Back to results

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

Primary Purpose

Celiac Disease

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Gluten Powder

About this trial

This is an interventional other trial for Celiac Disease focused on measuring CeD, HLA-DQ2 positive, HLA-DQ8 positive

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 a nonsmoker who has not used tobacco- or nicotine-containing products (e.g., nicotine patch) for at least 6 months before Day 1 gluten administration
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-DQ2.5 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

Sites / Locations

Celiac Research Centre Mass General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Gluten Challenge

Arm Description

Outcomes

Primary Outcome Measures

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

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

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

Secondary Outcome Measures

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.

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.

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

Full Information

NCT ID

NCT04614571

First Posted

September 24, 2020

Last Updated

September 11, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04614571

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 2, 2020 (Actual)

Primary Completion Date

September 30, 2024 (Anticipated)

Study Completion Date

September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Celiac Disease

Keywords

CeD, HLA-DQ2 positive, HLA-DQ8 positive

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gluten Challenge

Arm Type

Other

Intervention Type

Dietary Supplement

Intervention Name(s)

Gluten Powder

Intervention Description

Administered orally daily for 14 days

Primary Outcome Measure Information:

Title

Change from Baseline in small intestine TCR repertoire

Description

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

Time Frame

Up to 30 days post challenge

Title

Change from Baseline in peripheral blood TCR repertoire

Description

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

Time Frame

Up to 30 days post challenge

Title

Changes from baseline in small intestine and peripheral blood transcriptome

Description

Time Frame

Up to 30 days post challenge

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and Day 15

Title

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

Description

Time Frame

Baseline and Day 15

Title

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

Description

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

Time Frame

Up to 30 days post challenge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Clinical Trials Administrator

Phone

844-734-6643

clinicaltrials@regeneron.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Administrator

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Celiac Research Centre Mass General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Individual Site Status

Recruiting

Facility Contact:

Phone

617-643-5546

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing 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.

IPD Sharing 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

IPD Sharing URL

https://vivli.org/

Learn more about this trial

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

We'll reach out to this number within 24 hrs