Induction of Gut Permeability by an Oral Vaccine
试验速览
- 阶段
- 早期 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change in intestinal permeability
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Body Mass Index (BMI) 18.5 - 29.9 kg/m2
排除标准
- •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
研究组 & 干预措施
Single group
All participants will receive the vaccine and aspirin.
干预措施: Vivotif Typhoid Oral Vaccine (Biological)
Single group
All participants will receive the vaccine and aspirin.
干预措施: Aspirin (Positive Control) (Drug)
结局指标
主要结局
Change in intestinal permeability
时间窗: Day 1, 3, 16, 18, and 22
Measurement of sugar (lactulose, D-mannitol, and sucralose) excretion in urine.
次要结局
- Change in citrulline(Day 1, 3, 16, 18, and 22)
- T-cell response to typhoid vaccination(Day 1, 22, and 29)
- Change in markers of inflammation(Day 1, 3, 16, 18, 22, and 24)
- Change in intestinal fatty acid binding protein (iFABP)(Day 1, 3, 16, 18, and 22)
- Antibody response to typhoid vaccination(Day 1, 18, 22, 24, and 29)
- Change in D-lactate(Day 1, 3, 16, 18, and 22)
- Change in diamine oxidase(Day 1, 3, 16, 18, and 22)
- Change in lipopolysaccharide binding protein (LBP)(Day 1, 3, 16, 18, and 22)