Induction of Gut Permeability by an Oral Vaccine

NCT ID: NCT04083950

Last Updated: 2025-11-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-04
• Study Completion Date: 2026-09-30

Brief Summary

This study evaluates the effect of an oral typhoid vaccine on disruption of the intestinal barrier and response of the immune system. Intestinal and whole-body responses will be measured in all participants before and after the vaccine.

Detailed Description

The licensed Ty21a vaccine strain of S. enterica Typhi is routinely used by travelers to countries where typhoid is common. It is not known whether the vaccine causes measurable changes in intestinal permeability and whether changes in permeability are correlated with the magnitude of the vaccine response. In the current study, gut permeability will be measured in participants at baseline and after an aspirin challenge, which is known to disrupt intestinal permeability, and after the first, second, and fourth doses of a the Ty21a vaccine. Intestinal permeability will be measured using a three-sugar absorption test composed of lactulose, mannitol, and sucralose and by several plasma markers. Vaccine response will be measured by quantitating T cells and newly developed IgG-or IgA-secreting plasma cells specific for Ty21a.

Conditions

Intestinal Permeability; Inflammation; Vaccine; Typhoid Fever

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Single group

All participants will receive the vaccine and aspirin.

Group Type: EXPERIMENTAL

Vivotif Typhoid Oral Vaccine

Intervention Type: BIOLOGICAL

One capsule is swallowed on alternate days, e.g. days 15, 17, 19, and 21, for a total of 4 capsules.

Aspirin (Positive Control)

Intervention Type: DRUG

Three tablets (325 mg aspirin in each tablet or 975 mg total) are swallowed on days 2 and 3.

Interventions

Vivotif Typhoid Oral Vaccine

One capsule is swallowed on alternate days, e.g. days 15, 17, 19, and 21, for a total of 4 capsules.

Intervention Type: BIOLOGICAL

Aspirin (Positive Control)

Three tablets (325 mg aspirin in each tablet or 975 mg total) are swallowed on days 2 and 3.

Intervention Type: DRUG

Other Intervention Names

Ty21a Typhoid Oral Vaccine; Aspirin Challenge

Eligibility Criteria

Inclusion Criteria

• Body Mass Index (BMI) 18.5 - 29.9 kg/m2

Exclusion Criteria

• Has HIV/AIDS or another disease that affects the immune system
• Has any kind of cancer
• Decline to take an HIV blood test
• Blood pressure greater than or equal to 140/90 mmhg
• Pregnant or lactating women
• Refusal to take a pregnancy test prior to the study
• Refusal to use a method of birth control during the study
• Allergy to vaccine components, i.e. Thimerosal and enteric-coated capsules
• Allergy to oral typhoid vaccine
• Allergy to aspirin
• Daily use of blood thinners
• Use of anti-inflammatory medications, i.e. nonsteroidal anti-inflammatory drugs (NSAID), aspirin, 3 or more times per month
• Use of sulfonamides or antibiotics in the past 30 days
• Use of anti-hypertensive drugs, i.e. beta blockers, diuretics, calcium channel blockers
• Use of anti-malaria drugs, i.e. Mefloquine, chloroquine, and proguanil
• Use of drugs that affect the immune system, i.e. immunosuppressants, immune-modifying drugs, corticosteroids, i.e. cortisone, prednisone, methylprednisolone, for 2 weeks or longer
• Is taking cancer treatment with radiation or drugs
• Greater than ten years residence in a typhoid-endemic area
• Receipt of typhoid vaccine in the last 5 years
• Receipt of any vaccine two weeks prior to receipt of Ty21a vaccine
• Individuals at increased risk of developing complications from a live, bacterial vaccine
• History of typhoid fever
• History of primary immune deficiency or autoimmune disease
• History of acute or chronic gastrointestinal (GI) disorder, i.e. Crohn's disease, irritable bowel syndrome, gastric ulcer
• Diarrheal illness (defined as passing 3 or more abnormally loose or watery stool in a 24 hour period) or persistent vomiting 2 weeks prior to the study
• History of bleeding disorder, including bleeding from the GI tract
• History of chronic illnesses, i.e. diabetes, cardiovascular disease, cancer, gastrointestinal malabsorption or inflammatory diseases, kidney disease, autoimmune disorders, HIV, liver disease, including hepatitis B and C.
• Asthma if taking medication on a daily basis
• Recent surgery (within 3 months)
• History of GI surgery
• Recent hospitalization (within 3 months)
• Acute febrile illness (within 2 weeks)
• Unwillingness to discontinue consumption of artificial sweeteners in foods or drinks, i.e. sport drinks, coconut water, "diet" drinks and foods (possibly containing sucralose)
• Not having at least one arm vein suitable for blood drawing
• Unwilling or uncomfortable with blood draws seven times in 29 days
• Regular blood or blood product donation and refusal to suspend donation
• Current participation in another research study
• Unable to fast for 12-16 hours

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

USDA, Western Human Nutrition Research Center

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Danielle Lemay, PhD

Role: PRINCIPAL_INVESTIGATOR

USDA, ARS, Western Human Nutrition Research Center

Locations

USDA, ARS, Western Human Nutrition Research Center

Davis, California, United States

Countries

United States

Other Identifiers

FL109

Identifier Type: -

Identifier Source: org_study_id