate in the study but have an interest 
in cycling their topical steroid treatment, this can be discussed with their primary GI physician. Currently 
there is no evidence based guidelines for elective cycling of steroids in standard practice, but this can be 
done on an individual basis by physicians based on their previous experiences. 
Costs to Research Participants 
There will not be any additional costs to research participants. Their outpatient medical visits and basic 
laboratory work will be within the standard of care for treatment of EoE at our center. The additional 
EGD in the intervention group will be covered by the patient’s insurance as this “extra” EGD is standard 
of care for any patient wishing to cycle off of topical steroid medication. The costs of extra biopsies and 
morning cortisol levels will be covered by FRAP grant awards, and will be processed at research 
laboratories at Case Western University for cost minimization. 
Research Participant Compensation 
Subjects in the intervention or control group of the research study will be given a $25 gift card for each 
QOL/clinical assessment questionnaire that is completed with maximum of $100. The gift cards will be 
paid within 4 weeks of completion of the study by mail to their home address that is provided in the 
electronic medical record. If the patient withdraws from the study, they will be paid for the portions that 
they completed. Participants will not be reimbursed for transportation expenses, or parking to get EGD 
or bloodwork done. 


Provisions to Monitor the Data to Ensure the Safety of Research Participants 
Data will be monitored for completeness, accuracy and adherence to protocol on a bimonthly basis by 
the primary investigator and/or research team. In addition, patients’ clinical symptoms will be assessed 
every 90 days by the PI either by phone or in-person to ensure there are no serious adverse side effects 
of topical corticosteroids as well as no increase rate in disease recurrence in the intervention arm. The 
clinical symptoms will be assessed by administration of the dysphagia symptom questionnaire (DSQ) 
assessment. The QOL questionnaires will also evaluate for problems related to mental health. Should 
these questionnaires reveal that patients are sad or upset, the PI (who is pediatric board certified and 
with clinical experience and expertise assessing for depression and suicide risk) will subsequently 
preform a PHQ-9 assessment. If the assessment is positive the PI will then evaluate for active suicidal 
ideation with a plan or intent as needed. If assessment is negative, the PI will refer either to the 
participant’s own mental health provider if he/she has one, or to community resources as listed in the 
supplemental material. If the assessment is positive for suicide risk, Frontline Cuyahoga County 216-623-
6888 or 911 will be contacted on behalf of the participant. Should these patients be found to have 
depressive symptoms related directly to participation in the study, patients will be withdrawn from 
further participation. All questionnaires will be reviewed in real time during the in person or virtual visits 
with the PI every 3 months. There will be a designated DSMC who will review the adverse effects with 
the PI every 3 months. Additionally, research data will be reviewed at the 6 month mark and if greater 
than 50% of patients have discontinued topical corticosteroid cycling, the study will be discontinued. 
Drugs or Devices 
Swallowed Fluticasone propionate using a metered dose inhaler without a space and swallowed oral 
viscous Budesonide are topical steroid medications that are FDA approved for treatment of Eosinophilic 
Esophagitis. Will attach the drug insert to this application for further information. 
References  
1. Hirano I, Chan ES, Rank MA, Sharaf RN, Stollman NH, Stukus DR, Wang K, Greenhawt M, Falck-
Ytter YT; AGA Institute Clinical Guidelines Committee; Joint Task Force on AllergyImmunology 
Practice Parameters. AGA Institute and the Joint Task Force on AllergyImmunology Practice 
Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. 
Gastroenterology. 2020 May;158(6):1776-1786. doi: 10.1053/j.gastro.2020.02.038. PMID: 
32359562. 
2. Philpott H, Dellon ES. The role of maintenance therapy in eosinophilic esophagitis: who, why, and 
how? J Gastroenterol. 2018 Feb;53(2):165-171. doi: 10.1007/s00535-017-1397-z. Epub 2017 Oct 
10. PMID: 29018965; PMCID: PMC5794528. 
3. Gómez-Aldana A, Jaramillo-Santos M, Delgado A, Jaramillo C, Lúquez-Mindiola A. Eosinophilic 
esophagitis: Current concepts in diagnosis and treatment. World J Gastroenterol. 2019 Aug 
28;25(32):4598-4613. doi: 10.3748/wjg.v25.i32.4598. PMID: 31528089; PMCID: PMC6718043. 
4. Dellon ES, Katzka DA, Collins MH, Hamdani M, Gupta SK, Hirano I; MP-101-06 Investigators. 
Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters 
Compared With Placebo in Patients With Eosinophilic Esophagitis. Gastroenterology. 2017 
Mar;152(4):776-786.e5. doi: 10.1053/j.gastro.2016.11.021. Epub 2016 Nov 23. PMID: 27889574. 
5. Straumann A, Conus S, Degen L, Frei C, Bussmann C, Beglinger C, Schoepfer A, Simon HU. Long-
term budesonide maintenance treatment is partially effective for patients with eosinophilic 


esophagitis. Clin Gastroenterol Hepatol. 2011 May;9(5):400-9.e1. doi: 
10.1016/j.cgh.2011.01.017. Epub 2011 Jan 28. PMID: 21277394. 
6. Miehlke S, Hruz P, Vieth M, Bussmann C, von Arnim U, Bajbouj M, Schlag C, Madisch A, Fibbe C, 
Wittenburg H, Allescher HD, Reinshagen M, Schubert S, Tack J, Müller M, Krummenerl P, Arts J, 
Mueller R, Dilger K, Greinwald R, Straumann A. A randomised, double-blind trial comparing 
budesonide formulations and dosages for short-term treatment of eosinophilic oesophagitis. 
Gut. 2016 Mar;65(3):390-9. doi: 10.1136/gutjnl2014-308815. Epub 2015 Mar 19. PMID: 
25792708; PMCID: PMC4789829. 
7. Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot 
C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose 
reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. 
Gastroenterology. 2014 Aug;147(2):324-33.e5. doi: 10.1053/j.gastro.2014.04.019. Epub 2014 
Apr 22. PMID: 24768678; PMCID: PMC4107112. 
8. Dellon ES, Woosley JT, Arrington A, McGee SJ, Covington J, Moist SE, Gebhart JH, Tylicki AE, 
Shoyoye SO, Martin CF, Galanko JA, Baron JA, Shaheen NJ. Efficacy of Budesonide vs Fluticasone 
for Initial Treatment of Eosinophilic Esophagitis in a Randomized Controlled Trial. 
Gastroenterology. 2019 Jul;157(1):65-73.e5. doi: 10.1053/j.gastro.2019.03.014. Epub 2019 Mar 
11. PMID: 30872104; PMCID: PMC6581596. 
9. Schaefer ET, Fitzgerald JF, Molleston JP, Croffie JM, Pfefferkorn MD, Corkins MR, Lim JD, Steiner 
SJ, Gupta SK. Comparison of oral prednisone and topical fluticasone in the treatment of 
eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008 
Feb;6(2):165-73. doi: 10.1016/j.cgh.2007.11.008. PMID: 18237866. 
10. Rajan J, Newbury RO, Anilkumar A, Dohil R, Broide DH, Aceves SS. Long-term assessment of 
esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical 
corticosteroids. J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 
10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30. PMID: 26233926; PMCID: PMC4715736.  
11. Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown-
Whitehorn T, Mamula P, Markowitz JE. Eosinophilic esophagitis: a 10-year experience in 381 
children. Clin Gastroenterol Hepatol. 2005 Dec;3(12):1198-206. doi: 10.1016/s1542- 
3565(05)00885-2. PMID: 16361045. 
12. Bose P, Kumar S, Nebesio TD, Li C, Hon EC, Atkins D, Furuta GT, Gupta SK. Adrenal Insufficiency in 
Children With Eosinophilic Esophagitis Treated With Topical Corticosteroids. J Pediatr 
Gastroenterol Nutr. 2020 Mar;70(3):324-329. doi: 10.1097/MPG.0000000000002537. PMID: 
31688699. 
13. Laserna-Mendieta EJ, Casabona S, Savarino E, Perelló A, Pérez-Martínez I, Guagnozzi D, Barrio J, 
Guardiola A, Asensio T, de la Riva S, Ruiz-Ponce M, Rodríguez-Oballe JA, Santander C, Arias Á, 
Lucendo AJ; EUREOS EoE CONNECT research group. Efficacy of Therapy for Eosinophilic 
Esophagitis in Real-World Practice. Clin Gastroenterol Hepatol. 2020 Dec;18(13):2903-2911.e4. 
doi: 10.1016/j.cgh.2020.01.024. Epub 2020 Jan 25. PMID: 31988045. 
14. Shaheen NJ, Mukkada V, Eichinger CS, Schofield H, Todorova L, Falk GW. Natural history of 
eosinophilic esophagitis: a systematic review of epidemiology and disease course. Dis 
Esophagus. 2018 Aug 1;31(8):doy015. doi: 10.1093/dote/doy015. PMID: 29617744; PMCID: 
PMC6102800. 


15. Dellon ES, Irani AM, Hill MR, Hirano I. Development and field testing of a novel patientreported 
outcome measure of dysphagia in patients with eosinophilic esophagitis. Aliment Pharmacol 
Ther. 2013 Sep;38(6):634-42. doi: 10.1111/apt.12413. Epub 2013 Jul 9. PMID: 23837796.