Iron Deficiency in Pediatric Celiac Disease: Diet vs. Iron Supplementation Trial

Official title

Iron Deficiency Without Anemia in Children With Newly Diagnosed Celiac Disease: A Randomized, Open-Label, Controlled Trial.

Overview

This study aims to understand how to best manage iron deficiency in children newly diagnosed with celiac disease. Many children with celiac disease have low iron levels, even if they do not have anemia. While some doctors recommend iron supplements, others believe that simply following a gluten-free diet may be enough to restore iron levels naturally. In this study, children with newly diagnosed celiac disease and low iron levels (but normal hemoglobin) will be randomly assigned to one of two groups: Gluten-Free Diet Only - No additional iron supplements Gluten-Free Diet + Iron Supplementation Researchers will compare iron store levels over one year to see if iron supplements provide any additional benefit beyond the gluten-free diet alone. The study will also track possible side effects of iron supplements, such as stomach discomfort. This study will help doctors determine the best approach to managing iron deficiency in children with celiac disease, ensuring they receive the safest and most effective treatment.

Detailed description

This is a prospective, randomized, controlled, open-label, non-inferiority trial designed to evaluate the necessity of iron supplementation in children newly diagnosed with celiac disease and iron deficiency without anemia. The study will compare two treatment strategies:

Gluten-Free Diet Alone Gluten-Free Diet + Iron Supplementation The primary objective is to determine whether a gluten-free diet alone is sufficient to restore ferritin levels or if iron supplementation provides a significant additional benefit.

Study Design \& Methods Eligible participants will be randomly assigned to one of the two treatment groups.

Ferritin levels will be monitored at baseline, 4 months, and 12 months to assess improvements.

The study will also evaluate patient adherence to a gluten-free diet and iron supplementation, quality of life, as well as the incidence of gastrointestinal side effects related to iron supplement use.

This study is expected to provide evidence-based guidance for the management of iron deficiency in pediatric celiac disease, addressing a gap in current clinical recommendations.

Interventions

• Drug Iron (III) Hydroxide Polymaltose (50 mg/5 mL)
  Participants randomized to the intervention group will receive oral iron supplementation in addition to a gluten-free diet. The specific iron formulation used in this study is Iron (III) Hydroxide Polymaltose (50 mg/5 mL) at a dosage of 6 mg/kg/day, up to a maximum of 100 mg/day, for 3 months. The iron supplement will be given once daily, preferably on an empty stomach or with vitamin C-containing foods to enhance absorption. Parents/caregivers will be instructed on proper administration, and a
• Other Gluten-free diet
  Participants in the control group will follow a strict gluten-free diet, the standard-of-care treatment for celiac disease. No iron supplementation will be given. Compliance will be monitored through self-reported adherence and TTG antibody levels at follow-up.

Primary outcome measures

• Change in ferritin levels from baseline to 12 months [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]

Secondary outcome measures (12)

• Change in Anti-TTG antibody levels [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Self-reported adherence to gluten-free diet [Time frame: Weekly (for intervention group up to 12 weeks), monthly (via phone, control arm, up to 12 weeks)), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Adherence to iron supplementation (intervention group only) [Time frame: Weekly up to 3 months after enrollment]
• Percentage of participants with ferritin ≥15 ng/mL at 12 Months [Time frame: 12 months (±1 month) after enrollment]
• Change in weight [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Gastrointestinal symptoms evaluation [Time frame: Weekly (Intervention Group Only up to 12 weeks)), 4 Months (±1 month), 12 Months (±1 month) after enrollment]
• Evaluation of hemoglobin levels for anemia [Time frame: 4 months (±1 month), 12 months (±1 month) after enrollment]
• Association of H. pylori at diagnosis with GI symptoms [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Change in height [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Change in BMI [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Association of H. pylori at diagnosis with Ferritin levels over time [Time frame: At baseline (Day 0), 4 months (±1 month), and 12 months (±1 month) after enrollment]
• Change in anti-TTG IgA antibody levels as an indicator of adherence to gluten-free diet [Time frame: At 4 months (±1 month) and 12 months (±1 month) after enrollment]

Eligibility criteria

Inclusion criteria

• Children aged 18 months to 18 years
• Newly diagnosed with celiac disease (based on ESPGHAN guidelines)
• Ferritin levels below 15 ng/dL
• Normal hemoglobin, MCV, and MCH levels for age and sex

Exclusion criteria

• IgA deficiency preventing TTG antibody monitoring
• Potential celiac disease (positive serology with normal intestinal histology)
• Underlying diseases that may cause anemia (e.g., Inflammatory bowel disease, eosinophilic gastrointestinal disease, certain gastritis types)
• Diseases affecting iron absorption (e.g., Cystic Fibrosis)
• Congenital anemia (e.g., Thalassemia, hereditary spherocytosis)
• Prior iron supplementation (>14 days oral iron within 2 months or IV iron within 6 months before diagnosis)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Israel · 5 centers

• Assuta Ashdod Medical Center — Ashdod
• Rambam Medical Center — Haifa
• Meir Medical Center — Kfar Saba
• Schneider Children's Medical Center — Petah Tikva
• Kaplan Medical Center — Rehovot

Publications

• Ben-Ami T, Trotskovsky A, Topf-Olivestone C, Kori M. Iron deficiency without anemia in children with newly diagnosed celiac disease: 1-year follow-up of ferritin levels, with and without iron supplementation. Eur J Pediatr. 2024 Nov;183(11):4705-4710. doi: 10.1007/s00431-024-05721-1. Epub 2024 Aug 27. PMID 39190044

Identifiers

NCT: NCT06921343 · KMC-25-0038

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗