A Food Additive Removal Diet for Pediatric Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

— FREE  

Official title:

A Food Additive Removal Diet for Pediatric Eosinophilic Esophagitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03657771
• Other study ID #: 1173700
• Status: Completed
• Phase: N/A
• Start date: November 12, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2024
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prospective, pragmatic standard of care clinical trial comparing dietary therapies of standard dairy elimination diet alone (DED) to dairy elimination plus food additive elimination (FREE)

Description:

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. Primary symptoms manifest while eating and include dysphagia, chest pain, and food impaction. EoE was first described in the 1990s, but is increasingly recognized worldwide. It affects both adults and children.

Given that EoE is thought to be an allergen driven disease, elimination diets are considered logical and safe first-line treatment options. Elimination diets focus on the removal of the food groups most likely to evoke the inflammatory response (e.g. dairy, wheat, soy, egg, etc.). This is the first study to examine the effects of an additive free diet on eosinophilic esophagitis.

Primary Objective: To compare histologic outcomes (eosinophils per high power field: eos/hpf) of DED and FREE in children with eosinophilic esophagitis.

Secondary Objective: To compare endoscopic outcomes (Eosinophilic Esophagitis Endoscopic Reference scores: EREFs) of DED and FREE in children with eosinophilic esophagitis

Tertiary Objectives: To compare symptomatic (Pediatric Eosinophilic Esophagitis Symptom Severity Module v2.0: PEESS) and quality of life (Peds-QL EoE Module 1) outcomes of DED and FREE in children with eosinophilic esophagitis

The investigators plan to enroll 72 patients over 4 sites each enrolling 18 patients per site in a 16-month period (approximately 1 patient per month per site) having 9 patients per site in each group (DED and FREE).

The investigators will enroll patients > 5- <17 years of age with isolated esophageal eosinophilia (>15 eos/hpf). Patients with food impaction, peripheral eosinophilia > 1,500 µL , concomitant GI inflammatory conditions, history of upper GI tract surgery (e.g. fundoplication), acid reflux by pH probe, anaphylactic food allergies, severe developmental delay, taking recently prescribed inhaled corticosteroids or oral corticosteroids, have other medical conditions likely interfere with the study, has a significant psychiatric condition, has taken a PPI in the last 4 weeks, has taken swallowed steroids in the last 12 weeks, or are not fluent in spoken and written English will be excluded.

Participants will be enrolled at: Nemours Children's Hospital, Orlando, FL; Alfred I Dupont Hospital, Wilmington, DE; Seattle Children's Hospital, Seattle, WA

Once eligibility criteria are met, participants will be randomized to DED or FREE study groups. Participants will receive dietary education. Lead dietitians from each site will be identified and the approaches to dietary education will be standardized. Dietary education will be completed at the baseline visit and during follow up phone calls throughout the study.Each participant will complete all study visits in 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

1. An Institutional Review Board (IRB) approved written Parental Permission form is signed and dated by the parent or legal representative/caregiver.

2. If applicable, an Institutional Review Board (IRB) approved written Assent form is signed and dated by the participant.

3. The participant/parent(s) or legal representative(s)/caregiver(s) are considered reliable and capable of adhering to the protocol call schedule and dietary requirements.

4. The participant is >2 years to <18 years of age.

5. The participant has isolated esophageal eosinophilia (>15 eos/hpf).

6. The family has access to the internet to complete weekly surveys and to a telephone to complete weekly follow up calls.

7. The biopsy used to diagnose eosinophilic esophagitis was taken no more than 12 weeks prior to the date of enrollment.

Exclusion Criteria:

1. The participant has peripheral eosinophilia > 1,500 µL

2. The participant has concomitant GI inflammatory conditions (e.g. celiac disease, inflammatory bowel disease).

3. The participant has a history of upper GI tract surgery (e.g. fundoplication)

4. Acid reflux by pH probe is suggested (*A pH probe is not required, but may be done as standard of care)

5. The participant has severe developmental delay that, in the opinion of the investigator, could jeopardize the participant's ability to participate in the study.

6. The participant has taken prednisone in the last 12 weeks, or has taken fluticasone or budesonide in the last 8 weeks.

7. The participant has other significant medical conditions that, in the opinion of the provider, would impact the participant's ability to participate in the study.

8. The participant has a psychiatric condition that, in the opinion of the investigator, could jeopardize the participant's ability to participate in the study.

9. The participant does not speak or read English fluently.

10. The participant is currently taking a PPI (If discontinued, no washout required.)

11. The participant is currently on or previously failed a dairy free diet for EoE.

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Other:
• DED
DED: Diet eliminating dairy
• FREE
FREE: Diet eliminating dairy and food additives

Locations

Country	Name	City	State
United States	Nemours Children's Hospital	Orlando	Florida
United States	Seattle Children's Hospital	Seattle	Washington
United States	Nemours/Alfred I DuPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Nemours Children's Clinic

Country where clinical trial is conducted

United States, 

References & Publications (12)

Collins MH, Martin LJ, Alexander ES, Boyd JT, Sheridan R, He H, Pentiuk S, Putnam PE, Abonia JP, Mukkada VA, Franciosi JP, Rothenberg ME. Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. Dis Esophagus. 2017 Feb 1;30(3):1-8. doi: 10.1111/dote.12470. — View Citation

Dellon ES, Gonsalves N, Hirano I, Furuta GT, Liacouras CA, Katzka DA; American College of Gastroenterology. ACG clinical guideline: Evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol. 2013 May;108(5):679-92; quiz 693. doi: 10.1038/ajg.2013.71. Epub 2013 Apr 9. — View Citation

Dellon ES, Jensen ET, Martin CF, Shaheen NJ, Kappelman MD. Prevalence of eosinophilic esophagitis in the United States. Clin Gastroenterol Hepatol. 2014 Apr;12(4):589-96.e1. doi: 10.1016/j.cgh.2013.09.008. Epub 2013 Sep 11. — View Citation

Franciosi JP, Hommel KA, Bendo CB, King EC, Collins MH, Eby MD, Marsolo K, Abonia JP, von Tiehl KF, Putnam PE, Greenler AJ, Greenberg AB, Bryson RA, Davis CM, Olive AP, Gupta SK, Erwin EA, Klinnert MD, Spergel JM, Denham JM, Furuta GT, Rothenberg ME, Varni JW. PedsQL eosinophilic esophagitis module: feasibility, reliability, and validity. J Pediatr Gastroenterol Nutr. 2013 Jul;57(1):57-66. doi: 10.1097/MPG.0b013e31828f1fd2. — View Citation

Gonsalves N, Yang GY, Doerfler B, Ritz S, Ditto AM, Hirano I. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 2012 Jun;142(7):1451-9.e1; quiz e14-5. doi: 10.1053/j.gastro.2012.03.001. Epub 2012 Mar 3. — View Citation

Groetch M, Venter C, Skypala I, Vlieg-Boerstra B, Grimshaw K, Durban R, Cassin A, Henry M, Kliewer K, Kabbash L, Atkins D, Nowak-Wegrzyn A, Holbreich M, Chehade M; Eosinophilic Gastrointestinal Disorders Committee of the American Academy of Allergy, Asthma and Immunology. Dietary Therapy and Nutrition Management of Eosinophilic Esophagitis: A Work Group Report of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol Pract. 2017 Mar-Apr;5(2):312-324.e29. doi: 10.1016/j.jaip.2016.12.026. — View Citation

Imam T, Gupta SK. Topical glucocorticoid vs. diet therapy in eosinophilic esophagitis: the need for better treatment options. Expert Rev Clin Immunol. 2016 Aug;12(8):797-9. doi: 10.1080/1744666X.2016.1191947. Epub 2016 Jun 13. No abstract available. — View Citation

Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, Melin-Aldana H, Li BU. Effect of six-food elimination diet on clinical and histologic outcomes in eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2006 Sep;4(9):1097-102. doi: 10.1016/j.cgh.2006.05.026. Epub 2006 Jul 21. — View Citation

Kagalwalla AF, Wechsler JB, Amsden K, Schwartz S, Makhija M, Olive A, Davis CM, Manuel-Rubio M, Marcus S, Shaykin R, Sulkowski M, Johnson K, Ross JN, Riffle ME, Groetch M, Melin-Aldana H, Schady D, Palac H, Kim KA, Wershil BK, Collins MH, Chehade M. Efficacy of a 4-Food Elimination Diet for Children With Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2017 Nov;15(11):1698-1707.e7. doi: 10.1016/j.cgh.2017.05.048. Epub 2017 Jun 8. — View Citation

Martino JV, Van Limbergen J, Cahill LE. The Role of Carrageenan and Carboxymethylcellulose in the Development of Intestinal Inflammation. Front Pediatr. 2017 May 1;5:96. doi: 10.3389/fped.2017.00096. eCollection 2017. — View Citation

Newberry C, Lynch K. Can We Use Diet to Effectively Treat Esophageal Disease? A Review of the Current Literature. Curr Gastroenterol Rep. 2017 Aug;19(8):38. doi: 10.1007/s11894-017-0578-5. — View Citation

Suskind DL, Wahbeh G, Gregory N, Vendettuoli H, Christie D. Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet. J Pediatr Gastroenterol Nutr. 2014 Jan;58(1):87-91. doi: 10.1097/MPG.0000000000000103. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)	Self report measure of symptoms associated with eosinophilic esophagitis. Scores range from 0 to 100. The higher the score, the more frequent and severe the symptoms.	Baseline, 4, 8, and 12 weeks
Other	Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS): Parent Report	Parent report measure of symptoms associated with eosinophilic esophagitis. Scores range from 0 to 100. The higher the score, the more frequent and severe the symptoms.	Baseline, 4, 8, and 12 weeks
Other	Pediatric Quality of Life Inventory: Eosinophilic Esophagitis Module (PedsQL-EoE)	Self report measure of quality of life and symptoms associated with eosinophilic esophagitis. This measure has several subscales (Symptoms I, Symptoms II, Treatment, Worry, Communication, Food and Eating, Food Feelings) that produce scaled scores ranging from 0 to 100. The total scaled score also ranges from 0 to 100. A higher score indicates better quality of life.	Baseline, 4, 8, and 12 weeks
Other	Pediatric Quality of Life Inventory: Eosinophilic Esophagitis Module (PedsQL-EoE): Parent Report	Parent report measure of quality of life and symptoms associated with eosinophilic esophagitis. This measure has several subscales (Symptoms I, Symptoms II, Treatment, Worry, Communication, Food and Eating, Food Feelings) that produce scaled scores ranging from 0 to 100. The total scaled score also ranges from 0 to 100. A higher score indicates better quality of life	Baseline, 4, 8, and 12 weeks
Primary	Eosinophils Per High Power Field (eos/hpf)	Histologic change differences of maximum eosinophils per high power field	12 weeks
Secondary	Eosinophilic Esophagitis Endoscopic Reference Score (EREFS)	An endoscopic outcome measure to follow response to treatment. Scores range from 0 to 15 with higher scores indicating more endoscopic evidence of eosinophilic esophagitis.	12 weeks