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| Name | Class |
|---|---|
| Doris Duke Charitable Foundation | OTHER |
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Specific Aim 1: Characterize the effects of vitamin D treatment on expression of α4β7 on B cells in patients with inflammatory bowel disease (IBD).
Specific Aim 2: Determine the effects of vitamin D treatment on fecal immunoglobulins, percentage of Ig-coated gut bacteria, gut microbiome composition (global and bound by immunoglobulins) in patients with IBD and the association of these parameters with change in α4β7+ B cells .
Specific Aim 3: Compare BCR repertoire (BCR clonotypes, immunoglobulin heavy chain gene (IGHV), and isotype usage) between α4β7+ and α4β7- B cells in patients with IBD and identify α4β7+ BCR clonotypes associated with Ig-bound gut bacteria .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D 50,000 IU PO every week | Experimental | Vitamin D 50,000 IU PO every week for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D | Drug | Patient with inflammatory bowel disease who have low vitamin D (25(OH)D less than or equal to 25 ng/mL) will take Vitamin D 50,000 IU by mouth every week for 12 weeks. Patients will fill out questionnaires to document disease activity score (HBI or Mayo score and sIBDQ) and have blood and stool samples collected before (Week 0), during (Week 8) and after (Week 12) vitamin D intervention. |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in α4β7+ B cells by 20% | Expression of gut tropic integrin α4β7+ on B cells assessed at gene expression level (single cell transcriptomics) and protein level (cytometry) | Week 12 |
| Reduction in immunoglobulin coating of commensal gut bacteria by 20%. | Immunoglobulin coating of gut bacteria will be measured from stool samples using Ig-Seq | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Increase in serum vitamin D (25(OH)D levels by 10 ng/mL | 25(OH)D will be measured from serum by standard laboratory assay (HPLC) | Week 12 |
| Decrease in disease activity index scores by 50% | Disease activity index scores will be measured by Harvey Bradshaw Index in Crohn's disease patients and Mayo Score disease activity index in ulcerative colitis patients |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Mark Gubatan, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28831186 | Background | de Souza HSP, Fiocchi C, Iliopoulos D. The IBD interactome: an integrated view of aetiology, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol. 2017 Dec;14(12):739-749. doi: 10.1038/nrgastro.2017.110. Epub 2017 Aug 23. | |
| 32005980 | Background | Caruso R, Lo BC, Nunez G. Host-microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020 Jul;20(7):411-426. doi: 10.1038/s41577-019-0268-7. Epub 2020 Jan 31. |
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| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D003093 | Colitis, Ulcerative |
| D003424 | Crohn Disease |
| D064806 | Dysbiosis |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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Open label prospective clinical trial with vitamin D 50,000 IU PO every week for 12 weeks in patients with inflammatory bowel disease (IBD) with 25(OH)D ≤ 25 ng/mL
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|
| Week 12 |
| Decrease cohort mean fecal calprotectin or C-reactive protein (CRP) by 50%. | Fecal calprotectin will be measured from stool samples. CRP will be measured from plasma | Week 12 |
| 31203722 | Background | Rengarajan S, Vivio EE, Parkes M, Peterson DA, Roberson EDO, Newberry RD, Ciorba MA, Hsieh CS. Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease. Gut Microbes. 2020 May 3;11(3):405-420. doi: 10.1080/19490976.2019.1626683. Epub 2019 Jun 16. |
| 30876876 | Background | Castro-Dopico T, Dennison TW, Ferdinand JR, Mathews RJ, Fleming A, Clift D, Stewart BJ, Jing C, Strongili K, Labzin LI, Monk EJM, Saeb-Parsy K, Bryant CE, Clare S, Parkes M, Clatworthy MR. Anti-commensal IgG Drives Intestinal Inflammation and Type 17 Immunity in Ulcerative Colitis. Immunity. 2019 Apr 16;50(4):1099-1114.e10. doi: 10.1016/j.immuni.2019.02.006. Epub 2019 Mar 12. |
| 31647134 | Background | Gubatan J, Chou ND, Nielsen OH, Moss AC. Systematic review with meta-analysis: association of vitamin D status with clinical outcomes in adult patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2019 Dec;50(11-12):1146-1158. doi: 10.1111/apt.15506. Epub 2019 Oct 24. |
| 27266980 | Background | Gubatan J, Mitsuhashi S, Zenlea T, Rosenberg L, Robson S, Moss AC. Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2017 Feb;15(2):240-246.e1. doi: 10.1016/j.cgh.2016.05.035. Epub 2016 Jun 4. |
| 29762159 | Background | Gubatan J, Moss AC. Vitamin D in inflammatory bowel disease: more than just a supplement. Curr Opin Gastroenterol. 2018 Jul;34(4):217-225. doi: 10.1097/MOG.0000000000000449. |
| 17259988 | Background | Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, Butcher EC. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007 Mar;8(3):285-93. doi: 10.1038/ni1433. Epub 2007 Jan 28. |
| 34180967 | Background | Gubatan J, Rubin SJS, Bai L, Haileselassie Y, Levitte S, Balabanis T, Patel A, Sharma A, Sinha SR, Habtezion A. Vitamin D Is Associated with alpha4beta7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease. J Crohns Colitis. 2021 Dec 18;15(12):1980-1990. doi: 10.1093/ecco-jcc/jjab114. |
| 41895287 | Derived | Gubatan J, Sojwal RS, Ye J, Boye TL, Hoang JN, Fardeen T, Temby M, Rubin SJS, Spencer SP, Kotagiri P, Rogalla S, Rosen MJ, Nielsen OH, Boyd S, Sonnenburg J, Sinha SR. Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease. Cell Rep Med. 2026 Apr 21;7(4):102703. doi: 10.1016/j.xcrm.2026.102703. Epub 2026 Mar 26. |
| D003092 | Colitis |
| D003108 | Colonic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |