CVD 37000: Immunity and Microbiome Studies at Intestinal and Systemic Sites in Ty21a Vaccinated Adults

• ClinicalTrials.gov Identifier: NCT03970304
• Recruitment Status: Active, not recruiting
• First Posted: May 31, 2019
• Last Update Posted: November 14, 2022
• 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 affect the normal immune system and bacteria in the intestine. Patients having standard-of-care colonoscopies will be divided into 3 groups:

Group 1: Vivotif typhoid vaccination then colonoscopy; Group 2: Colonoscopy, then Vivotif typhoid vaccination, then follow-up colonoscopy; Group 3: Colonoscopy without vaccination.

The Vivotif typhoid vaccine used in this study is 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 vaccine.

Condition or disease	Intervention/treatment	Phase
Typhoid Vaccination	Drug: Vivotif Typhoid Oral Vaccine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 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). Volunteers also have the possibility of being a control participant who will not be vaccinated.
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Actual Study Start Date: October 24, 2013
• Estimated Primary Completion Date: June 30, 2024
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vaccination, Colonoscopy; Individuals receive immunization with Vivotif typhoid vaccine prior to routine colonoscopy examination. During colonoscopy, small bowel biopsies will be obtained to examine immune responses and microbiota at the mucosal level; brushings will 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
Experimental: Colonoscopy, Vacciniation, Colonoscopy; Individuals receive immunization with Vivotif typhoid vaccine after initial colonoscopy exam and specimen collection and prior to a routine follow up colonoscopy 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
No Intervention: Colonoscopy Without Vaccination; Individuals do not receive immunization but consent to collection of specimens during colonoscopy. The specimens to be collected in all three groups include stool, saliva, and small bowel biopsies (terminal ileum).

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:

• Age 18 years and older
• Undergoing colonoscopy for screening or surveillance for colorectal cancer at the University of Maryland
• Provide written informed consent prior to initiation of any study procedures
• Healthy, as defined by considered fit to undergo outpatient elective colonoscopy by the referring health care provider

Exclusion Criteria:

• Pregnancy or nursing mother
• Known coagulopathy or bleeding disorder preventing mucosal biopsy
• History of Crohn's disease or ulcerative colitis
• Surgical removal of the ileocecal valve or any part of the small or large intestine
• Allergic reaction to oral typhoid vaccine in the past

• Immunosuppression from illness or treatment, including

  • immune-deficiency disorders such as Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS)
  • leukemia, lymphoma, or cancers
  • immune suppressive medications or treatments, such as corticosteroids or radiation
• Receipt of any other vaccine two weeks prior to receipt of Ty21a
• Positive urine pregnancy test (HCG) prior to colonoscopy or vaccination

Contacts and Locations

Locations

United States, Maryland

Universtiy of Maryland, Baltimore, Center for Vaccine Development and Global Health

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Booth JS, Goldberg E, Patil SA, Barnes RS, Greenwald BD, Sztein MB. Age-dependency of terminal ileum tissue resident memory T cell responsiveness profiles to S. Typhi following oral Ty21a immunization in humans. Immun Ageing. 2021 Apr 19;18(1):19. doi: 10.1186/s12979-021-00227-y.

Booth JS, Goldberg E, Barnes RS, Greenwald BD, Sztein MB. Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments. J Transl Med. 2020 Feb 25;18(1):102. doi: 10.1186/s12967-020-02263-6.

• Responsible Party: Bruce Greenwald, Professor of Medicine, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03970304
• Other Study ID Numbers: HP-00056321
• First Posted: May 31, 2019
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

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

Additional relevant MeSH terms:

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