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

Primary Purpose

Celiac Disease

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Gluten

About this trial

This is an interventional other trial for Celiac Disease focused on measuring Gluten Challenge

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Massachusetts General Hospital
Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Group A: Gluten 3 gm

Group B: Gluten 10 gm

Arm Description

Gluten 3 gram (gm), powder, orally, once daily up to 14 days.

Gluten 10 gm, powder, orally, once daily up to 14 days.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT03409796

First Posted

December 31, 2017

Last Updated

May 20, 2022

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT03409796

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

April 24, 2018 (Actual)

Primary Completion Date

May 2, 2019 (Actual)

Study Completion Date

May 2, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Celiac Disease

Keywords

Gluten Challenge

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A: Gluten 3 gm

Arm Type

Other

Arm Description

Gluten 3 gram (gm), powder, orally, once daily up to 14 days.

Arm Title

Group B: Gluten 10 gm

Arm Type

Other

Arm Description

Gluten 10 gm, powder, orally, once daily up to 14 days.

Intervention Type

Dietary Supplement

Intervention Name(s)

Gluten

Intervention Description

Gluten powder.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and Day 15

Title

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

Description

Time Frame

Baseline and Day 15

Secondary Outcome Measure Information:

Title

Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments

Description

Time Frame

At Baseline, Days 6 and 15

Title

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

Description

Time Frame

Baseline and Day 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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.

Citations:

PubMed Identifier

33130104

Citation

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.

Results Reference

derived

Links:

URL

https://clinicaltrials.takeda.com/study-detail/5f6b60374db2bf003ab4a134?idFilter=%5B%22TIMP-GLIA-5001%22%5D

Description

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

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