Single-cell Immune Response to Controlled Gluten Ingestion in Pediatric Celiac Disease

Summary

This study investigates how the immune system of children with celiac disease responds to controlled, small amounts of gluten. Children on a strict gluten-free diet are randomly assigned to receive either placebo, 50 mg of gluten, or 5 g of gluten once daily for three days, simulating real-life accidental exposure or dietary transgression. Blood samples are collected on Day 1 (before gluten intake) and Day 8 (five days after the last dose). Stool and urine samples are also collected for complementary analyses.

Using single-cell ribonucleic acid (RNA) sequencing, T-cell receptor sequencing, microRNA profiling, and exploratory metabolomics, the study aims to characterize changes in immune cell populations and gene expression after gluten exposure. The objective is to determine whether even very small amounts of gluten induce measurable systemic immune responses and whether these responses differ according to the dose administered. Understanding these mechanisms may support the development of new biomarkers and improve clinical management of pediatric celiac disease.

Conditions

• Celiac Disease
• Gluten Sensitivity
• Autoimmune Diseases

Interventions

DIETARY_SUPPLEMENT

Placebo

Placebo preparation identical in appearance and administration schedule to gluten doses. Administered once daily on Days 1, 2, and 3. Used as the comparator. Participants and evaluators remain blinded to allocation.

DIETARY_SUPPLEMENT

Gluten 50 mg

Participants receive 50 mg of gluten once daily on Days 1, 2, and 3. This dose simulates accidental low-level gluten exposure in children with celiac disease. Participants and evaluators remain blinded to allocation.

DIETARY_SUPPLEMENT

Gluten 5 g

Participants receive 5 g of gluten once daily on Days 1, 2, and 3. This dose simulates a dietary transgression in children with celiac disease. Participants and evaluators remain blinded to allocation.

PROCEDURE

Collection of blood, stool and urine samples on Day 1 and Day 8.

In addition to blood samples, stool and urine samples will be collected for complementary analyses (including fecal gluten immunogenic peptides (GIP) and exploratory metabolomic assays)

Sponsors & Collaborators

• Hospital Regional de Malaga

  collaborator OTHER

• Andaluz Health Service

  collaborator OTHER_GOV

• Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental

  collaborator OTHER

• Universidad de Málaga

  collaborator UNKNOWN

• Consorcio Centro de Investigación Biomédica en Red (CIBER)

  collaborator OTHER_GOV

• Biohealth Research Institute in Granada (ibs.GRANADA)

  collaborator UNKNOWN

• Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

  lead OTHER

Principal Investigators

• Rafael Martín Masot, MD, PhD · Hospital Regional Universitario de Málaga / IBIMA-BIONAND

• Lara María Bossini Castillo, MD, PhD · IBS Granada

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

8 Years

Max Age

14 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-07

Primary Completion

2026-04-30

Completion

2026-11-30

Countries

• Spain

Study Locations