Induction of Gut Permeability by an Oral Vaccine

Sponsor

USDA, Western Human Nutrition Research Center (U.S. Fed)

Overall Status

Active, not recruiting

CT.gov ID

NCT04083950

Collaborator

(none)

Enrollment

Location

Arm

33.9

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Intestinal Permeability Inflammation Vaccine Typhoid Fever	Biological: Vivotif Typhoid Oral Vaccine Drug: Aspirin (Positive Control)	Early Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Induction of Gut Permeability by an Oral Vaccine

Actual Study Start Date :

Dec 4, 2019

Actual Primary Completion Date :

Jan 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single group All participants will receive the vaccine and aspirin.	Biological: 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. Other Names: Ty21a Typhoid Oral Vaccine Drug: Aspirin (Positive Control) Three tablets (325 mg aspirin in each tablet or 975 mg total) are swallowed on days 2 and 3. Other Names: Aspirin Challenge

Arm

Intervention/Treatment

Experimental: Single group

All participants will receive the vaccine and aspirin.

Biological: 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.

Other Names:

Ty21a Typhoid Oral Vaccine

Drug: Aspirin (Positive Control)

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

Other Names:

Aspirin Challenge

Outcome Measures

Primary Outcome Measures

Change in intestinal permeability [Day 1, 3, 16, 18, and 22]
Measurement of sugar (lactulose, D-mannitol, and sucralose) excretion in urine.

Secondary Outcome Measures

Antibody response to typhoid vaccination [Day 1, 18, 22, 24, and 29]
Measurement of Typhi-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) plasma cells in peripheral blood using the antibody in lymphocyte supernatant assay.
T-cell response to typhoid vaccination [Day 1, 22, and 29]
Measurement of vaccine-specific cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) T-cells in peripheral blood mononuclear cells.
Change in markers of inflammation [Day 1, 3, 16, 18, 22, and 24]
Measurement of plasma cytokines, chemokines, and acute phase proteins by a multiplex immunoassay.
Change in intestinal fatty acid binding protein (iFABP) [Day 1, 3, 16, 18, and 22]
Measurement of plasma iFABP.
Change in D-lactate [Day 1, 3, 16, 18, and 22]
Measurement of plasma D-lactate.
Change in diamine oxidase [Day 1, 3, 16, 18, and 22]
Measurement of plasma diamine oxidase.
Change in lipopolysaccharide binding protein (LBP) [Day 1, 3, 16, 18, and 22]
Measurement of plasma LBP.
Change in citrulline [Day 1, 3, 16, 18, and 22]
Measurement of plasma citrulline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 49 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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