Clinical trial NCT03409796: 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
Overall status: COMPLETED
Phase: NA
Conditions: Celiac Disease
Keywords: Gluten Challenge
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-01-24
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. Not undergo VCE or optical coherence tomography (OCT) if has an implanted electromedical device or a swallowing disorder.
6. Not undergo OCT if has a contraindication to the device or procedure as per reference information.

Exclusion Criteria:

1. 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.
2. 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.
3. 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).
4. Have positive IgA anti-tissue transglutaminase (tTG), IgA anti-deamidated gliadin peptide (DGP), and IgG DGP serologies at Screening.
5. Have inflammatory gastrointestinal disorders or autoimmune diseases other than CeD or autoimmune thyroid disease.
6. 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.
7. Endoscopy and intestinal biopsy are contraindicated.

Primary outcomes:
measure: Change From Baseline in Small Intestine Histology Based on Villous Height to Crypt Depth (Vh:Cd) Ratio
timeFrame: Baseline and Day 15
measure: Change From Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Counts
timeFrame: Baseline and Day 15
Secondary outcomes:
measure: Correlation Coefficient Changes Between Gluten-specific Blood T Cells and Standard CeD Histological Assessments
timeFrame: At Baseline, Days 6 and 15
measure: 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
timeFrame: Baseline and Day 6
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
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.