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

NCT04828031 | Completed Phase 1 FDA Drug

• 1 other identifier: IRB-60958
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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 .

Conditions

Inflammatory Bowel Diseases; Ulcerative Colitis; Crohn Disease

Keywords

Gut Microbiome, Vitamin D, Dysbiosis, Inflammation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Increase in serum vitamin D (25(OH)D levels by 10 ng/mL

  Week 12

• Decrease in disease activity index scores by 50%

  Week 12

• Decrease cohort mean fecal calprotectin or C-reactive protein (CRP) by 50%.

  Week 12

Study Arms (1)

Vitamin D 50,000 IU PO every week

EXPERIMENTAL

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

Drug: Vitamin D

Interventions

Vitamin D DRUG

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.

Vitamin D 50,000 IU PO every week

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (9)

• 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.

  PMID: 28831186 BACKGROUND

• 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.

  PMID: 32005980 BACKGROUND

• 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.

  PMID: 31203722 BACKGROUND

• 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.

  PMID: 30876876 BACKGROUND

• 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.

  PMID: 31647134 BACKGROUND

• 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.

  PMID: 27266980 BACKGROUND

• 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.

  PMID: 29762159 BACKGROUND

• 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.

  PMID: 17259988 BACKGROUND

• 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.

  PMID: 34180967 BACKGROUND

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Dysbiosis; Inflammation

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• John Mark Gubatan, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow in Gastroenterology

Model Details: 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

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 1, 2021
• Study Start: July 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

US (1)