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

• ClinicalTrials.gov Identifier: NCT03705585
• Recruitment Status: Recruiting
• First Posted: October 15, 2018
• Last Update Posted: April 14, 2021
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Bruce Greenwald, University of Maryland, Baltimore

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Typhoid and/or Cholera Vaccination	Drug: Vivotif Typhoid Oral Vaccine; Drug: Vaxchora	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Volunteers who choose to take part in this study will receive the licensed FDA approved Oral Typhoid Vaccine (Vivotif) and/or the licensed FDA approved Oral Cholera Vaccine (Vaxchora). Volunteers also have the possibility of being a control participant who will not be vaccinated.
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: CVD 38000: Immunity, Microbiome, Epigenetics, and a Systems Biology Approach to the Study of Responses to Vaccination With Typhoid and/or Cholera
• Actual Study Start Date: November 5, 2018
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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).

Outcome Measures

Primary Outcome Measures :

1. Percentage of Responders [ Time Frame: approximately 5 years ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Robin Barnes, CRNP; 410-706-6156; rbarnes@som.umaryland.edu

Locations

United States, Maryland

University of Maryland, Baltimore, Center for Vaccine Development and Global Health; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Robin Barnes, CRNP

Sponsors and Collaborators

University of Maryland, Baltimore

More Information

• Responsible Party: Bruce Greenwald, Professor of Medicine, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03705585
• Other Study ID Numbers: HP-00081568
• First Posted: October 15, 2018
• Last Update Posted: April 14, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Cholera; Typhoid Fever; Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Salmonella Infections; Enterobacteriaceae Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs