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

NCT04614571 | Completed

• 1 other identifier: 0000-CD-CES-1880
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Celiac Disease

Keywords

CeD; HLA-DQ2 positive; HLA-DQ8 positive

Outcome Measures

Primary Outcomes (3)

• Change from Baseline in small intestine TCR repertoire

  Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in the small intestine after gluten challenge

  Up to 30 days post challenge

• Change from Baseline in peripheral blood TCR repertoire

  Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in peripheral blood after gluten challenge

  Up to 30 days post challenge

• Changes from baseline in small intestine and peripheral blood transcriptome

  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

  Up to 30 days post challenge

Secondary Outcomes (3)

• Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells

  Baseline and Day 15

• 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

• Identification and ex vivo functional validation of gluten-specific T cells

  Up to 30 days post challenge

Study Arms (1)

Gluten Challenge

OTHER

Dietary Supplement: Gluten Powder

Interventions

Gluten Powder DIETARY_SUPPLEMENT

Administered orally daily for 14 days

Gluten Challenge

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• 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
• Have participated in another investigational trial within 4 weeks before Screening
• Have a history of cancer (malignancy) other than nonmelanoma skin cancer
• Have a history of significant multiple and/or severe allergies (e.g., latex allergy)
• Presence of HIV (HIV Ab), hepatitis B (HBsAg, HBAb) or Hepatitis C (HCV Ab) seropositivity at screening
• Ongoing immunosuppression or receive any treatment that might alter T cell repertoire or phenotype

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (1)

Celiac Research Centre Mass General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Clinical Trial Administrator

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: November 4, 2020
• Study Start: November 2, 2020
• Primary Completion: May 30, 2024
• Study Completion: May 30, 2024
• Last Updated: June 27, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

Locations

US (1)