WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in vaccine-specific antibody-secreting cell response to oral Ty21a typhoid vaccination using the standard 4-dose regimen
研究概览
简要总结
The purpose of this study is to determine if adding dietary fiber, such as inulin, to a diet that does not have enough fiber would raise the levels of potentially beneficial bacteria, such as Bifidobacterium, in the gut. There is evidence to suggest that these microbes can affect gut health and immune response, including to vaccines. The investigators will examine how inulin in the diet (compared to the maltodextrin control) (1) causes changes in the composition and function of the gut microbes, (2) reduces gut inflammation and gut leakiness caused by the vaccine, (3) increases immune response to vaccination, and (4) changes the expression of important adhesion molecules on the surface of white blood cells. Intestinal and whole-body responses will be measured in all participants.
详细描述
Inulin, a dietary fiber supplement, is known to increase gut levels of potentially beneficial bacteria, including Bifidobacterium that are indigenous to gut microbiomes. Our underlying hypothesis is that the commensal microbiome, including Bifidobacterium, in the proximal colon or distal ileum affects the environment of draining lymph nodes and can thus modulate immune responses, including to vaccines. In the current study, participants will consume 12 grams/day inulin or maltodextrin (control) for 3 weeks before the administration of the Ty21a typhoid fever vaccine, 1 week during the vaccine, and 1 week after the vaccine. Vaccine response will be measured by counting T cells and immunoglobulin G (IgG) or immunoglobulin A (IgA)-secreting plasma cells specific for Ty21a. Gut permeability will be measured at baseline, and before and after the vaccine administration. Systemic inflammation and immune activation will be measured by analyzing blood for markers of inflammation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body Mass Index (BMI) 18.5 - 30.9 kg/m2
- •inadequate total dietary fiber intake defined as:
- •Females 18 - 30 years old, less than 28 g/day
- •Females 31 - 50 years old, less than 25 g/day
- •Females 51+ year old, less than 22 g/day
- •Males 18 - 30 years old, less than 34 g/day
- •Males 31 - 50 years old, less than 31 g/day
- •Males 51+ years old, less than 28 g/day
排除标准
- •blood pressure greater than or equal to 140/90 mmHg
- •has HIV/AIDS or another disease that affects the immune system
- •has any kind of cancer
- •inability to lift 30 pounds with assistance (for transporting refrigerated stool containers)
- •decline to take an HIV blood test
- •pregnant or lactating women
- •refusal to take a pregnancy test
- •female subjects: refusal to use a method of birth control 1 week prior to the administration of the vaccine, 1 week during the vaccine, and 1 week after the vaccine
- •allergy to vaccine components, i.e. thimerosal and enteric-coated capsules
- •allergy to oral typhoid vaccine
- •use of anti-inflammatory medications, i.e. nonsteroidal anti-inflammatory drugs (NSAID), aspirin, 3 or more times per month
- •use of sulfonamides or antibiotics 3 months prior to the receipt of Ty21a vaccine.
- •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 affects the immune system, i.e. immunosuppressants, immune-modifying drugs, corticosteroids, i.e. cortisone, prednisone, methylprednisolone, for 2 weeks or longer
- •use of biologics, i.e. Lantus, Remicade, Rituxan, Humira, Herceptin, Avastin, Lucentis, Enbrel for 2 weeks or longer
- •undergoing cancer treatment with radiation or drugs
- •greater than 10 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 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)
- •fever (within 2 weeks)
- •unwillingness to discontinue probiotic, prebiotic, or other supplements (except Recommended Dietary Allowance-level vitamin and mineral supplements), fiber supplements, or food and beverage products containing inulin, chicory root fiber, or maltodextrin during the study
- •not having at least one arm vein suitable for blood drawing
- •unwilling or uncomfortable with blood draws and stool collections
- •regular blood or blood product donation and refusal to suspend donation
- •current participation in another research study
- •unable to fast for 12-16 hours
- •have fewer than 3 bowel movements per week
- •consuming one or more servings of added-inulin foods per day over the past month
研究组 & 干预措施
Inulin and Ty21a Vaccine
Participants will consume 12 grams/day of inulin for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.
干预措施: Inulin (Dietary Supplement)
Inulin and Ty21a Vaccine
Participants will consume 12 grams/day of inulin for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.
干预措施: Ty21a Typhoid Fever Vaccine (Biological)
Maltodextrin and Ty21a Vaccine
Participants will consume 12 grams/day of maltodextrin (control) for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.
干预措施: Maltodextrin (Dietary Supplement)
Maltodextrin and Ty21a Vaccine
Participants will consume 12 grams/day of maltodextrin (control) for 3 weeks before the administration of the Ty21a vaccine, 1 week during the vaccine, and 1 week after the vaccine for a total of 5 weeks.
干预措施: Ty21a Typhoid Fever Vaccine (Biological)
结局指标
主要结局
Change in vaccine-specific antibody-secreting cell response to oral Ty21a typhoid vaccination using the standard 4-dose regimen
时间窗: Day 26, 37, and 39
Measurement of baseline level (Day 26; before first vaccine dose) and post-vaccine, antibody response, Immunoglobulin G (IgG), Immunoglobulin M (IgM) and IgA, 7 and 9 days after the first vaccine dose using the antibody-in-lymphocyte-supernatant (ALS) assay to identify antibody-secreting cells in blood. Two antigens will be used: Ty21a outer membrane protein and lipopolysaccharide from Salmonella Typhi.
次要结局
- Change in a plasma marker of lipopolysaccharide (LPS) exposure(Day 8, 26, 37, 39, and 58)
- Change in fecal secretory total immunoglobulin A (sIgA)(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination(Day 26, 39, and 58)
- Change in GI symptoms(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in blood monocyte subsets(Day 8, 26, 37, 39, and 58)
- Change in urinary lactulose and D-mannitol(Day 8, 26, and 37)
- Change in fecal mRNA(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in plasma acute phase proteins and adhesion molecules(Day 8, 26, 37, 39, and 58)
- Change in fecal pH(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in vaccine-specific serum antibody response to typhoid vaccination(Day 26 and 58)
- Change in plasma cytokines as markers of systemic inflammation(Day 8, 26, 37, 39, and 58)
- Change in fecal microbiome(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in stool consistency and frequency(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in fecal SCFA(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in plasma short chain fatty acids (SCFA)(Day 8, 26, 37, 39, and 58)
- Change in fecal calprotectin(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)
- Change in fecal metabolites(Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 26-36; Period 4: Days 37-43; Period 5: Days 58-65)