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WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study

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: NCT04543877
Recruitment Status : Not yet recruiting
First Posted : September 10, 2020
Last Update Posted : March 2, 2022
Sponsor:
Collaborator:
University of Minnesota
Information provided by (Responsible Party):
USDA, Western Human Nutrition Research Center

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.

Condition or disease Intervention/treatment Phase
Inflammation Vaccine Intestinal Permeability Typhoid Fever Dietary Supplement: Inulin Dietary Supplement: Maltodextrin Biological: Ty21a Typhoid Fever Vaccine Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study
Estimated Study Start Date : June 1, 2022
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Inulin

Arm Intervention/treatment
Experimental: 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.
Dietary Supplement: Inulin
Consume 12 grams/day of inulin for 5 weeks (Day 9 - 43).
Other Name: Orafti GR

Biological: Ty21a Typhoid Fever Vaccine
All participants will receive the vaccine. One capsule is swallowed on alternate days, e.g. days 30, 32, 34, and 36 for a total of 4 capsules.
Other Name: Vivotif

Placebo Comparator: 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.
Dietary Supplement: Maltodextrin
Consume 12 grams/day of maltodextrin for 5 weeks (Day 9 - 43).
Other Name: Maltrin M100

Biological: Ty21a Typhoid Fever Vaccine
All participants will receive the vaccine. One capsule is swallowed on alternate days, e.g. days 30, 32, 34, and 36 for a total of 4 capsules.
Other Name: Vivotif




Primary Outcome Measures :
  1. Change in whole blood antibody response to typhoid vaccination [ Time Frame: Day 26, 37, and 39 ]
    Measurement of baseline level (Day 26; before first vaccine dose) and change of vaccine-specific antibody response using the antibody-in-lymphocyte-supernatant (ALS) assay to identify nascent antibody-secreting cells in blood.

  2. Change in plasma antibody response to typhoid vaccination [ Time Frame: Day 26 and 58 ]
    Measurement of baseline level (Day 26; before first vaccine dose) and change in plasma antibody levels

  3. Change in fecal antibody levels from typhoid vaccination [ Time Frame: Day 26, 39, and 58 ]
    Measurement of baseline level (Day 26; before first vaccine dose) and change in fecal antibody levels


Secondary Outcome Measures :
  1. Change in plasma cytokines as markers of systemic inflammation [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of plasma cytokines interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), IL-1beta using an enzyme-linked immunoassay (ELISA)

  2. Change in plasma chemokines [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of plasma chemokines including IL-8, Interferon-inducible protein 10 (IP-10) and Granulocyte-macrophage colony stimulating factor (GM-CSF) will be measured by ELISA.

  3. Change in plasma acute phase proteins [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of acute phase reactants C reactive protein (CRP) and serum amyloid-A (SAA) measured by ELISA.

  4. Change in plasma adhesion molecules [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of plasma intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1) measured by ELISA.

  5. Change in plasma myeloperoxidase [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of myeloperoxidase in plasma using an ELISA.

  6. Change in plasma neopterin [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of neopterin in plasma using an ELISA.

  7. Change in a plasma marker of lipopolysaccharide (LPS) exposure [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Measurement of plasma LPS-binding protein using an ELISA.

  8. Change in blood monocyte subsets [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Monocyte subsets will be analyzed using flow cytometry.

  9. Change in plasma short chain fatty acids (SCFA) [ Time Frame: Day 8, 26, 37, 39, and 58 ]
    Blood SCFA will be measured using GC-MS.

  10. Change in urinary lactulose [ Time Frame: Day 8, 26, and 37 ]
    Measurement of lactulose, a synthetic sugar and an indicator of intestinal permeability, in urine by gas chromatography mass-spectrometry (GC-MS).

  11. Change in urinary D-mannitol [ Time Frame: Day 8, 26, and 37 ]
    Measurement of D-mannitol, a sugar alcohol and an indicator of intestinal permeability, in urine by GC-MS.

  12. Changes in dietary intake [ Time Frame: Period 1: Days 1-7; Period 2: Days 16-25; Period 3: Days 58-65 ]
    Three non-consecutive 24-hour dietary recalls will be collected per period. A 3-day average of nutrient intake will be calculated per period.

  13. Change in fecal microbiome identity [ Time Frame: 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 ]
    Measurement of relative abundance of colonic bacteria using polymerase chain reaction (PCR) amplification and sequencing of the 16S ribosomal ribonucleic acid (RNA) will be performed using DNA isolated from stool. Stools will be collected 3 times per period.

  14. Change in fecal microbiome function [ Time Frame: 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 ]
    Total RNA, and specifically, mucin-2 messenger ribonucleic acid (mRNA), will be analyzed from preserved stools. Stools will be collected 3 times per period.

  15. Change in stool consistency [ Time Frame: 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 ]
    Measurement of stool consistency using the Bristol stool scale, a medical tool used to classify stool forms into 7 categories. Stools will be collected 3 times per period.

  16. Change in fecal pH [ Time Frame: 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 ]
    Measurement of fecal pH using a standard pH meter. Stools will be collected 3 times per period.

  17. Change in fecal calprotectin [ Time Frame: 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 ]
    Measurement of calprotectin will be done by ELISA. Stools will be collected 3 times per period.

  18. Change in fecal secretory immunoglobulin A (sIgA) [ Time Frame: 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 ]
    Measurement of sIgA using ELISA. Stools will be collected 3 times per period.

  19. Change in fecal SCFA [ Time Frame: 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 ]
    Measurement of SCFA will be done by GC-MS. Stools will be collected 3 times per period.

  20. Change in fecal bile acids [ Time Frame: 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 ]
    Measurement of bile acids will be done by GC-MS. Stools will be collected 3 times per period.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
    • Males 18 - 30 years old, less than 34 g/day
    • Males 31 - 50 years old, less than 31 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

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): NCT04543877


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
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
University of Minnesota
Investigators
Layout table for investigator information
Principal Investigator: Danielle Lemay, PhD USDA, ARS, Western Human Nutrition Research Center
Principal Investigator: Charles Stephensen, PhD USDA, ARS, Western Human Nutrition Research Center
Principal Investigator: Mary Kable, PhD USDA, ARS, Western Human Nutrition Research Center
Publications:

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Responsible Party: USDA, Western Human Nutrition Research Center
ClinicalTrials.gov Identifier: NCT04543877    
Other Study ID Numbers: FL113
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by USDA, Western Human Nutrition Research Center:
Gastrointestinal Health
Intestinal Permeability
Vaccine Response
Inflammation
Ty21a Typhoid Vaccine
Typhoid Fever
Microbiome
Bifidobacterium
Additional relevant MeSH terms:
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Typhoid Fever
Inflammation
Pathologic Processes
Salmonella Infections
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections