Celiac DiseaseNCT03409796

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

A study testing Gluten in people with Celiac Disease, run by Takeda at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Celiac Disease
What is being tested?: Gluten
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 2 sitesUnited States
Study dates: 24 Apr 2018to 2 May 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

Read the detailed description

Gluten challenge studies are used to test the effectiveness of therapies designed to prevent immune response to gluten in participants with CeD. The study will enroll approximately 20 participants. Participants will be randomly assigned (by chance, like flipping a coin) in a 1:1 ratio to one of the two treatment groups:

Group A: Gluten 3 gm
Group B: Gluten 10 gm

All participants will be asked to take an oral dose of gluten at the same time on Days 1 to 14 throughout the study. This multi-center trial will be conducted in the United States. The overall time to participate in this study is 10 weeks. Participants will visit to the clinic on Day -45 and will be contacted for follow-up assessment on Days 15 to 42.

Conditions: Celiac Disease
Being tested: Gluten
Keywords: Gluten Challenge
Medical subject headings: Celiac Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GlutenDietary supplement
Gluten powder.

Study groups in NCT03409796
Study group	Role	What they receive
Group A: Gluten 3 gm	Other	Gluten 3 gram (gm), powder, orally, once daily up to 14 days. Receives: Dietary Supplement: Gluten
Group B: Gluten 10 gm	Other	Gluten 10 gm, powder, orally, once daily up to 14 days. Receives: Dietary Supplement: Gluten

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Baseline and Day 15

Secondary outcomes (2)

Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
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 intestine where they function to preserve integrity of mucosal barrier by protecting epithelium against pathogen/immune-induced pathology. Decreased Vh:Cd ratio and increased IELs count indicated more extreme CeD symptoms. Baseline value: last observed value before first dose of gluten. Tr: T cell value taken before first dose of gluten. T6: T cell value at Day 6. T15: T cell value at Day 15.
Measured: 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
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.
Measured: Baseline and Day 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Apr 20182 May 2019

First posted24 Jan 2018
Study start24 Apr 2018
Primary completion2 May 2019
Study completion2 May 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Celiac DiseaseStudies of the same condition, open and under way.
More trials run by TakedaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03409796
Sponsor's protocol ID: TIMP-GLIA-5001
Other IDs: U1111-1202-6708
Status last verified: May 2022
First submitted: 31 Dec 2017
Last updated: 24 May 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: 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.

Publications

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.
PubMed 39209203
Leonard 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.
PubMed 33130104

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Celiac Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Immune Activation and Tolerance in Celiac Disease During Gluten Challenge
ClinicalTrials.gov ID: NCT03409796
Acronym / sponsor ID: TIMP-GLIA-5001
Conditions: Celiac Disease
Keywords: Gluten Challenge
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: TakedaIndustry (pharma, biotech, devices)
Study start: 24 Apr 2018 (actual)
Primary completion: 2 May 2019 (actual)
Study completion: 2 May 2019 (actual)
First posted: 24 Jan 2018 (actual)
Results: Posted 18 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Group A: Gluten 3 gm
Group B: Gluten 10 gm

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Group A: Gluten 3 gm	Other	Dietary Supplement: GlutenGluten 3 gram (gm), powder, orally, once daily up to 14 days.
Group B: Gluten 10 gm	Other	Dietary Supplement: GlutenGluten 10 gm, powder, orally, once daily up to 14 days.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GlutenGluten powder.	Dietary supplement	Group A: Gluten 3 gm, Group B: Gluten 10 gm

Primary outcome

Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio
Time frame: 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.
Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts
Time frame: 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.

2 secondary outcomes

Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
Time frame: 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
Time frame: Baseline and Day 6

Results and safety

Results posted to the registry on 18 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A: Gluten 3 Gram	9	7
Group B: Gluten 10 Gram	7	6

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

Time frame: Baseline and Day 15. Mean (Standard Deviation). Unit: ratio

Measure	Group A: Gluten 3 Gram n = 7	Group B: Gluten 10 Gram n = 7
Baseline	2.10 (0.697)	2.30 (0.893)
Change at Day 15	-0.06 (0.516)	-1.53 (0.941)

Group A: Gluten 3 Gram: p = 0.385, t-test, 1 sided
Group B: Gluten 10 Gram: p = 0.003, t-test, 1 sided

Population analysed: The biomarker analysis set consisted of all participants had two endoscopic examinations with biopsies, one before and one after gluten challenge.

Primary outcome: Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts

Time frame: Baseline and Day 15. Mean (Standard Deviation). Unit: IEL per 100 epithelial cells

Measure	Group A: Gluten 3 Gram n = 7	Group B: Gluten 10 Gram n = 7
Baseline	26.74 (15.861)	26.68 (8.248)
Change at Day 15	9.56 (15.206)	26.80 (14.908)

Group A: Gluten 3 Gram: p = 0.010, Poisson distribution
Group B: Gluten 10 Gram: p = 0.006, Poisson distribution

Population analysed: The biomarker analysis set consisted of all participants who had two endoscopic examinations with biopsies, one before and one after gluten challenge.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Treatment emergent adverse events (TEAEs) are adverse events that started after the first dose of gluten up to Day 43. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A: Gluten 3 Gram	0 of 9 (0%)	3 of 9 (33.3%)	0 of 9
Group B: Gluten 10 Gram	0 of 7 (0%)	1 of 7 (14.3%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39209203Johansen 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.
Derived from this study: PubMed 33130104Leonard 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.
To obtain more information about this study, click this link.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. 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.

Related trials for Celiac Disease

Active, not recruitingEarly Phase 1
VTP-1000 in Adults With Celiac Disease
Celiac Disease
RecruitingObservational study
Impact of Mediterranean Diet and Processed Food Consumption on Gastrointestinal Symptoms in Coeliac Patients on a Gluten-Free Diet
Celiac Disease, Gluten-free Diet
Recruiting
GF-NOURISH (Gluten Free Nutrition Optimization Through Ultra-processed Food Reduction and Improved Strategies for Health)
Celiac Disease in Children, Nutrition Disorder, Child
RecruitingObservational study
Celiac Disease Genomic Environmental Microbiome and Metabolomic Study
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Pathogenic Study of Adult Immune Enteropathies
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director Clinical Science study director

Takeda

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Gluten in people with Celiac Disease, run by Takeda at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio (time frame: Baseline and Day 15). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03409796, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2022.