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

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


Lead sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
Brief 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

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.

Overall Status Not yet recruiting
Start Date July 13, 2020
Completion Date January 26, 2021
Primary Completion Date January 26, 2021
Phase Early Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
α-gliadin and ω-gliadin-reactive CD4+ T cells in peripheral blood before gluten challenge Baseline
α-gliadin and ω-gliadin-reactive CD4+ T cells in peripheral blood after gluten challenge Day 14
α-gliadin and ω-gliadin-reactive CD4+ T cells in duodenal biopsies after gluten challenge Day 14
Enrollment 15

Intervention type: Dietary Supplement

Intervention name: Gluten powder 4g

Description: Gluten powder 4g oral BID

Arm group label: Gluten challenge



Inclusion Criteria:

1. Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.

2. Participant must be on a gluten-free diet (GFD) for at least the past 12 months.

3. Female participants must not be a woman of childbearing potential (WOCBP), pregnant or breastfeeding

4. 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.

5. Has anti-tissue transglutaminase (anti-tTG) <2x upper limit of normal (ULN) as measured by serology.

6. 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.

7. Have a body mass index (BMI) 18-35 kg/m2, inclusive.

Exclusion Criteria:

1. Has any chronic active gastrointestinal (GI) disease (eg, 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.

2. 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.

3. 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.

4. Participant has an estimated Glomerular Filtration Rate (eGFR) ≤80 mL/min/1.73 m2 at the screening visit based on the Cockcroft-Gault (CG) equation

5. Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or systemic allergic reaction to prescription or nonprescription drugs or food.

6. Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion.

7. Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).

8. Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.

9. Is on Coumadin™ or other anticoagulants.

10. 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.

11. 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.

12. Has a corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Merck, Sharpe & Dohme Corp.
Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Gluten challenge

Arm group type: Experimental

Description: Participants will receive a gluten 4 g powder twice daily (BID), for 13 consecutive days

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: Experimental study to determine blood and duodenal T cell changes following administration of a 8 g gluten challenge daily for 13 days in participants with celiac disease

Primary purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov