T Cell Receptor (TCR) Sequencing and Transcriptional Profiling in Adult Celiac Disease Patients Undergoing Gluten Challenge

Not Applicable

Completed

• Conditions: Celiac Disease
• Interventions: Dietary Supplement: Gluten Powder

• Registration Number: NCT04614571
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

The primary objectives are:

* Characterize the T cell receptor (TCR) repertoire in duodenal biopsy samples of participants pre- and post-challenge.

* Compare for each patient the TCR repertoire of duodenal biopsy samples with the peripheral blood TCR repertoire of each study participant

* Characterize the transcriptome of duodenal biopsy samples and blood from study participants pre- and post-challenge

The secondary objectives are:

* Ex vivo identification and validation of DQ-restricted gliadin specific TCRs.

* Characterize the gluten-challenge induced changes in small intestine histology using standard for Celiac Disease (CeD) histological assessments

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-24
• Study First Submitted QC: 2020-10-28
• Study Start: 2020-11-02
• Study First Posted: 2020-11-04
• Primary Completion: 2024-05-30
• Study Completion: 2024-05-30
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-26
• Last Update Posted: 2024-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Have a body mass index (BMI) ≥17 and ≤40 kg/m2 and a body weight >45 kg at the Screening Visit
2. Be judged to be in good health as defined in the protocol
3. Have well-controlled biopsy-proven CeD, compliant with a GFD for ≥6 months preceding Screening as defined in the protocol
4. Be HLA-DQ2 and/or HLA-DQ8 positive as defined in the protocol

Key

Exclusion Criteria

1. Have a history of gluten triggered acute symptoms (≤24 hours after gluten exposure), and/or severe symptoms (abdominal pain interfering with daily activities, diarrhea with >5 stools/day), and/or prolonged symptoms (duration >7 days)
2. Have a history of clinically significant endocrine, cardiovascular, hematological, hepatic, immunological (other than CeD or autoimmune thyroid disease), renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or disease
3. Have participated in another investigational trial within 4 weeks before Screening
4. Have a history of cancer (malignancy) other than nonmelanoma skin cancer
5. Have a history of significant multiple and/or severe allergies (e.g., latex allergy)
6. Presence of HIV (HIV Ab), hepatitis B (HBsAg, HBAb) or Hepatitis C (HCV Ab) seropositivity at screening
7. Ongoing immunosuppression or receive any treatment that might alter T cell repertoire or phenotype

Note: Other protocol-defined inclusion/ exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gluten Challenge	Gluten Powder	-

Primary Outcome Measures

Name	Time	Method
Change from Baseline in peripheral blood TCR repertoire	Up to 30 days post challenge	Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in peripheral blood after gluten challenge
Changes from baseline in small intestine and peripheral blood transcriptome	Up to 30 days post challenge	Change in the gene expression profile (transcriptomic analysis by ribonucleic acid \[RNA\] sequencing and cellular indexing of transcriptomes and epitopes by sequencing \[CITEseq\]) of the small intestine and peripheral blood after gluten challenge
Change from Baseline in small intestine TCR repertoire	Up to 30 days post challenge	Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in the small intestine after gluten challenge

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Small Intestine Histology Based on Villous Height (Microns), Crypt Depth (Microns) and Villous Height to Crypt Depth Ratio (Vh:Cd)	Baseline and Day 15	Villi are the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in active CeD. Crypts are grooves between the villi that are often elongated in CeD. A decreased Vh:Cd ratio indicates more extreme CeD disease symptoms. Baseline values (Microns) will be defined as the last observed value before the first dose of gluten.
Identification and ex vivo functional validation of gluten-specific T cells	Up to 30 days post challenge	Clonality of peripheral blood mononuclear cell (PBMC)-derived gluten-specific T cells (measured by T cell receptor sequencing) after ex vivo expansion with gluten peptides
Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells	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 are defined as the last observed value before the first dose of gluten.

Trial Locations

Locations (1)

Celiac Research Centre Mass General Hospital; 🇺🇸 Boston, Massachusetts, United States