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

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04828031

Collaborator

Doris Duke Charitable Foundation (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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 .

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases Ulcerative Colitis Crohn Disease	Drug: Vitamin D	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

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/mLOpen 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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D 50,000 IU PO every week Vitamin D 50,000 IU PO every week for 12 weeks	Drug: Vitamin 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.

Arm

Intervention/Treatment

Experimental: Vitamin D 50,000 IU PO every week

Vitamin D 50,000 IU PO every week for 12 weeks

Drug: Vitamin 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

Stanford University
Doris Duke Charitable Foundation

Investigators

Principal Investigator: John Mark Gubatan, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

John Gubatan, Fellow in Gastroenterology, Stanford University

ClinicalTrials.gov Identifier:

NCT04828031

Other Study ID Numbers:

IRB-60958

First Posted:

Apr 1, 2021

Last Update Posted:

Jul 27, 2021

Last Verified:

Jul 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by John Gubatan, Fellow in Gastroenterology, Stanford University

Gut Microbiome, Vitamin D, Dysbiosis, Inflammation

Additional relevant MeSH terms:

Crohn Disease

Intestinal Diseases

Inflammatory Bowel Diseases

Vitamin D

Study Results

No Results Posted as of Jul 27, 2021