Assessment of Immune Activation and Tolerance in Celiac Disease During Gluten Challenge
2 other identifiers
interventional
16
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Apr 2018
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 31, 2017
CompletedFirst Posted
Study publicly available on registry
January 24, 2018
CompletedStudy Start
First participant enrolled
April 24, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
May 2, 2019
CompletedResults Posted
Study results publicly available
August 18, 2020
CompletedMay 24, 2022
May 1, 2022
1 year
December 31, 2017
April 30, 2020
May 20, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio
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 and Day 15
Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts
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 and Day 15
Secondary Outcomes (2)
Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
At Baseline, Days 6 and 15
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
Baseline and Day 6
Study Arms (2)
Group A: Gluten 3 gm
OTHERGluten 3 gram (gm), powder, orally, once daily up to 14 days.
Group B: Gluten 10 gm
OTHERGluten 10 gm, powder, orally, once daily up to 14 days.
Interventions
Eligibility Criteria
You may qualify if:
- Be a non-smoker who has not used tobacco- or nicotine-containing products (example, nicotine patch) for at least 6 months before Day 1 gluten administration.
- Have well-controlled biopsy-proven CeD, compliant with a gluten-free diet (GFD) for greater than or equal to (\>=) 6 months preceding screening, with resolution of CeD symptoms, normalization of CeD serology, and in the judgment of the investigator, have inactive or minimally-active disease.
- Be HLA-DQ2.5 and/or HLA-DQ8 positive, assessed at screening. If participants have already been genotyped, results from previous testing may be used in lieu of genotyping at screening.
- Be willing to delay a planned procedure involving the use of powerful electromagnetic fields (example, magnetic resonance imaging), until the PillCam SB 3 capsule is excreted.
- Not undergo VCE or optical coherence tomography (OCT) if has an implanted electromedical device or a swallowing disorder.
- Not undergo OCT if has a contraindication to the device or procedure as per reference information.
You may not qualify if:
- Had major surgery and/or donated or lost 1 unit of blood (approximately 500 milliliter \[mL\]) within 8 weeks before the first dose of gluten.
- Are unable to refrain from or anticipate the use of any unapproved medication, including prescription drugs, nonprescription drugs, and herbal remedies, beginning approximately 7 days before administration of the initial dose of gluten and continuing throughout the trial until the follow-up visit.
- Consume excessive amounts of coffee, tea, cola, energy drinks, or other caffeinated beverages per day. An excessive amount is defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine).
- Have positive IgA anti-tissue transglutaminase (tTG), IgA anti-deamidated gliadin peptide (DGP), and IgG DGP serologies at Screening.
- Have inflammatory gastrointestinal disorders or autoimmune diseases other than CeD or autoimmune thyroid disease.
- Have known or suspected gastrointestinal obstructions, strictures, or fistulas based on the clinical picture or pre-procedure testing and profile of the PillCam SB 3 capsule.
- Endoscopy and intestinal biopsy are contraindicated.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (2)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Related Publications (2)
Johansen A, Sandve GKF, Maxwell JR, Smithson G, Sollid LM, Stamnaes J. Biopsy Proteome Score Performs Well as an Effect Measure in a Gluten Challenge Trial of Celiac Disease. Clin Gastroenterol Hepatol. 2025 Apr;23(5):758-765.e8. doi: 10.1016/j.cgh.2024.08.005. Epub 2024 Aug 30.
PMID: 39209203DERIVEDLeonard MM, Silvester JA, Leffler D, Fasano A, Kelly CP, Lewis SK, Goldsmith JD, Greenblatt E, Kwok WW, McAuliffe WJ, Galinsky K, Siegelman J, Chow IT, Wagner JA, Sapone A, Smithson G. Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial. Gastroenterology. 2021 Feb;160(3):720-733.e8. doi: 10.1053/j.gastro.2020.10.040. Epub 2020 Oct 29.
PMID: 33130104DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 31, 2017
First Posted
January 24, 2018
Study Start
April 24, 2018
Primary Completion
May 2, 2019
Study Completion
May 2, 2019
Last Updated
May 24, 2022
Results First Posted
August 18, 2020
Record last verified: 2022-05
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.