NCT03409796

Assessment of Immune Activation and Tolerance in Celiac Disease During Gluten Challenge

Completed NA Results posted Last updated 24 May 2022

What this trial tests

NA trial testing Gluten in Celiac Disease in 16 participants. Completed in 2 May 2019.

Timeline

24 April 2018

Primary endpoint
2 May 2019

2 May 2019

Quick facts

Lead sponsor	Takeda
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	other
Enrollment	16
Start date	24 April 2018
Primary completion	2 May 2019
Estimated completion	2 May 2019
Sites	2 locations across United States

Drugs / interventions tested

• Gluten

Conditions studied

• Celiac Disease — all drugs for Celiac Disease →

Sponsor

Takeda — full company profile →

Who can join

Adults 18 to 75, any sex, with Celiac Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio Primary · Baseline and Day 15

Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 15 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CeD. Crypts were grooves between the villi that are often elongated in participants with CeD. A decreased Vh:Cd ratio indicates more extreme CeD disease symptoms. Baseline values was defined as the last observed value before the first dose of gluten.

Baseline

Group	Value	95% CI
Group A: Gluten 3 Gram	2.10	± 0.697
Group B: Gluten 10 Gram	2.30	± 0.893

Change at Day 15

Group	Value	95% CI
Group A: Gluten 3 Gram	-0.06	± 0.516
Group B: Gluten 10 Gram	-1.53	± 0.941

Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts Primary · Baseline and Day 15

IELs are white blood cells (WBCs) interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased IELs count indicated more extreme CeD disease symptoms. Baseline values was defined as the last observed value before the first dose of gluten.

Baseline

Group	Value	95% CI
Group A: Gluten 3 Gram	26.74	± 15.861
Group B: Gluten 10 Gram	26.68	± 8.248

Change at Day 15

Group	Value	95% CI
Group A: Gluten 3 Gram	9.56	± 15.206
Group B: Gluten 10 Gram	26.80	± 14.908

Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments Secondary · At Baseline, Days 6 and 15

Standard measures used for diagnosing CeD: Vh:CD ratio and IEL counts. T cell measurements taken before first dose of gluten were correlated with Baseline Vh:Cd ratio and IEL counts, and T cell measurements taken after first dose of gluten were correlated with Day 15 Vh:Cd ratio and IEL counts using Spearman correlation. Villi were small finger like projections that line small intestine, promote nutrient absorption and are often shortened in CeD participants. Crypts were grooves between villi that were often elongated in CeD participants. IELs were WBCs interspersed between epithelial cells of

Tr: Baseline Vh:Cd ratio

Group	Value	95% CI
Group A: Gluten 3 Gram	-0.0355
Group B: Gluten 10 Gram	0.1480

Tr: Baseline IEL counts

Group	Value	95% CI
Group A: Gluten 3 Gram	-0.0050
Group B: Gluten 10 Gram	-0.0905

T6: Day 15 Vh: Cd ratio

Group	Value	95% CI
Group A: Gluten 3 Gram	0.0368
Group B: Gluten 10 Gram	-0.0170

T6: Day 15 IEL counts

Group	Value	95% CI
Group A: Gluten 3 Gram	0.2179
Group B: Gluten 10 Gram	0.0595

T15: Day 15 Vh: Cd ratio

Group	Value	95% CI
Group A: Gluten 3 Gram	-0.0913
Group B: Gluten 10 Gram	0.0214

T15: Day 15 IEL counts

Group	Value	95% CI
Group A: Gluten 3 Gram	0.2967
Group B: Gluten 10 Gram	0.0192

Change From Baseline in Gluten-specific T Cells in Blood Based on Enzyme-linked Immune Absorbent Spot (ELISPot) Assay and T Cell Receptor (TCR) Human Leukocyte Antigen Serotype (HLA-DQ2)-Tetramers Secondary · Baseline and Day 6

ELISpot assay and gluten specific TCR measures drug response by quantifying changes in the number or function of gluten-specific T cells. Baseline value was defined as the last observed value before the first dose of gluten.

Baseline (ELISpot)

Group	Value	95% CI
Group A: Gluten 3 Gram	1.00	± 1.956
Group B: Gluten 10 Gram	1.45	± 1.756

Change at Day 6 (ELISpot)

Group	Value	95% CI
Group A: Gluten 3 Gram	3.83	± 6.902
Group B: Gluten 10 Gram	25.12	± 29.025

Baseline (Tetramer)

Group	Value	95% CI
Group A: Gluten 3 Gram	34.62	± 29.215
Group B: Gluten 10 Gram	17.33	± 14.894

Change at Day 6 (Tetramer)

Group	Value	95% CI
Group A: Gluten 3 Gram	26.76	± 54.084
Group B: Gluten 10 Gram	522.47	± 788.177

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group A: Gluten 3 Gram

Serious: 0/9 (0%)

Deaths: 0/9

Group B: Gluten 10 Gram

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (4 terms — click to expand)

Reaction	System	Group A: Gluten 3 Gram	Group B: Gluten 10 Gram
Vomiting	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Gluten sensitivity	Metabolism and nutrition disorders	—	—

Data from ClinicalTrials.gov NCT03409796 adverse events section.

Sponsor's own description

The primary purpose of this study is to characterize changes in gluten-specific T cells and pathology in the small intestine with specific focus on biomarkers likely to change with therapeutic celiac disease (CeD) treatment.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial.
   Leonard MM, Silvester JA, Leffler D, Fasano A, et al · · 2021 · cited 68× · PMID 33130104 · DOI 10.1053/j.gastro.2020.10.040
2. Gluten Degrading Enzymes for Treatment of Celiac Disease.
   Wei G, Helmerhorst EJ, Darwish G, Blumenkranz G, et al · · 2020 · cited 48× · PMID 32679754 · DOI 10.3390/nu12072095
3. Gut microbiota in Celiac Disease: microbes, metabolites, pathways and therapeutics.
   Olshan KL, Leonard MM, Serena G, Zomorrodi AR, et al · · 2020 · cited 26× · PMID 33103934 · DOI 10.1080/1744666x.2021.1840354
4. A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing Both Morphology and Inflammation.
   Syage JA, Mäki M, Leffler DA, Silvester JA, et al · · 2024 · cited 5× · PMID 37952751 · DOI 10.1016/j.cgh.2023.10.031
5. Biopsy Proteome Score Performs Well as an Effect Measure in a Gluten Challenge Trial of Celiac Disease.
   Johansen A, Sandve GKF, Maxwell JR, Smithson G, et al · · 2025 · cited 3× · PMID 39209203 · DOI 10.1016/j.cgh.2024.08.005
6. New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.
   Dipasquale V, Romano C. · · 2025 · cited 2× · PMID 40281872 · DOI 10.3390/healthcare13080923