A Pilot Trial of Dietary Therapy Directed by the Esophageal Sponge in the Management of Eosinophilic Esophagitis.
Phase: NA
Conditions: Eosinophilic Esophagitis
Sponsor: Mayo Clinic

 
 
A Pilot Trial of Dietary Therapy 
directed by the Esophageal 
Sponge in the Management of 
Eosinophilic Esophagitis 
 
NCT02599558 
 
11/5/2019 

Version # 14 - Date 11/05/2019 
A Pilot Trial of Dietary Therapy directed by the Esophageal 
Sponge in the Management of Eosinophilic Esophagitis 
 
 
 
 
Principal Investigator: Jeffrey A. Alexander, M.D., F.A.C.P.  
 
 
Coinvestigators: 
, 
 
 
Study Coordinators: 
 
 
  
 

 
 
Background 
 
Dietary Therapy has been shown to be [1] successful in the treatment of adult and pediatric 
patients with eosinophilic esophagitis [2-5]Dietary studies were initially reported in children, but 
the results appear to be similar in adult patients.  Elemental diets are successful in 70-95% of 
patients but are poorly tolerated [1, 2]. A six food elimination diet has been effective in about 
70% of adult patients with EoE [3, 4]. In these adult studies skin prick testing was not helpful in 
predicting which foods would lead to a flare of disease when reintroduced into the diet. 
Therefore, the current standard of care requires multiple EGDs with esophageal biopsy during 
the dietary restriction and reintroduction phases of this study. Since we are making lifelong 
dietary decisions during this process of food reintroduction, it is imperative we be accurate. 
Unfortunately, these multiple EGDs have significant cost and are invasive procedures with some 
risk. Moreover, there is significant indirect costs with travel and time off work for the patients 
and drivers. 
 
Recently, Katzka et al have found the esophageal sponge to be an accurate technique of 
accessing esophageal eosinophilia in EoE [6]. The sponge is swallowed as a 12 mm capsule on a 
string. The capsule rapidly dissolves upon entering the stomach and the sponge then expands and 
can be pulled out the mouth five minutes after ingestion. In this study, the procedure was very 
well tolerated and all patients preferred the sponge to endoscopy.In the event this cytosponge is 
unavailable we will use the CapNostics EsophaCap, which is very similar to the cytosponge and 
is FDA approved, in order for the subjects to complete the trial.Therefore the sponge is a well 
tolerated, inexpensive, very low risk procedure that would be an ideal option to replace EGD 
esophageal sampling in the evaluation of dietary treatment of EoE.  
 

We perform a pilot study using the esophageal sponge to direct dietary therapy in adult patients 
with EoE.  
Hypothesis: 
Esophageal sampling with the esophageal sponge can accurately direct dietary 
therapy in EoE. 
 
Aims 
1.  Evaluate the effectiveness of the esophageal sponge to guide dietary therapy in 
adult patients with EoE. 
 
Methods 
 
Design: Prospective trial 
 
Inclusion Criteria: 
➢ 18 to 80 years of age 
➢ Diagnosed with Eosinophilic Esophagitis > than 15 Eos phf  
➢ Going through the six food elimination diet or have just completed 
elimination the six foods: fish, nuts, eggs, soy, wheat, and milk  
Patients that have completed the six food elimination diet clinically and none of the foods 
were identified as being the food causing their EoEExclusion Criteria: 
➢ Clinical evidence of infectious process potentially contributing to dysphagia 
(e.g. candidiasis, CMV, herpes) 
➢ Other cause of dysphagia identified at endoscopy (e.g. reflux esophagitis, 
stricture, web, ring, achalasia, esophageal neoplasm) 
➢ Esophageal minimal diameter < 13 mm on structured barium esophagram 
 
 

Timeline: 
Entry 
• Patients will be recruited from the Esophageal Clinic. 
• Meet with study investigator (JAA, DAK, KR). Vital signs and weight will be recorded; 
dysphagia (Appendix #1 ) and EEAI (Appendix #2) questionnaires will be evaluated. 
• Patients will complete the food anaphylaxis questionnaire; any food positive will be 
restricted from the diet and not reintroduced. If a patient is avoiding one of the six foods for 
any reason, we will not reintroduce this food. 
• Patients will meet with a dietician for an educational session 
 
 
Study Period  
• Patients will meet with an EoE dietician and go on the Mayo six food elimination diet (SFED)  
avoiding: fish, nuts, eggs, soy, wheat, and milk 
• 
Study flow diagram Appendix #4 
• 
Non responders to the SFED will be placed on the extended SFED avoiding the following: 
corn and legumes. 
• 
Patients will undergo a repeat EGD with biopsies after dietary reintroduction is complete for 
histologic assessment. 
• 
At the end of the dietary reintroduction patient will evaluate tolerance of the sponge and 
endoscopy by a standardized Lickert scale (Take from the Katzka study) 
• 
Patients will complete a 3 day dietary log during the first 2 weeks of SFED. This will be 
reviewed by the dieticians and if noncompliant a dietician will talk to the patient and the diet 
will be extended 3 more weeks.  
. Significant dietary compliance issues or dietary questions will lead to direct conversation 
with a research dietician and the investigators continuation of the same treatment until 
dietary compliance is obtained. Inability to maintain reasonable dietary compliance will lead 
to study withdrawal. 
 

Post Therapy Period 
• Patients will return for follow up at 6 months 
• Sponge and EGD with biopsy  will be performed if recurrent dysphagia develops as defined 
above (The EGD/biopsies will be part of the clinical care) 
• If symptoms have not reoccured a sponge will be completed at the 6 months’ visit 
 
Time line (Appendix #4) 
Methods: 
Six esophageal biopsies will be obtained from the entire esophagus at EGD.  Histology 
containing a peak level of  < 15 eosin / hpf on all biopsy specimens will be considered histologic 
remission. All biopsy specimens will be read by the same study investigator (TS). All EGD are 
clinically indicated in this protocol and will be performed in the clinical arena with clinical 
charges.  
On sponge cytology remission will be defined as having no fragments of tissue containing < 15 
eosin/hpf. All sponge studies will be read by the same study investigator (TS). 
 
Analysis 
 
Sample Size 
100 patients. 
 
Definitions of symptomatic remission: 
• 
Symptoms: A complete response will be defined by 
o EEsAI PRO score of < 20 
 
 

Primary Analysis 
We will determine 1) what % of patients are in  histologic remission at the end the end of dietary 
therapy, 2) what % of those are in symptomatic remission as determined by EEAI  PRO  score.  
 
Compare these histologic results to  Mayo controls  
Secondary Analyses 
Compare cost of standard approach to sponge approach using last 20 standard patients 
Compare final sponge result to EGD histology. 
Compare patient tolerance of sponge  to endoscopy. 
 
Analysis of Safety 
The sponge has been found to be very well tolerated in a previous study[6]. Any symptoms post 
sponge study will be evaluated by the MD investigator as clinically indicated. All sponge studies 
will be performed by the MD investigator. 
The dietician will meet with the patient at the study initiation, completion, and at any time in 
between if clinically indicated. Nutritional deficiencies are uncommon with a short term dietary 
study of EoE. After the food reintroduction phase, patients will be given dietary supplementation 
information depending on their dietary restrictions prior to the 6 month treatment period.  
We do not feel a safety board is needed for this study 
 
Feasibility / time frame 
 
We see about 150 new patients with symptomatic eosinophilia, 30% have PPI-REE and 70% 
EoE,  each year in the Esophageal Clinic. Dietary therapy is becoming increasingly more popular 
among our patient population.  Currently, we have started 20 patients on dietary treatment over 

the last year. Several patients interested in dietary therapy have been delaying initiating the 
program awaiting the clinical use of the sponge, preferring this over the cost, risk, and 
inconvenience of EGD.  We would expect to recruit 35  patients over the next two years and 
expect a dropout rate of 15%. We expect to complete the study within 24 months time. 
Addendum: We would like to increase our enrollment to 100 subjects. Many patients are 
interested in the cytosponge as it eliminates several EGDs during the six food elimination diet. 
We would like to offer the sponge trial to these patients as it helps them through completing the 
diet. 
Strengths / limitations 
The strength of the study is its simplicity and very high probability of being completed in 2 
years’ time. Many patients have chosen to be in this study over the traditional endoscopically 
directed dietary care. Therefore, there will be some inherent bias in their preferences of the 
sponge related to endoscopy. 
Human Issues: 
Treatment office visits and sponge costs will be covered  by  research funds.  Standard medical 
care would be at least 5 endoscopies during the food reintroduction period, which are being 
replaced with the sponge. Upon publication, we will mail all participants a thank you note, with a 
copy of the manuscript, explaining the results in layman terminology, as a way of providing 
feedback for their participation. 
Gender / Minority Mix 
All patients meeting criteria will be offered enrollment in this study. We expect the 
gender/minority mix of the subjects to reflect that of the Rochester community adjusted for the 
increased prevalence of eosinophilic esophagitis in males. We therefore anticipate approximately 
70% male and 30% female with 85% Caucasian and 15% minority origin (Black, Hispanic and 
Asian). 
 
Budget 

The budget submitted to CURE foundation is enclosed. If this is not funded by CURE we have 
adequate funds in Dr Alexander’s research account to complete the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Study Timeline: 
Eligible patients meeting the diagnostic definition of EoE and are on or starting  the eliminated 
the six foods for the SFED diet patients will meet with one of 3 investigators (JAA, DAK, KR) 
to discuss diagnosis and treatment 
1. Meet with the study coordinator, explain study, either at the beginning of the diet or 
when patient returns after the eliminating the six foods,  consent process completed. 
2.  Patients will complete the EEsAI questionnaire to  assess symptoms 
3. Patients will complete the anaphylaxis questionnaire: any food positive will be 
restricted from the diet and will not be reintroduced. 
4. If patient meets criteria an appointment will be set up to meet with a dietitian to 
discuss the  SFED diet.  This is all part of the patients clinical care. 
5. The clinical SFED protocol will be followed as below: 
 
• Meet with a dietitian 
• Patients will follow the SFED by excluding milk, wheat, eggs, soy, nuts, and 
fish for 6 weeks 
• Return for an upper endoscopy/biospsies (all part of their clinical care) 
Patients with symptomatic and histologic response (defined by <15 eos per HPF EGD/biospsies) 
will be defined as responders. Responders will then undergo food reintroduction via the 
following protocol: 
a. Fish  for up to 12 weeks 
b. Return for cytosponge to monitor the patients eosinophilia 
histologically. 
c. At any time if the histology is positive > 15 eosinphils phf we will wait 
6 weeks prior to adding in a new food.   If negative <15 eosinophils phf 
we will add in the next food. 
d. Nuts for up to 12 weeks 
e. Repeat cytosponge  
f. Eggs for up to 12 weeks 
g. Repeat cytosponge 
h. Soy for up to 12 weeks 
i.  Repeat cytosponge 
j. Wheat for up to 12 weeks 
k. Repeat cytosponge 
l. Milk for up to 12 weeks 

m. Repeat cytosponge 
n. If pathology shows ≥ 15 eos per HPF, eliminate milk and repeat 
cytosponge 
When all foods added back, EGD and cytosponge at the end of the diet (EGD is part of the 
clinical care. 
Follow up with the cytosponge/ histology in 6 months  
We are further extending the in intervals returning for the cytosponge, scheduling is an issue.  
Also for patients that are having symptoms but had a negative cytosponge results we will 
continue them on the same foods and have them return in  two weeks for a repeat cytosponge. 
We are also finding that some patients are not responding to a food group, so we would like to 
further extend each re-introduction to up to 12 weeks. 
SFED nonresponders with symptomatic and histologic nonresponse (defined by >15 eos per HPF 
on cytosponge) will then undergo an expanded directed 8 food elimination diet including the six 
foods adding corn and legumes.  After 8 weeks on this diet patients will return to repeat the 
cytosponge/ histology. If patients are still nonresponders this will be the end of the study for 
them.  Reponders will undergo the food reintroduction following the same protocol as the 
reponders for the six food diet only excluding the additional foods corn and legumes.  
When all foods added back, EGD and cytosponge at the end of the diet 
Follow up with the cytosponge/ histology in 6 months  
 
Patients that have completed the six food elimination diet clinically and no foods were identified 
as the food causing their swallowing issues, we will offer participation in the cytosponge trial. 
We will add foods back in up to 12 week intervals to see if the additional time between foods 
will help identiy the food they are reacting to. 
 
Addendum: 
 We will senda limited data set with  sample  a portion of the primary cytosponge will be flash frozen in 
a dry eppie tube and  shipped on dry ice.,  for extra-cellular RNA signature analysis with possible 
detection of EoE specific lumen protein products proposed to Dr. 
 lab at the Cincinnati 
Children’s Hospital 
 
 

 
Addendum (11/05/2019): 
Revise inclusion criteria of “>/ 15eos/hpf and failed to respond to high dose PPI” to “>/ 15 eos/hpf found 
upon initial biopsy”. The general agreed consensus for diagnosing Eosinophilic Esophagitis has changed 
and PPI-responsive EoE is no longer being recognized as a separate diagnosis, rather, eosinophils found 
in the esophagus is EoE. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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