Clinical trial NCT04543877: WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study
Official title: WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Inflammation
Vaccine
Intestinal Permeability
Typhoid Fever
Keywords: Gastrointestinal Health
Intestinal Permeability
Vaccine Response
Inflammation
Ty21a Typhoid Vaccine
Typhoid Fever
Microbiome
Bifidobacterium
Lead sponsor: USDA, Western Human Nutrition Research Center
Sponsor class: FED
Collaborators: name: University of Minnesota
First posted: 2020-09-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Body Mass Index (BMI) 18.5 - 30.9 kg/m2
2. 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

Exclusion Criteria:

1. blood pressure greater than or equal to 140/90 mmHg
2. has HIV/AIDS or another disease that affects the immune system
3. has any kind of cancer
4. inability to lift 30 pounds with assistance (for transporting refrigerated stool containers)
5. decline to take an HIV blood test
6. pregnant or lactating women
7. refusal to take a pregnancy test
8. 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
9. allergy to vaccine components, i.e. thimerosal and enteric-coated capsules
10. allergy to oral typhoid vaccine
11. use of anti-inflammatory medications, i.e. nonsteroidal anti-inflammatory drugs (NSAID), aspirin, 3 or more times per month
12. use of sulfonamides or antibiotics 3 months prior to the receipt of Ty21a vaccine.
13. use of anti-hypertensive drugs, i.e. beta blockers, diuretics, calcium channel blockers
14. use of anti-malaria drugs, i.e. mefloquine, chloroquine, and proguanil
15. 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
16. use of biologics, i.e. Lantus, Remicade, Rituxan, Humira, Herceptin, Avastin, Lucentis, Enbrel for 2 weeks or longer
17. undergoing cancer treatment with radiation or drugs
18. greater than 10 years residence in a typhoid-endemic area
19. receipt of typhoid vaccine in the last 5 years
20. receipt of any vaccine two weeks prior to receipt of Ty21a vaccine
21. individuals at increased risk of developing complications from a live, bacterial vaccine
22. history of typhoid fever
23. history of primary immune deficiency or autoimmune disease
24. history of acute or chronic gastrointestinal (GI) disorder, i.e. Crohn's disease, irritable bowel syndrome, gastric ulcer
25. 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
26. 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
27. asthma if taking medication on a daily basis
28. recent surgery (within 3 months)
29. history of GI surgery
30. recent hospitalization (within 3 months)
31. fever (within 2 weeks)
32. 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
33. not having at least one arm vein suitable for blood drawing
34. unwilling or uncomfortable with blood draws and stool collections
35. regular blood or blood product donation and refusal to suspend donation
36. current participation in another research study
37. unable to fast for 12-16 hours
38. have fewer than 3 bowel movements per week
39. consuming one or more servings of added-inulin foods per day over the past month

Primary outcomes:
measure: Change in vaccine-specific antibody-secreting cell response to oral Ty21a typhoid vaccination using the standard 4-dose regimen
timeFrame: Day 26, 37, and 39
Secondary outcomes:
measure: Change in vaccine-specific serum antibody response to typhoid vaccination
timeFrame: Day 26 and 58
measure: Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination
timeFrame: Day 26, 39, and 58
measure: Change in plasma cytokines as markers of systemic inflammation
timeFrame: Day 8, 26, 37, 39, and 58
measure: Change in plasma acute phase proteins and adhesion molecules
timeFrame: Day 8, 26, 37, 39, and 58
measure: Change in a plasma marker of lipopolysaccharide (LPS) exposure
timeFrame: Day 8, 26, 37, 39, and 58
measure: Change in blood monocyte subsets
timeFrame: Day 8, 26, 37, 39, and 58
measure: Change in plasma short chain fatty acids (SCFA)
timeFrame: Day 8, 26, 37, 39, and 58
measure: Change in urinary lactulose and D-mannitol
timeFrame: Day 8, 26, and 37
measure: Change in fecal microbiome
timeFrame: 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
measure: Change in fecal mRNA
timeFrame: 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
measure: Change in stool consistency and frequency
timeFrame: 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
measure: Change in GI symptoms
timeFrame: 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
measure: Change in fecal pH
timeFrame: 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
measure: Change in fecal calprotectin
timeFrame: 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
measure: Change in fecal SCFA
timeFrame: 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
measure: Change in fecal metabolites
timeFrame: 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
measure: Change in fecal secretory total immunoglobulin A (sIgA)
timeFrame: 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
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
affiliation: USDA, ARS, Western Human Nutrition Research Center
name: Ryan Snodgrass, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: USDA, ARS, Western Human Nutrition Research Center
name: Mary Kable, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: USDA, ARS, Western Human Nutrition Research Center
name: Bess Caswell, PhD
role: PRINCIPAL_INVESTIGATOR
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