Effects of Swallowed Steroids on Bone Density and Growth in Pediatric Eosinophilic Esophagitis

Effects of Swallowed Corticosteroids on Bone Mineral Density and Growth Velocity in Children With Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is characterized by allergy-driven inflammation of the esophagus leading to a variety of gastrointestinal symptoms and increased healthcare utilization. While considered a rare disease, EoE is rapidly increasing in prevalence in the United States. Treatment options are limited and include dietary modifications with the elimination of suspected food triggers or pharmacological options including proton pump inhibitors (PPIs) and swallowed corticosteroids. Compliance to strict elimination diets is difficult thus many patients elect to use swallowed corticosteroids. Because nearly half of all EoE patients are treated with swallowed corticosteroids there is a growing concern regarding the long-term effects of this class of medication.4

It is known that oral corticosteroids can compromise bone mineral density and growth velocity5-7. Furthermore, there have been multiple studies exploring the relationship between inhaled corticosteroids (ICS) and endocrine effects in asthmatics. While the risk of ICS use is less compared to systemic corticosteroids, higher ICS doses do cause deleterious effects on growth and bone health8-11. Currently, there are no published studies examining the effect of swallowed corticosteroids on bone mineral density or growth velocity in patients with EoE. Given the route of administration, there may be more systemic absorption leading to a higher risk of long-term complications.

The proposed work will address the following specific aims:

Specific Aim 1: Assess effects of swallowed corticosteroids on bone mineral density (primary outcome) in children 5-12 years of age with EoE compared to age matched controls.

Specific Aim 2: Evaluation of the effect of swallowed corticosteroids on growth velocity.

Study Overview

• Status: Unknown
• Conditions: Eosinophilic Esophagitis
• Intervention / Treatment: Diagnostic test: Bone Mineral Density (DEXA) scan; Diagnostic test: Vitamin D Measurement; Diagnostic test: Height measurement; Other: Assessment of medication compliance

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Robbie Pesek, MD; Phone Number: 5013641060; Email: rdpesek@uams.edu
• Study Contact Backup: Name: April Hickman; Phone Number: 5013641060; Email: AMHickman@uams.edu

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
      • Contact: Robbie Pesek; Phone Number: 501-364-1060; Email: rdpesek@uams.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will recruit 30 children, ages 5-12 years, with eosinophilic esophagitis (EoE) and 30 age and sex-matched controls from the Arkansas Children's Hospital allergy clinic to participate in this prospective study. Controls will be age- and gender-matched in a 1:1 ratio with EoE subjects but will not be required to have a diagnosis of EoE. Control subjects will not be treated with swallowed corticosteroids.

Description

Inclusion Criteria:

• Intervention:

  1. Age 5-12 years
  2. Diagnosis of EoE based upon a peak eosinophil count of ≥ 15 eosinophils/high powered field (hpf) on at least one esophageal biopsy while on a minimum of 8 weeks of PPI therapy
  3. Patient/Family has elected to start swallowed corticosteroids for the treatment of EoE with a minimum daily dose of at least 0.5 mg budesonide or 440 mcg fluticasone. The decision to start swallowed corticosteroids will be made based upon the judgement of the provider, potential subject, and family during a clinic visit and will not be part of the research procedures.

• Controls:

  1. Age 5-12 years
  2. Followed in the ACH allergy clinic, but not required to have a diagnosis of EoE
  3. Not treated with swallowed corticosteroids

Exclusion Criteria:

• Intervention and controls:

  1. Non-English speaking
  2. Patients actively taking systemic corticosteroids or previous use of systemic corticosteroids within the past 6 months
  3. Patients actively taking inhaled corticosteroids or prior use of inhaled corticosteroids in the 6 months prior to screening
  4. Current or previous treatment with swallowed corticosteroids for EoE at the time of screening
  5. Osteopenia or osteoporosis on baseline dual energy X-ray absorptiometry (DEXA).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intervention Group; 30 Children with eosinophilic esophagitis who are started on swallowed corticosteroids by their clinical provider.	Diagnostic test: Bone Mineral Density (DEXA) scan; Radiologic assessment of bone mineral density in the lumbar spine. This will be performed at screening. If abnormal at screening, subjects will not be enrolled. For enrolled subjects, DEXA will be repeated at 12 months.; Diagnostic test: Vitamin D Measurement; Measurement of 25-hydroxy vitamin D levels through the blood at baseline and 12 months. If low for age, subjects will receive dietary counseling to increase intake to recommended levels. Primary care providers of enrolled subjects will be notified of abnormal results.; Diagnostic test: Height measurement; Height will be measured at baseline and 12 months.; Other: Assessment of medication compliance; Subjects enrolled in the intervention group will undergo assessment of compliance with swallowed corticosteroids prescribed by their clinical provider. This will be performed at 6 and 12 months.
Control Group; 30 children, 5-12 years of age, not taking swallowed corticosteroids. Age and sex matched 1:1 with intervention group.	Diagnostic test: Bone Mineral Density (DEXA) scan; Radiologic assessment of bone mineral density in the lumbar spine. This will be performed at screening. If abnormal at screening, subjects will not be enrolled. For enrolled subjects, DEXA will be repeated at 12 months.; Diagnostic test: Vitamin D Measurement; Measurement of 25-hydroxy vitamin D levels through the blood at baseline and 12 months. If low for age, subjects will receive dietary counseling to increase intake to recommended levels. Primary care providers of enrolled subjects will be notified of abnormal results.; Diagnostic test: Height measurement; Height will be measured at baseline and 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of swallowed corticosteroids on bone mineral density	Change in bone mineral density over 1 year while being treated with swallowed corticosteroids compared to age-matched controls	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of swallowed corticosteroids on linear growth	Changes in linear growth over 1 year while being treated with swallowed corticosteroids compared to controls	12 months

Collaborators and Investigators

• Sponsor: Arkansas Children's Hospital Research Institute
• Collaborators: University of Arkansas

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2019
• Primary Completion (ANTICIPATED): August 1, 2020
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (ACTUAL): August 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: ACHEOEBMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No