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Induction of Gut Permeability by an Oral Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04083950
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
USDA, Western Human Nutrition Research Center

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
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 : December 4, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

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 Name: 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 Name: Aspirin Challenge




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


Secondary Outcome Measures :
  1. Antibody response to typhoid vaccination [ Time Frame: 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.

  2. T-cell response to typhoid vaccination [ Time Frame: 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.

  3. Change in markers of inflammation [ Time Frame: Day 1, 3, 16, 18, 22, and 24 ]
    Measurement of plasma cytokines, chemokines, and acute phase proteins by a multiplex immunoassay.

  4. Change in intestinal fatty acid binding protein (iFABP) [ Time Frame: Day 1, 3, 16, 18, and 22 ]
    Measurement of plasma iFABP.

  5. Change in D-lactate [ Time Frame: Day 1, 3, 16, 18, and 22 ]
    Measurement of plasma D-lactate.

  6. Change in diamine oxidase [ Time Frame: Day 1, 3, 16, 18, and 22 ]
    Measurement of plasma diamine oxidase.

  7. Change in lipopolysaccharide binding protein (LBP) [ Time Frame: Day 1, 3, 16, 18, and 22 ]
    Measurement of plasma LBP.

  8. Change in citrulline [ Time Frame: Day 1, 3, 16, 18, and 22 ]
    Measurement of plasma citrulline.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083950


Contacts
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Contact: Ellen Bonnel, PhD 530-752-4184 ellen.bonnel@usda.gov
Contact: Yuriko Adkins, PhD 530-752-9469 yuriko.adkins@usda.gov

Locations
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United States, California
USDA, ARS, Western Human Nutrition Research Center Recruiting
Davis, California, United States, 95616
Contact: Ellen Bonnel, PhD    530-752-4184    ellen.bonnel@usda.gov   
Contact: Yuriko Adkins, PhD    530-752-9469    yuriko.adkins@usda.gov   
Sponsors and Collaborators
USDA, Western Human Nutrition Research Center
Investigators
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Principal Investigator: Danielle Lemay, PhD USDA, ARS, Western Human Nutrition Research Center

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Responsible Party: USDA, Western Human Nutrition Research Center
ClinicalTrials.gov Identifier: NCT04083950    
Other Study ID Numbers: FL109
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: December 6, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by USDA, Western Human Nutrition Research Center:
Gastrointestinal Health
Intestinal Permeability
Inflammation
Vaccine Response
Ty21a Typhoid Vaccine
Typhoid Fever
Additional relevant MeSH terms:
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Typhoid Fever
Inflammation
Pathologic Processes
Salmonella Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Aspirin
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics