CVD 38000: Study of Responses to Vaccination With Typhoid and/or Cholera

CVD 38000: Immunity, Microbiome, Epigenetics, and a Systems Biology Approach to the Study of Responses to Vaccination With Typhoid and/or Cholera

This is an open-label, non-randomized study. The purpose of this study is to better understand how vaccines against typhoid fever and cholera affect the normal immune system and bacteria in the intestine. Patients having standard-of-care endoscopies (colonoscopy and/or esophagogastroduodenoscopy (EGD)) will be divided into 3 groups:

Group 1: Vivotif typhoid vaccination and/or Vaxchora cholera vaccination then endoscopy Group 2: Endoscopy, then Vivotif typhoid vaccination and/or Vaxchora cholera vaccination, then follow-up endoscopy Group 3: Endoscopy without vaccination.

Both vaccines used in this study are licensed by the Food and Drug Administration (FDA) for travelers to developing countries. Volunteers will be asked to donate tissue, blood, saliva and stool samples for studying how the body responds to the typhoid and/or cholera vaccine.

Study Overview

• Status: Recruiting
• Conditions: Typhoid and/or Cholera Vaccination
• Intervention / Treatment: Drug: Vivotif Typhoid Oral Vaccine; Drug: Vaxchora

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Susan Holian, RN; Phone Number: 410-706-6156; Email: susan.holian@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland, Baltimore, Center for Vaccine Development and Global Health
      • Contact: Susan Holian, RN; Email: susan.holian@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1. Age 18 years and older
• 2. Already scheduled to undergo an EGD or colonoscopy for screening, surveillance, or a medically-indicated work-up at the University of Maryland Medical Center (main campus or Midtown)
• 3. Able to provide written informed consent prior to initiation of any study procedures
• 4. Healthy, as defined by considered fit to undergo outpatient elective EGD/colonoscopy by the evaluating health care provider

Exclusion Criteria:

• 1. Pregnancy or nursing mother
• 2. Known coagulopathy or bleeding disorder preventing mucosal biopsy
• 3. History of Crohn's disease or ulcerative colitis
• 4. For Subjects undergoing lower endoscopy (colonoscopy) only: Surgical removal of the ileocecal valve or any part of the small or large intestine (non-complicated appendectomy will be considered eligible)
• 5. Allergic reaction to oral typhoid or cholera vaccine in the past

• 6. Immunosuppression from illness or treatment, including

  1. immune-deficiency disorders such as Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)
  2. leukemia, lymphoma, or cancers (localized non-melanoma skin cancers which are deemed inactive should be considered eligible)
• 7. Receipt of any other vaccine two weeks prior to receipt of Ty21a or CVD 103-HgR
• 8. Positive urine pregnancy test (HCG) prior to colonoscopy or vaccination

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination, Endoscopy; Individuals receive immunization with Vivotif typhoid vaccine and/or Vaxchora cholera vaccine prior to routine endoscopic examination. During endoscopy, small bowel biopsies will be obtained to examine immune responses and microbiota at the mucosal level; brushings might also be obtained.	Drug: Vivotif Typhoid Oral Vaccine; The 4 doses (1 capsule each) will be administered on alternate days, e.g., days 0, 2, 4, and 7 (± 1 day) under the supervision of the study coordinator(s).; Other Names: Ty21a Typhoid Oral Vaccine; Drug: Vaxchora; One dose. Approximately 100 mL of cool or room temperature purified bottled water is placed into a clean disposable cup. The contents of the buffer sachet are added to the water and stirred. Then the contents of the active (lyophilized vaccine) sachet are added to the water and stirred for approximately 30 seconds. The reconstituted mixture should be completely ingested within 15 minutes.; Other Names: CVD 103-HgR
Experimental: Endoscopy, Vaccination, Endoscopy; Individuals receive immunization with Vivotif typhoid vaccine and/or Vaxchora cholera vaccine after initial endoscopic exam and specimen collection and prior to a routine follow up endoscopic examination during which additional specimens will be collected.	Drug: Vivotif Typhoid Oral Vaccine; The 4 doses (1 capsule each) will be administered on alternate days, e.g., days 0, 2, 4, and 7 (± 1 day) under the supervision of the study coordinator(s).; Other Names: Ty21a Typhoid Oral Vaccine; Drug: Vaxchora; One dose. Approximately 100 mL of cool or room temperature purified bottled water is placed into a clean disposable cup. The contents of the buffer sachet are added to the water and stirred. Then the contents of the active (lyophilized vaccine) sachet are added to the water and stirred for approximately 30 seconds. The reconstituted mixture should be completely ingested within 15 minutes.; Other Names: CVD 103-HgR
No Intervention: Endoscopy Without Vaccination; Individuals do not receive immunization but consent to collection of specimens during endoscopy. The specimens to be collected in all three groups include stool, saliva, and small bowel biopsies (terminal ileum if colonoscopy performed, duodenum if EGD performed).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders	Percentage of responders by cytokine production (Interferon-gamma (IFN-gamma) or Tumor Necrosis Factor-alpha (TNF-α)) by mass cytometry or flow cytometry. Responders will be defined as those volunteers showing increases post-immunization of >0.1% of positive CD8+ cells for IFN-gamma or TNF-α over baseline (pre-immunization) values.) or Tumor Necrosis Factor-alpha (TNF-α)) by mass cytometry or flow cytometry.	approximately 5 years

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2018
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Vibrio Infections; Salmonella Infections; Cholera; Typhoid Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: HP-00081568

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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