Celiac DiseaseNCT04614571
T Cell Receptor (TCR) Sequencing and Transcriptional Profiling in Adult Celiac Disease Patients Undergoing Gluten Challenge
A study testing Gluten Powder in people with Celiac Disease, run by Regeneron Pharmaceuticals at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Gluten Powder
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2020to 30 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Celiac Research Centre Mass General Hospital
Boston, Massachusetts, 02114
About this study
Official title: TCR Sequencing and Transcriptional Profiling in 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
- Conditions
- Celiac Disease
- Being tested
- Gluten Powder
- Keywords
- CeD, HLA-DQ2 positive, HLA-DQ8 positive
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gluten PowderDietary supplement
Administered orally daily for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Gluten Challenge | Other | Not described Receives: Dietary Supplement: Gluten Powder |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
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.
Measured: 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)
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.
Measured: Baseline and Day 15
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
Measured: Up to 30 days post challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start2 Nov 2020
- Primary completion30 May 2024
- Study completion30 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Celiac DiseaseStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Administrator, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04614571
- Sponsor's protocol ID
- 0000-CD-CES-1880
- Status last verified
- Jun 2024
- First submitted
- 24 Sep 2020
- Last updated
- 27 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TCR Sequencing and Transcriptional Profiling in Celiac Disease Patients Undergoing Gluten Challenge
- ClinicalTrials.gov ID
- NCT04614571
- Acronym / sponsor ID
- 0000-CD-CES-1880
- Conditions
- Celiac Disease
- Keywords
- CeD, HLA-DQ2 positive, HLA-DQ8 positive
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 30 May 2024 (actual)
- First posted
- 4 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gluten Challenge | Other | Dietary Supplement: Gluten Powder |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gluten PowderAdministered orally daily for 14 days | Dietary supplement | Gluten Challenge |
Primary outcome
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
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
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
3 secondary outcomes
Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells
Time frame: 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)
Time frame: Baseline and Day 15
Identification and ex vivo functional validation of gluten-specific T cells
Time frame: Up to 30 days post challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2024.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Administrator study director
Regeneron Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gluten Powder in people with Celiac Disease, run by Regeneron Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in small intestine TCR repertoire (time frame: Up to 30 days post challenge). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2024.