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

Celiac Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04614571
• Other study ID #: 0000-CD-CES-1880
• Status: Recruiting
• Phase: N/A
• Start date: November 2, 2020
• Est. completion date: September 30, 2024

Study information

• Verified date: September 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key 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

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Dietary Supplement:
• Gluten Powder
Administered orally daily for 14 days

Locations

Country	Name	City	State
United States	Celiac Research Centre Mass General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells	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.	Baseline and Day 15
Secondary	Change from Baseline in Small Intestine Histology Based on Villous Height (Microns), Crypt Depth (Microns) and Villous Height to Crypt Depth Ratio (Vh:Cd)	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.	Baseline and Day 15
Secondary	Identification and ex vivo functional validation of gluten-specific T cells	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	Up to 30 days post challenge