Gluten Challenge Study in Celiac Disease Participants (MK-0000-402)
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Gluten challenge Participants will receive a gluten 4 g powder twice daily (BID), for 13 consecutive days |
Dietary Supplement: Gluten powder 4g
Gluten powder 4g oral BID
|
Outcome Measures
Primary Outcome Measures
- α-gliadin and ω-gliadin-reactive CD4+ T cells in peripheral blood before gluten challenge [Baseline]
Percentage of α-gliadin and ω-gliadin-reactive CD+4 T cells expressing known activation and inhibitory receptors including but not limited to: CD25 (IL-2R), CD95 (FasR), CD279 (PD-1), TGFb1R, and IL- 27R)) in peripheral blood cells before gluten challenge.
- α-gliadin and ω-gliadin-reactive CD4+ T cells in peripheral blood after gluten challenge [Day 14]
Percentage of α-gliadin and ω-gliadin-reactive CD+4 T cells expressing known activation and inhibitory receptors including but not limited to: CD25 (IL-2R), CD95 (FasR), CD279 (PD-1), TGFb1R, and IL- 27R)) in peripheral blood cells after gluten challenge.
- α-gliadin and ω-gliadin-reactive CD4+ T cells in duodenal biopsies after gluten challenge [Day 14]
Percentage of α-gliadin and ω-gliadin-reactive CD+4 T cells expressing known activation and inhibitory receptors including but not limited to: CD25 (IL-2R), CD95 (FasR), CD279 (PD-1), TGFb1R, and IL- 27R)) in duodenal cells after gluten challenge.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must have documented diagnosis with celiac disease (CeD) by duodenal/jejunal biopsy at least 6 months prior to entrance into the study.
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Participant must be on a gluten-free diet (GFD) for at least the past 12 months.
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Female participants must not be pregnant or breastfeeding. Women of childbearing potential (WOCBP) must use an acceptable contraceptive method or abstain from heterosexual intercourse.
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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.
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Has anti-tissue transglutaminase (anti-tTG) <2x upper limit of normal (ULN) as measured by serology.
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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.
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Have a body mass index (BMI) 18-35 kg/m2, inclusive.
Exclusion Criteria:
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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.
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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.
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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.
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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
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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.
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Subject has a history of severe acute symptomatic reactions to sporadic gluten ingestion.
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Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
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Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
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Is on Coumadin™ or other anticoagulants.
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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.
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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.
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Has a corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital ( Site 0001) | Boston | Massachusetts | United States | 02114 |
| 2 | Beth Israel Deaconess Medical Center ( Site 0002) | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0000-402
- MK-0000-402