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

Primary Purpose

Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Vitamin D
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inflammatory Bowel Diseases focused on measuring Gut Microbiome, Vitamin D, Dysbiosis, Inflammation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vitamin D 50,000 IU PO every week

Arm Description

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

Outcomes

Primary Outcome Measures

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)
Reduction in immunoglobulin coating of commensal gut bacteria by 20%.
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
25(OH)D will be measured from serum by standard laboratory assay (HPLC)
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
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

Full Information

First Posted
March 29, 2021
Last Updated
September 19, 2023
Sponsor
Stanford University
Collaborators
Doris Duke Charitable Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04828031
Brief Title
Vitamin D Regulation of Gut Specific B Cells and Antibodies Targeting Gut Bacteria in Inflammatory Bowel Disease
Official Title
Vitamin D Regulation of α4β7+ B Cell Immunophenotypes and Mucosal Antibody Response to Commensal Gut Bacteria in Patients With Inflammatory Bowel Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
July 1, 2023 (Actual)
Study Completion Date
July 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Doris Duke Charitable Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. 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 .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn Disease
Keywords
Gut Microbiome, Vitamin D, Dysbiosis, Inflammation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vitamin D 50,000 IU PO every week
Arm Type
Experimental
Arm Description
Vitamin D 50,000 IU PO every week for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Vitamin D
Intervention Description
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.
Primary Outcome Measure Information:
Title
Reduction in α4β7+ B cells by 20%
Description
Expression of gut tropic integrin α4β7+ on B cells assessed at gene expression level (single cell transcriptomics) and protein level (cytometry)
Time Frame
Week 12
Title
Reduction in immunoglobulin coating of commensal gut bacteria by 20%.
Description
Immunoglobulin coating of gut bacteria will be measured from stool samples using Ig-Seq
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Increase in serum vitamin D (25(OH)D levels by 10 ng/mL
Description
25(OH)D will be measured from serum by standard laboratory assay (HPLC)
Time Frame
Week 12
Title
Decrease in disease activity index scores by 50%
Description
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
Time Frame
Week 12
Title
Decrease cohort mean fecal calprotectin or C-reactive protein (CRP) by 50%.
Description
Fecal calprotectin will be measured from stool samples. CRP will be measured from plasma
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Mark Gubatan, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
28831186
Citation
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.
Results Reference
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PubMed Identifier
32005980
Citation
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.
Results Reference
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PubMed Identifier
31203722
Citation
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.
Results Reference
background
PubMed Identifier
30876876
Citation
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.
Results Reference
background
PubMed Identifier
31647134
Citation
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.
Results Reference
background
PubMed Identifier
27266980
Citation
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.
Results Reference
background
PubMed Identifier
29762159
Citation
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.
Results Reference
background
PubMed Identifier
17259988
Citation
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.
Results Reference
background
PubMed Identifier
34180967
Citation
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.
Results Reference
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Vitamin D Regulation of Gut Specific B Cells and Antibodies Targeting Gut Bacteria in Inflammatory Bowel Disease

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