Crohn Disease, Inflammatory Bowel Diseases, Ulcerative Colitis
Conditions
Keywords
Gut Microbiome, Vitamin D, Dysbiosis, Inflammation
Brief summary
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 .
Interventions
DRUGVitamin D
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.
Sponsors
Doris Duke Charitable Foundation
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in α4β7+ B cells by 20% | Week 12 | Expression of gut tropic integrin α4β7+ on B cells assessed at gene expression level (single cell transcriptomics) and protein level (cytometry) |
| Reduction in immunoglobulin coating of commensal gut bacteria by 20%. | Week 12 | Immunoglobulin coating of gut bacteria will be measured from stool samples using Ig-Seq |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increase in serum vitamin D (25(OH)D levels by 10 ng/mL | Week 12 | 25(OH)D will be measured from serum by standard laboratory assay (HPLC) |
| Decrease in disease activity index scores by 50% | Week 12 | 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 |
| Decrease cohort mean fecal calprotectin or C-reactive protein (CRP) by 50%. | Week 12 | Fecal calprotectin will be measured from stool samples. CRP will be measured from plasma |
Countries
United States
Outcome results
None listed