Identifying Young Inflammatory Bowel Disease Patients at Risk for Herpes Zoster

Identify Young Immunosuppressed and Non-immunosuppressed Inflammatory Bowel Disease Patients at Risk for HZ

Inflammatory bowel disease (IBD) patients under the age of 50 can have a greater risk than the general population above age 50. IBD patient are commonly treated with immunosuppression that increases the risk for Herpes Zoster. A new HZ vaccine is available that could decrease the risk of HZ in IBD patients.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis; Herpes Zoster

Detailed Description

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract. A recent national survey from the CDC estimates that the prevalence of IBD in the United States (US) is nearly 3.1 million cases. IBD is often associated with debilitating symptoms, hospitalizations, decreased quality of life, frequent procedures and/or surgery. Treatment options include immunosuppressive therapies, such as corticosteroids, immunomodulators (thiopurines and methotrexate) and anti-tumor necrosis factor alpha (TNF) agents. Although they are effective in achieving clinical remission and decrease the risk of complications, they also increase the risk for serious infections, including herpes zoster (HZ).

The primary goal is to study those patients with IBD who are thought to be at the highest risk for HZ reactivation by evaluating cell mediated immunity (CMI) to VZV.

• Study Type: Observational
• Enrollment (Actual): 97

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Digestive Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

IBD patients with confirmed IBD

Description

Inclusion Criteria:

A history of chronic (greater than 3 month) ulcerative colitis or Crohn's disease diagnosed and documented by the standard clinical, radiographic, endoscopic and histopathologic criteria.

3.12 Ages 40-55 3.13 There will four groups divided by medication group. All patients will be on stable doses of medication for at least 3 months divided in the following groups: A) Group A (24 patients): mesalamine therapy or no IBD therapy B) Group B (12 patients): Thiopurine group: On azathiopurine at least 2.0mg/kg or 6MP 1.0mg/kg C) Group C (12 patients): Anti-TNF therapy group: On maintenance therapy infliximab (at least 8 every 8 weeks), golilumab (at least monthly), adalilumab (at least every 2 weeks), or certolizumab (at least monthly) D) Group D (12 patients): Combination therapy: On anti-TNF therapy as described in group along with either 15mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg 3.14 Previous history of varicella infection verified by positive VZV IgG test. 3.15 The patient must understand and voluntarily sign the informed consent document.

3.16 All participants must have received a tetanus, diphtheria, pertussis (Tdap) or tetanus, diphtheria (Td) within the previous 10 years the Wisconsin Immunization Registry (WIR), will be accessed via the EMR, so confirming immunization will not be a limitation) because tetanus CMI will be used as an experimental control.

Exclusion Criteria:

3.21 Current use of systemic steroids 3.22 Other autoimmune condition (e.g Rheumatoid arthritis, autoimmune hepatitis) 3.23 Receipt of HZ vaccine (As above, via WIR) 3.24 History of cytopenia in the last 12 months (WBC < 3.0 or anemia Hgb <10). (All patients on immunosuppressants routinely obtain blood work every 3-6 months, so this will be available at study entry) 3.25 History of previous herpes zoster infection.

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort
Non-immunosuppressed IBD patients; 24 IBD patients on mesalamine therapy or no IBD therapy
Thiopurine group; 12 IBD patients on azathioprine at least 2.0mg/kg or 6MP 1.0mg/kg
Anti-TNF therapy; 12 IBD patients on maintenance therapy infliximab (at least 8 every 8 weeks), golilumab (at least monthly), adalilumab (at least every 2 weeks), or certolizumab (at least monthly)
Combination therapy; 12 IBD patients on anti-TNF therapy as described in group along with either 15mg of methotrexate or azathioprine at least 1.0mg/kg or 6MP 0.5mg/kg
Healthy Control; The control group with consist of 12 individuals who meet the following inclusion and exclusion criteria. Individuals will be obtained from patients without an IBD diagnosis, chronic liver disease, celiac disease or other chronic health condition coming to Digestive Health Center for endoscopic procedures or clinic visits.
Vedolizumab therarpy; 12 IBD patients on vedolizumab maintenance therapy every 4-8 weeks
Prednisone and Anti-TNF therapy; 12 IBD patients on Anti-TNF maintenance therapy as combination or mono therapy along with at least 10mg of prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response by T cell, cell mediated immunity, to varicella zoster virus in patients with inflammatory bowel disease.	ELISPOT is an enzyme-linked assay for detecting and enumerating cytokine-producing lymphocytes. ELISPOT can detect cytokine-producing cells in as few as 1 in 300,000 cells. ELISPOT is the standard for measuring varicella cell mediated immunity.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response by T cells ,cell Mediated Immunity, to varicella zoster virus in Immunosuppressed patients with IBD compared to those non-Immunosuppressed	ELISPOT is an enzyme-linked assay for detecting and enumerating cytokine-producing lymphocytes. ELISPOT can detect cytokine-producing cells in as few as 1 in 300,000 cells. ELISPOT is the standard for measuring varicella cell mediated immunity.	Day 1
Immune response by T cell, cell mediated immunity, to varicella zoster virus in Immunosuppressed IBD patients compared to other immunosuppressed IBD patients	ELISPOT is an enzyme-linked assay for detecting and enumerating cytokine-producing lymphocytes. ELISPOT can detect cytokine-producing cells in as few as 1 in 300,000 cells. ELISPOT is the standard for measuring varicella .	Day 1

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Freddy Caldera, DO, University of Wisconsin School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): May 31, 2019
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): June 19, 2019
• Last Update Submitted That Met QC Criteria: June 18, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases; Herpes Zoster
• Other Study ID Numbers: 2017-0512

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No