Inflammation Clinical Trial
Official title:
WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study
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.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | September 30, 2025 |
Est. primary completion date | September 30, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 50 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | USDA, ARS, Western Human Nutrition Research Center | Davis | California |
Lead Sponsor | Collaborator |
---|---|
USDA, Western Human Nutrition Research Center | University of Minnesota |
United States,
Costabile A, Kolida S, Klinder A, Gietl E, Bauerlein M, Frohberg C, Landschutze V, Gibson GR. A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects. Br J Nutr. 2010 Oct;104(7):1007-17. doi: 10.1017/S0007114510001571. Epub 2010 Jul 1. — View Citation
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Micka A, Siepelmeyer A, Holz A, Theis S, Schon C. Effect of consumption of chicory inulin on bowel function in healthy subjects with constipation: a randomized, double-blind, placebo-controlled trial. Int J Food Sci Nutr. 2017 Feb;68(1):82-89. doi: 10.1080/09637486.2016.1212819. Epub 2016 Aug 5. — View Citation
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* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in vaccine-specific antibody-secreting cell response to oral Ty21a typhoid vaccination using the standard 4-dose regimen | 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. | Day 26, 37, and 39 | |
Secondary | Change in vaccine-specific serum antibody response to typhoid vaccination | Measurement of baseline level (Day 26; before first vaccine dose) and post-vaccine (28 d after first vaccine dose) antibody levels (IgG, IgM, IgA) | Day 26 and 58 | |
Secondary | Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination | Measurement of baseline level (Day 26; before first vaccination dose) and change in fecal antibody levels | Day 26, 39, and 58 | |
Secondary | Change in plasma cytokines as markers of systemic inflammation | Measurement of plasma cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and IL-1beta | Day 8, 26, 37, 39, and 58 | |
Secondary | Change in plasma acute phase proteins and adhesion molecules | Measurement of acute phase reactants, such as C-reactive protein (CRP) and serum amyloid-A (SAA), and intercellular adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial cell adhesion molecule-1 (VCAM-1) | Day 8, 26, 37, 39, and 58 | |
Secondary | Change in a plasma marker of lipopolysaccharide (LPS) exposure | Measurement of plasma LPS-binding protein using an ELISA. | Day 8, 26, 37, 39, and 58 | |
Secondary | Change in blood monocyte subsets | Monocyte subsets will be analyzed using flow cytometry. | Day 8, 26, 37, 39, and 58 | |
Secondary | Change in plasma short chain fatty acids (SCFA) | Plasma SCFA will be measured using liquid chromatography-mass spectrometry (LC-MS). | Day 8, 26, 37, 39, and 58 | |
Secondary | Change in urinary lactulose and D-mannitol | Measurement of lactulose to mannitol ratio, an indicator of intestinal permeability, in urine | Day 8, 26, and 37 | |
Secondary | Change in fecal microbiome | Measurement of relative abundance of colonic bacteria using DNA isolated from stool. | 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 | |
Secondary | Change in fecal mRNA | Total RNA, and specifically, messenger ribonucleic acid (mRNA), will be analyzed from preserved stools. | 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 | |
Secondary | Change in stool consistency and frequency | Measurement of stool consistency using the Bristol stool scale, a medical tool used to classify stool forms into 7 categories, and frequency via self-report in diaries. | 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 | |
Secondary | Change in GI symptoms | Measurement of GI symptoms using a 10-symptom health questionnaire with degree of discomfort ranked in one of four categories (0 absent, 1 mild, 2 moderate, or 3 severe; PMID: 9301412) | 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 | |
Secondary | Change in fecal pH | Measurement of fecal pH using a standard pH meter. | 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 | |
Secondary | Change in fecal calprotectin | Measurement of calprotectin will be done by ELISA | 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 | |
Secondary | Change in fecal SCFA | Measurement of SCFA will be done by gas chromatography-mass spectrometry (GC-MS.) | 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 | |
Secondary | Change in fecal metabolites | Measurement of bile acids and other metabolites will be measured | 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 | |
Secondary | Change in fecal secretory total immunoglobulin A (sIgA) | Measurement of total fecal sIgA using ELISA. | 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 |
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