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

NCT03970304 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: HP-00056321
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

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.

Conditions

Typhoid Vaccination

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

Vaccination, Colonoscopy

EXPERIMENTAL

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

Colonoscopy, Vacciniation, Colonoscopy

EXPERIMENTAL

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

Colonoscopy Without Vaccination

NO INTERVENTION

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).

Interventions

Vivotif Typhoid Oral Vaccine DRUG

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).

Also known as: Ty21a Typhoid Oral Vaccine

Colonoscopy, Vacciniation, Colonoscopy; Vaccination, Colonoscopy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

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

Baltimore, Maryland, 21201, United States

Location

Related Publications (2)

• 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.

  PMID: 33874975 DERIVED

• 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.

  PMID: 32098623 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: May 31, 2019
• Study Start: October 24, 2013
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)