Celiac DiseaseEarly Phase 1NCT04054544

Gluten Challenge Study in Celiac Disease Participants (MK-0000-402)

A Early Phase 1 study testing Gluten powder 4g in people with Celiac Disease, run by Merck Sharp & Dohme LLC at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a gluten challenge study to characterize peripheral blood and intestinal gluten specific cluster of differentiation 4 glycoprotein (CD4+) thymus lymphocyte (T cell) subsets in participants with Celiac Disease Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Celiac Disease
What is being tested?: Gluten powder 4g
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 2 sitesUnited States
Study dates: 28 Aug 2020to 23 Jun 2021
Phase: Early Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.
Participant must be on a gluten-free diet (GFD) for at least the past 12 months.
Female participants must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must use an acceptable contraceptive method or abstain from heterosexual intercourse.
Must be Human leukocyte antigen (HLA)-DQ2.5 positive, assessed at screening. If participants have already been genotyped, results from previous testing may be used in lieu of genotyping at screening.
Has anti-tissue transglutaminase (anti-tTG) <2x upper limit of normal (ULN) as measured by serology.
Be judged to be in good health based on medical history, physical examination (including a targeted neurological exam), versus (vs.) measurements and electrocardiogram (ECG) performed prior to treatment allocation.
Have a body mass index (BMI) 18-35 kg/m^2, inclusive.

Who cannot join

Has any chronic active gastrointestinal (GI) disease (e.g., clinically active CeD despite being on GFD for past 12 months, Crohn's disease, ulcerative colitis, lymphocytic colitis). Inactive, stable/well-treated lactose intolerance, Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS) are allowed.
Has clinically active endocrine, gastrointestinal (other than CeD), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events or stable medical diseases with no symptoms and stable treatment for the past >3 months may be enrolled in the study at the discretion of the investigator.
Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder within the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
Participant has an estimated Glomerular Filtration Rate (eGFR) ≤80 mL/min/1.73 m^2 at the screening visit based on the Cockcroft-Gault (CG) equation
Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or systemic allergic reaction to prescription or nonprescription drugs or food.
Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion.

Show all 12Show fewer

Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
Is on Coumadin™ or other anticoagulants.
Is unable to refrain from or anticipates the use of systemic anti-inflammatory, immunosuppressive, or immunomodulatory medications, which may include ibuprofen > 2400 mg/day, naproxen >750 mg/day, prednisone >10 mg/day, or methylprednisolone > 8 mg/day, within 48 hours prior to the start of and throughout the entire gluten challenge.
Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit. The window will be derived from the date of the last visit in the previous study.
Has a corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Massachusetts General Hospital ( Site 0001)
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center ( Site 0002)
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Gluten Challenge Study to Characterize Peripheral Blood and Intestinal Gluten-specific CD4+ T Cell Subsets in Patients With Celiac Disease

Read the detailed description

This is a multi-site, open-label gluten challenge study to characterize peripheral blood and intestinal gluten specific CD4+ T cell subsets in participants with celiac disease (CeD). Participants will receive 8 grams (g) of gluten daily for 13 consecutive days. Blood samples will be taken at pre-dose, Day 6, and Day 14. Duodenal biopsy samples will also be collected on Day 14. Participants will also complete a symptom diary.

Conditions: Celiac Disease
Being tested: Gluten powder 4g
Keywords: Celiac disease
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 powder 4gDietary supplement
Gluten powder 4g oral BID

Study groups in NCT04054544
Study group	Role	What they receive
Gluten challenge	Experimental	Participants will receive a gluten 4 g powder twice daily (BID), for 13 consecutive days Receives: Dietary Supplement: Gluten powder 4g

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
Peripheral blood mononuclear cells (PBMC) collected prior to gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Measured: Baseline (Day 1, pre-dose)
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
Peripheral blood mononuclear cells (PBMC) collected on Day 14 following gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Measured: Day 14
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
Lymphocytes from duodenal biopsies collected on Day 14 following gluten challenge were stained with a phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramer (DQ2.5-glia-α1) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. Lymphocytes were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Measured: Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Aug 202023 Jun 2021

First posted13 Aug 2019
Study start28 Aug 2020
Primary completion23 Jun 2021
Study completion23 Jun 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Celiac DiseaseStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe 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: Early Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Model description: Experimental study to determine blood and duodenal T cell changes following administration of an 8 g gluten challenge daily for 13 days in participants with celiac disease
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04054544
Sponsor's protocol ID: 0000-402
Other IDs: MK-0000-402
Status last verified: Jun 2022
First submitted: 5 Aug 2019
Last updated: 6 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Celiac Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Gluten Challenge Study to Characterize Peripheral Blood and Intestinal Gluten-specific CD4+ T Cell Subsets in Patients With Celiac Disease
ClinicalTrials.gov ID: NCT04054544
Acronym / sponsor ID: 0000-402
Conditions: Celiac Disease
Keywords: Celiac disease
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 28 Aug 2020 (actual)
Primary completion: 23 Jun 2021 (actual)
Study completion: 23 Jun 2021 (actual)
First posted: 13 Aug 2019 (actual)
Results: Posted 6 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Experimental study to determine blood and duodenal T cell changes following administration of an 8 g gluten challenge daily for 13 days in participants with celiac disease

Arm	Type	Receives
Gluten challenge	Experimental	Dietary Supplement: Gluten powder 4gParticipants will receive a gluten 4 g powder twice daily (BID), for 13 consecutive days

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.
Participant must be on a gluten-free diet (GFD) for at least the past 12 months.
Female participants must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must use an acceptable contraceptive method or abstain from heterosexual intercourse.
Must be Human leukocyte antigen (HLA)-DQ2.5 positive, assessed at screening. If participants have already been genotyped, results from previous testing may be used in lieu of genotyping at screening.
Has anti-tissue transglutaminase (anti-tTG) <2x upper limit of normal (ULN) as measured by serology.

Key exclusion criteria (12 listed)

Has any chronic active gastrointestinal (GI) disease (e.g., clinically active CeD despite being on GFD for past 12 months, Crohn's disease, ulcerative colitis, lymphocytic colitis). Inactive, stable/well-treated lactose intolerance, Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS) are allowed.
Has clinically active endocrine, gastrointestinal (other than CeD), cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events or stable medical diseases with no symptoms and stable treatment for the past >3 months may be enrolled in the study at the discretion of the investigator.
Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of clinically significant psychiatric disorder within the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
Participant has an estimated Glomerular Filtration Rate (eGFR) ≤80 mL/min/1.73 m^2 at the screening visit based on the Cockcroft-Gault (CG) equation
Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or systemic allergic reaction to prescription or nonprescription drugs or food.

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 powder 4gGluten powder 4g oral BID	Dietary supplement	Gluten challenge

Primary outcome

Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge
Time frame: Baseline (Day 1, pre-dose)
Peripheral blood mononuclear cells (PBMC) collected prior to gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge
Time frame: Day 14
Peripheral blood mononuclear cells (PBMC) collected on Day 14 following gluten challenge were stained with phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramers (DQ2.5-glia-α1 and DQ2.5-glia-α2) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. PBMC were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).
Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge
Time frame: Day 14
Lymphocytes from duodenal biopsies collected on Day 14 following gluten challenge were stained with a phycoerythrin (PE)-labeled human leukocyte antigen (HLA)-DQ2.5: gluten tetramer (DQ2.5-glia-α1) to identify antigen-specific cluster of differentiation (CD)4-positive thymus lymphocyte (T cells) reactive to gliadin (tetramer+ T cells) by flow cytometry. Lymphocytes were also labeled with a 20-antibody panel for cell surface antigen staining to further define tetramer+ T cell subsets. Antigens included in the analysis were CD25, CD38, CD39, programmed cell death receptor 1 (PD-1), and integrin beta-7 (B7).

Results and safety

Results posted to the registry on 6 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Gluten Challenge	18	18

Primary outcome: Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge

Time frame: Baseline (Day 1, pre-dose). Mean (Standard Deviation). Unit: Percentage of T cells

Measure	Gluten Challenge n = 15
α1-gliadin tetramer+	0.00364 (0.00278)
α1-gliadin tetramer+, CD25+	0.00016 (0.00029)
α1-gliadin tetramer+, CD38+	0.00049 (0.00080)
α1-gliadin tetramer+, CD39+	0.00005 (0.00021)
α1-gliadin tetramer+, PD1+	0.00007 (0.00020)
α1-gliadin tetramer+, Integrin B7+	0.00161 (0.00162)
α2-gliadin tetramer+	0.01115 (0.00988)
α2-gliadin tetramer+, CD25+	0.00058 (0.00092)

Population analysed: The analysis population includes participants who were compliant with study procedures and had available data.

Primary outcome: Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood After Gluten Challenge

Time frame: Day 14. Mean (Standard Deviation). Unit: Percentage of T cells

Measure	Gluten Challenge n = 15
α1-gliadin tetramer+	0.00707 (0.00510)
α1-gliadin tetramer+, CD25+	0.00054 (0.00071)
α1-gliadin tetramer+, CD38+	0.00276 (0.00161)
α1-gliadin tetramer+, CD39+	0.00049 (0.00075)
α1-gliadin tetramer+, PD1+	0.00091 (0.00113)
α1-gliadin tetramer+, Integrin B7+	0.00361 (0.00198)
α2-gliadin tetramer+	0.01315 (0.01199)
α2-gliadin tetramer+, CD25+	0.00177 (0.00391)

Population analysed: The analysis population includes participants who were compliant with study procedures and had available data.

Primary outcome: Percentage of α1-gliadin-reactive CD4+ T Cells in Duodenal Biopsies After Gluten Challenge

Time frame: Day 14. Mean (Standard Deviation). Unit: Percentage of T cells

Measure	Gluten Challenge n = 15
α1-gliadin tetramer+	0.29347 (0.26689)
α1-gliadin tetramer+, CD25+	0.00263 (0.00401)
α1-gliadin tetramer+, CD38+	0.19977 (0.19001)
α1-gliadin tetramer+, CD39+	0.21248 (0.24696)
α1-gliadin tetramer+, PD1+	0.26563 (0.26510)
α1-gliadin tetramer+, Integrin B7+	0.24281 (0.24192)

Population analysed: The analysis population includes participants who were compliant with study procedures and had available data.

Adverse events

Time frame: Up to 27 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Gluten Challenge	0 of 18 (0%)	16 of 18 (88.9%)	0 of 18

Limitations and caveats (from the sponsor): Due to unavailability of appropriate reagents, planned flow cytometry analyses of ω-gliadin reactivity and prevalence of CD95, tumor growth factor β1 receptor (TGFβ1R), and interleukin-27 receptor (IL-27R) antigens could not be performed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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.

Medical Director study director

Merck Sharp & Dohme LLC

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Gluten powder 4g in people with Celiac Disease, run by Merck Sharp & Dohme LLC at 2 sites 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 7 inclusion and 12 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 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of α1- and α2-gliadin-reactive CD4+ T Cells in Peripheral Blood Before Gluten Challenge (time frame: Baseline (Day 1, pre-dose)). 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?

On the ClinicalTrials.gov record for NCT04054544.

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 6 Mar 2023.