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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04828031
• Other study ID #: IRB-60958
• Status: Completed
• Phase: Phase 1
• Start date: July 1, 2021
• Est. completion date: July 1, 2023

Study information

• Verified date: September 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcerative Colitis

Intervention

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.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Doris Duke Charitable Foundation

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in a4ß7+ B cells by 20%	Expression of gut tropic integrin a4ß7+ on B cells assessed at gene expression level (single cell transcriptomics) and protein level (cytometry)	Week 12
Primary	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	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
Secondary	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
Secondary	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