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: October 20, 2021
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Bruce Greenwald, University of Maryland, Baltimore

Tracking Information

• First Submitted Date: May 29, 2019
• First Posted Date: May 31, 2019
• Last Update Posted Date: October 20, 2021
• Actual Study Start Date: October 24, 2013
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 29, 2019)

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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CVD 37000: Immunity and Microbiome Studies at Intestinal and Systemic Sites in Ty21a Vaccinated Adults
• Official Title: Not Provided

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

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

• Condition: Typhoid Vaccination

Intervention

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

Study Arms

• 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.
  Intervention: Drug: Vivotif 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.
  Intervention: Drug: Vivotif 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).

Publications *

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 18, 2021): 87
• Original Estimated Enrollment (submitted: May 29, 2019): 260
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03970304
• Other Study ID Numbers: HP-00056321
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Bruce Greenwald, University of Maryland, Baltimore
• Study Sponsor: University of Maryland, Baltimore
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Maryland, Baltimore
• Verification Date: October 2021