Vitamin D Regulation of Gut Specific B Cells and Antibodies Targeting Gut Bacteria in Inflammatory Bowel Disease

Study Overview
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Brief Summary
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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 .

Official Title
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Vitamin D Regulation of α4β7+ B Cell Immunophenotypes and Mucosal Antibody Response to Commensal Gut Bacteria in Patients With Inflammatory Bowel Disease

Conditions
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Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease

Intervention / Treatment
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* Drug: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18 years or older) with inflammatory bowel disease (ulcerative colitis or Crohn's disease) Low serum vitamin D (25(OH)D ≤ 25 ng/mL Not currently on high dose vitamin D supplementation No prior bowel resections No antibiotic use in past 3 months. Exclusion Criteria: Patients less than 18 years old No diagnosis of IBD Serum 25(OH)D > 25 ng/mL Patients already on vitamin D supplementation Prior history of bowel surgery (colectomy or small bowel resections) Recent antibiotic use in past 3 months Renal Dysfunction History of Hypercalcemia History of HIV History of IgA deficiency History of Common Variable Immunodeficiency (CVID) Active C. diff infection

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D 50,000 IU PO every week<br>Vitamin D 50,000 IU PO every week for 12 weeks | Drug: Vitamin D<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut Microbiome, Vitamin D, Dysbiosis, Inflammation