A Decentralized Home-Based Study To Investigate Novel Objective Biomarker Of Gluten-Mediated Symptoms In Celiac Disease Participants (CeDar ROSE Study)

Study Overview
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Brief Summary
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This is a decentralized study to primarily explore a novel objective digital biomarker (i.e., Gluten Dependency Index) for celiac disease-related responses triggered by gluten exposure using a wearable biosensor. This study also explores a novel objective blood biomarker specific to celiac disease activity and evaluates participant symptoms, lifestyle and an objective comprehensive measurement (e.g., activity, stress and sleep) in celiac disease participants. Approximately 170 well-controlled celiac disease participants (Cohort A) and 40 celiac disease participants with persistent symptoms (Cohort B) will be monitored for 13 and 8 weeks in the observation period, respectively, in a home-based setting using the wearable biosensor along with a mobile platform including some electronic questionnaires. The wearable biosensor continuously records biosensor data. These data will be used to develop a new algorithm for Gluten Dependency Index and calculate the Gluten Dependency Index, Activity Value, Stress Value, or Sleep Time. Participants will report celiac disease-related symptoms, diet (including any accidental gluten exposures), exercise, menstruation questionnaires in CDSD and mobile platform questionnaire (MPFQ), which is originally designed by the Sponsor. All participants both in Cohort A and B are required to maintain gluten-free diet throughout the study. Only participant who are enrolled in Cohort A will be required gluten challenge.

Official Title
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A Decentralized Home-Based Study To Investigate Novel Objective Biomarker Of Gluten-Mediated Symptoms Using A Wearable Biosensor And A Mobile Platform In Celiac Disease Participants With And Without Gluten Challenge (CeDar ROSE Study)

Conditions
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Celiac Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: [Cohort A and B] History of medically diagnosed celiac disease based on biopsies and positive celiac serology. Be on a GFD for at least 12 months Willing and able to adhere to use and management of the wearable device Willingness to comply with home-based approach and visits by a HN professional [Cohort A only] Experienced at most mild symptoms of celiac disease Willingness to consume food containing up to 6 g of gluten protein per challenge day and up to 18 g of gluten protein in total during the study [Cohort B only] Experienced at least 2 different gluten-related symptoms (e.g., diarrhea, abdominal pain, bloating, nausea, tiredness) or 1 gluten-related symptom occurred twice within the month before screening, and at screening were required to have a qualifying score as moderate or severe on at least one symptom on the CDSD in the 14 days recording period. Positive for any of the 3 serology tests, tissue - transglutaminase-2-IgA [tTG2-IgA] (≥4 U/mL), deamidated gliadin peptide-IgA [DGP-IgA] (≥20 U/mL), or deamidated gliadin peptide-IgG [DGP-IgG] (≥20U/mL) Exclusion Criteria: [Cohort A and B] Refractory celiac disease [Cohort A] Positive for any of the 3 serology tests Tissue transglutaminase-2 [tTG2-IgA] (≥10 U/mL; normal range: 0-3.99 U/mL) prior to the observation period, but weak positive (4-10 U/mL) can be enrolled in this study. Deamidated gliadin peptide-IgA [DGP-IgA], and deamidated gliadin peptide-IgG [DGP-IgG] prior to the observation period, but weak positive (20-30 U/mL) can be enrolled. History of IgE-mediated reactions to wheat, barley, rye, or other ingredients in the gluten products used in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A: Well-controlled Celiac Disease<br>Cohort A: Well-controlled celiac disease participants who should be asymptomatic or mildly symptomatic | |
| Cohort B: Non-Responsive Celiac Disease<br>Cohort B: Celiac disease participants with persistent symptoms who are known to be symptomatic and show positivity to serum auto-antibodies even though participants have been adhering to gluten-free diet | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The concordance between the novel digital biomarker and the presence of celiac disease-related symptoms |  | up to 13 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlations between the comprehensive measurement and the scores of patient reported outcomes | Correlations between the comprehensive measurement and the scores of Celiac Disease Symptom Diary (CDSD), 36-Item Short Form Survey (SF-36), or Celiac Disease-related Quality of Life (CDQOL) | up to 13 weeks | 
| The comprehensive measurement | The comprehensive measurement objectively evaluated by wearable biosensor | up to 13 weeks | 
| The scores of Celiac Disease Symptom Diary (CDSD) | Scoring rate for celiac disease symptoms Minimum: Non Maximum: Very severe | up to 13 weeks | 
| The scores of Short Form 36 (SF-36) | Scoring rate for quality of life (higher score-better quality of life) Minimum: 0 Maximum: 100 | up to 13 weeks | 
| The scores of Celiac Disease-related Quality of Life (CDQOL) | Scoring rate for quality of life in celiac disease participants Minimum: 1 (total disagreement) Maximum: 5 (total agreement) | up to 13 weeks | 
| Adverse events | Incidence and severity of adverse events | up to 13 weeks | 
| Adverse events' relationship to gluten exposure | Incidence and severity of adverse events' relationship to gluten exposure | up to 13 weeks | 
| Safety as assessed by systolic and diastolic by blood pressure | Abnormality in blood pressure | up to 13 weeks | 
| Safety as assessed by body temperature | Abnormality in body temperature | up to 13 weeks | 
| Safety as assessed by pulse rate | Abnormality in pulse rate | up to 13 weeks | 
| Safety as assessed by respiratory rate | Abnormality in respiratory rate | up to 13 weeks | 
| Safety as assessed by percutaneous oxygen saturation | Abnormality in percutaneous oxygen saturation | up to 13 weeks | 
| Safety as assessed by hematology test with counting blood cells | Incidence of hematology abnormalities | up to 13 weeks | 
| Safety as assessed by blood chemistry test with measuring chemicals | Incidence of blood chemistry abnormalities | up to 13 weeks | 
| Safety as assessed by coagulation testing with thrombolytic capacity measurement | Incidence of coagulation abnormalities | up to 13 weeks | 
| Safety as assessed by urinalysis test with examining the visual, chemical and microscopic aspects | Incidence of urinalysis abnormalities | up to 13 weeks | 
| Safety as assessed by Electrocardiograms (QT interval) | Abnormality in QT interval | up to 13 weeks | 
| Safety as assessed by Electrocardiograms (heart rate) | Abnormality in heart rate | up to 13 weeks | 
| Celiac disease serology levels | Serology levels about tissue transglutaminase-2-IgA (tTG2-IgA; unit/mL) | up to 13 weeks | 
| Celiac disease serology levels | Serology levels about Deamidated gliadin peptide-IgA (DGP-IgA; unit), and deamidated gliadin peptide-IgG (DGP-IgG; unit) | up to 13 weeks | 
| 3072 Blood biomarkers profile | 3072 Blood biomarkers profile measured by proteomics in well-controlled celiac disease participants (Cohort A) and in celiac disease participants with persistent symptoms (Cohort B) | up to 13 weeks | 
| 48 Blood biomarker profile | 48 Blood biomarkers profile measured by proteomics in well-controlled celiac disease participants (Cohort A) and in celiac disease participants with persistent symptoms (Cohort B) | up to 13 weeks | 
| Change from baseline in 3072 blood biomarkers profile (Cohort A only) | Change from baseline in 3072 blood biomarker profile measured by proteomics after gluten/sham gluten challenge (Cohort A only) | up to 13 weeks | 
| Change from baseline in 48 blood biomarkers profile (Cohort A only) | Change from baseline in 48 blood biomarkers profile measured by proteomics after gluten/sham gluten challenge (Cohort A only) | up to 13 weeks | 
| The incidence of novel digital biomarker (Cohort B only) | The incidence of novel digital biomarker established in Cohort A (Cohort B only) | up to 13 weeks |