Clinical trial NCT05180578: Tolerability of Goat Milk Protein in Eosinophilic Esophagitis Patients With Cow Milk Protein Trigger
Official title: Tolerability of Goat Milk Protein in Eosinophilic Esophagitis Patients With Cow Milk Protein Trigger
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Eosinophilic Esophagitis
Keywords: Eosinophilic Esophagitis
EOE
Lead sponsor: Shaare Zedek Medical Center
Sponsor class: OTHER
First posted: 2022-01-06
Enrollment: 20
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Eosinophilic esophagitis (EoE) is a chronic immune mediated disease characterized by eosinophilic infiltration in esophageal epithelium and resulting in esophageal dysfunction.

While the exact pathogenesis is yet to be elucidated, EoE is considered an atopic disease. This classification is in part due to the inflammatory infiltrate of eosinophils, basophils and T-cells producing Th2 cytokines, yet it may also be triggered by environmental allergens. In addition, the rates of atopy are approximately 3 times higher in patients with EoE than in the general population. Furthermore, and most convincing, EoE is successfully managed with dietary exclusion of triggering groups in both pediatric and adult patients, further confirming the atopic nature of the disease.

The most frequent dietary trigger for EoE is milk, but there is limited data on the cross-reactivity of milk from other species. Guidelines addressing the diagnosis and treatment of EoE in both children and adults have not addressed the use of non-bovine milk in patients with cow's milk triggered EoE.

Restrictive diets are often challenging for patients and contribute to a reduced quality of life. Our own, anecdotal experience in two patients with milk triggered EoE who requested to introduce goat's milk into the patients' diet were that reintroduction did not trigger a clinical or histological flare of EoE. These cases of successful introduction of non-bovine milk introduces the possibility that a milk-free diet need not necessarily be exclusive of all species.

The aim of this study is to assess tolerability and safety of goat's milk in patients with EoE in whom cow's milk has been confirmed to be a trigger food for their disease.

Detailed description: This prospective, multi-center trial will include patients with EoE diagnosed according to the accepted definitions: symptoms of esophageal dysfunction and \>15 Eos/HPF on an esophageal biopsy, who were confirmed to have cow's milk as a trigger by demonstrating improvement during elimination and histologic relapse following reintroduction.

Following full informed consent of the patient / guardians, patients will be offered to join the trial to assess their tolerance to goat milk.

Due to the theoretical risk of developing IgE-mediated allergy on prolonged food protein type restriction, RAST-testing or skin-prick testing to cow milk will be undertaken to exclude IgE-mediated sensitization prior to introduction of goat milk. In patients with positive results, candidates can elect to withdraw from the study or alternatively an allergist will be consulted to consider the appropriateness of a medically observed goat milk challenge.

Strict compliance with milk-free diet will be re-enforced for not less than 6 weeks prior to the patient's closest routine follow-up endoscopy. Baseline symptom profile will be recorded. Baseline endoscopy with routine biopsies (defined below) will be performed as part of the routine scheduled follow-up endoscopy as recommended by guidelines, in order to confirm histologic remission of EoE. Patients with baseline esophageal inflammation will be excluded from the study. Patients in histologic remission will be commenced on goat milk containing diet with not less than 1 daily serving.

Repeat symptom profile assessed at 6 weeks and at 12 weeks, with repeat endoscopy with routine biopsies at 12±2 weeks. If symptoms recur prior to 12 weeks, endoscopy may be moved up earlier, from 6 weeks onwards.

Patients in clinical and histologic remission at 12 weeks will be followed until week 52 with repeat scheduled endoscopy. Goat milk consumption will be permitted during the follow-up, but not be required daily as in the first time period. A goat milk consumption diary will be collected over the 4 weeks prior to this endoscopy.

Eligibility criteria: Inclusion Criteria:

* All patients diagnosed with EoE age ≤ 17.5 years at inclusion who were confirmed to have cow's milk as a trigger by demonstrating improvement during elimination and histologic relapse following reintroduction.
* Verified histologic remission on milk-free diet on endoscopy prior to intervention
* Proton-pump inhibitors may be used if treatment is maintained at the same dose from the screening endoscopy throughout the trial period, and was used at the time that milk was demonstrated to be the triggering food.
* Ability to consent to enrollment in the trial - legal guardians with joint consent for patients \>10 years.

Exclusion Criteria:

* Patients with clinical IgE-mediated milk allergy.
* Provisional exclusion: patients without a known IgE-mediated allergic reaction to milk who have a positive RAST (as per local reference range) or positive skin-prick test for cow milk or goat milk must be assessed by a certified allergist/immunologist and cleared for the trial by a supervised goat milk challenge.
* Use of inhaled corticosteroids for more than 5 days per month during the trial period.

Primary outcomes:
measure: Histologic remission rate following 12 weeks exposure to ingested goat's milk products
timeFrame: 12 weeks exposure to ingested goat's milk products
Secondary outcomes:
measure: Symptom scores following 12 weeks exposure to ingested goat's milk
timeFrame: 12 weeks exposure to ingested goat's milk
measure: Endoscopic remission rate following 12 weeks exposure to ingested goat's milk
timeFrame: 12 weeks exposure to ingested goat's milk
measure: Endoscopic improvement following 12 weeks exposure to ingested goat's milk
timeFrame: 12 weeks exposure to ingested goat's milk
measure: Safety of goat's milk challenge
timeFrame: 36 months
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Shaare Zedek
Study officials:
References: