Induction of Gut Permeability by an Oral Vaccine

Inflammation Clinical Trial

Official title:

Induction of Gut Permeability by an Oral Vaccine

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04083950
• Other study ID #: FL109
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: December 4, 2019
• Est. completion date: September 30, 2024

Study information

• Verified date: January 2024
• Source: USDA, Western Human Nutrition Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: September 30, 2024
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammation
• Intestinal Permeability
• Typhoid Fever
• Vaccine

Intervention

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.

Drug:
• Aspirin (Positive Control)
Three tablets (325 mg aspirin in each tablet or 975 mg total) are swallowed on days 2 and 3.

Locations

Country	Name	City	State
United States	USDA, ARS, Western Human Nutrition Research Center	Davis	California

Sponsors (1)

Lead Sponsor	Collaborator
USDA, Western Human Nutrition Research Center

Country where clinical trial is conducted

United States, 

Outcome

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