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Completed

NCT Number: NCT04614571

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

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

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Key information

Conditions

Celiac Disease Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Malabsorption Syndromes Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Celiac Research Centre Mass General Hospital

Boston, Massachusetts, 02114, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

Note: Other protocol-defined inclusion/ exclusion criteria apply

Treatment and study plan

Gluten Powder

Dietary Supplement

Administered orally daily for 14 days

Primary outcomes

  1. Change from Baseline in small intestine TCR repertoire

    Time frame: 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

  2. Change from Baseline in peripheral blood TCR repertoire

    Time frame: 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

  3. Changes from baseline in small intestine and peripheral blood transcriptome

    Time frame: 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

Secondary outcomes

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

    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 are defined as the last observed value before the first dose of gluten.

  2. Change from Baseline in Small Intestine Histology Based on Villous Height (Microns), Crypt Depth (Microns) and Villous Height to Crypt Depth Ratio (Vh:Cd)

    Time frame: 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.

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

    Time frame: 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

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

TCR Sequencing and Transcriptional Profiling in Celiac Disease Patients Undergoing Gluten Challenge

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Nov 4, 2020
Registry last updated
Jun 27, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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