Clinical trial NCT04083950: Induction of Gut Permeability by an Oral Vaccine
Official title: Induction of Gut Permeability by an Oral Vaccine
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Intestinal Permeability
Inflammation
Vaccine
Typhoid Fever
Keywords: Gastrointestinal Health
Intestinal Permeability
Inflammation
Vaccine Response
Ty21a Typhoid Vaccine
Typhoid Fever
Lead sponsor: USDA, Western Human Nutrition Research Center
Sponsor class: FED
First posted: 2019-09-10
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in intestinal permeability
timeFrame: Day 1, 3, 16, 18, and 22
Secondary outcomes:
measure: Antibody response to typhoid vaccination
timeFrame: Day 1, 18, 22, 24, and 29
measure: T-cell response to typhoid vaccination
timeFrame: Day 1, 22, and 29
measure: Change in markers of inflammation
timeFrame: Day 1, 3, 16, 18, 22, and 24
measure: Change in intestinal fatty acid binding protein (iFABP)
timeFrame: Day 1, 3, 16, 18, and 22
measure: Change in D-lactate
timeFrame: Day 1, 3, 16, 18, and 22
measure: Change in diamine oxidase
timeFrame: Day 1, 3, 16, 18, and 22
measure: Change in lipopolysaccharide binding protein (LBP)
timeFrame: Day 1, 3, 16, 18, and 22
measure: Change in citrulline
timeFrame: Day 1, 3, 16, 18, and 22
Other outcomes:
Locations:
city: Davis
country: United States
facility: USDA, ARS, Western Human Nutrition Research Center
state: California
Study officials:
affiliation: USDA, ARS, Western Human Nutrition Research Center
name: Danielle Lemay, PhD
role: PRINCIPAL_INVESTIGATOR
References: