WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study

NCT04543877 | Completed Early Phase 1 FDA Drug

• 1 other identifier: FL113
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Inflammation; Vaccine; Intestinal Permeability; Typhoid Fever

Keywords

Gastrointestinal Health; Intestinal Permeability; Vaccine Response; Inflammation; Ty21a Typhoid Vaccine; Typhoid Fever; Microbiome; Bifidobacterium

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• Change in vaccine-specific serum antibody response to typhoid vaccination

  Day 26 and 58

• Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination

  Day 26, 39, and 58

• Change in plasma cytokines as markers of systemic inflammation

  Day 8, 26, 37, 39, and 58

• Change in plasma acute phase proteins and adhesion molecules

  Day 8, 26, 37, 39, and 58

• Change in a plasma marker of lipopolysaccharide (LPS) exposure

  Day 8, 26, 37, 39, and 58

Study Arms (2)

Inulin and Ty21a Vaccine

EXPERIMENTAL

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; Biological: Ty21a Typhoid Fever Vaccine

Maltodextrin and Ty21a Vaccine

PLACEBO COMPARATOR

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; Biological: Ty21a Typhoid Fever Vaccine

Interventions

Ty21a Typhoid Fever Vaccine BIOLOGICAL

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.

Also known as: Vivotif

Inulin and Ty21a Vaccine; Maltodextrin and Ty21a Vaccine

Inulin DIETARY_SUPPLEMENT

Consume 12 grams/day of inulin for 5 weeks (Day 9 - 43).

Also known as: Orafti GR

Inulin and Ty21a Vaccine

Maltodextrin DIETARY_SUPPLEMENT

Consume 12 grams/day of maltodextrin for 5 weeks (Day 9 - 43).

Also known as: Maltrin M100

Maltodextrin and Ty21a Vaccine

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• USDA, Western Human Nutrition Research Center: lead
• University of Minnesota: collaborator

Study Sites (1)

USDA, ARS, Western Human Nutrition Research Center

Davis, California, 95616, United States

Location

Related Publications (13)

• Meyer D, Stasse-Wolthuis M. The bifidogenic effect of inulin and oligofructose and its consequences for gut health. Eur J Clin Nutr. 2009 Nov;63(11):1277-89. doi: 10.1038/ejcn.2009.64. Epub 2009 Aug 19.

  PMID: 19690573 BACKGROUND

• 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.

  PMID: 20591206 BACKGROUND

• Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen JP, Delzenne NM. Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut. 2013 Aug;62(8):1112-21. doi: 10.1136/gutjnl-2012-303304. Epub 2012 Nov 7.

  PMID: 23135760 BACKGROUND

• Holscher HD, Bauer LL, Gourineni V, Pelkman CL, Fahey GC Jr, Swanson KS. Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. J Nutr. 2015 Sep;145(9):2025-32. doi: 10.3945/jn.115.217331. Epub 2015 Jul 22.

  PMID: 26203099 BACKGROUND

• Kolida S, Meyer D, Gibson GR. A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans. Eur J Clin Nutr. 2007 Oct;61(10):1189-95. doi: 10.1038/sj.ejcn.1602636. Epub 2007 Jan 31.

  PMID: 17268410 BACKGROUND

• Menne E, Guggenbuhl N, Roberfroid M. Fn-type chicory inulin hydrolysate has a prebiotic effect in humans. J Nutr. 2000 May;130(5):1197-9. doi: 10.1093/jn/130.5.1197.

  PMID: 10801918 BACKGROUND

• 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.

  PMID: 27492975 BACKGROUND

• Petry N, Egli I, Chassard C, Lacroix C, Hurrell R. Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron status. Am J Clin Nutr. 2012 Aug;96(2):325-31. doi: 10.3945/ajcn.112.035717. Epub 2012 Jun 27.

  PMID: 22743314 BACKGROUND

• Huda MN, Lewis Z, Kalanetra KM, Rashid M, Ahmad SM, Raqib R, Qadri F, Underwood MA, Mills DA, Stephensen CB. Stool microbiota and vaccine responses of infants. Pediatrics. 2014 Aug;134(2):e362-72. doi: 10.1542/peds.2013-3937. Epub 2014 Jul 7.

  PMID: 25002669 BACKGROUND

• Huda MN, Ahmad SM, Alam MJ, Khanam A, Kalanetra KM, Taft DH, Raqib R, Underwood MA, Mills DA, Stephensen CB. Bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age. Pediatrics. 2019 Feb;143(2):e20181489. doi: 10.1542/peds.2018-1489.

  PMID: 30674610 BACKGROUND

• Zuckerman JN, Hatz C, Kantele A. Review of current typhoid fever vaccines, cross-protection against paratyphoid fever, and the European guidelines. Expert Rev Vaccines. 2017 Oct;16(10):1029-1043. doi: 10.1080/14760584.2017.1374861.

  PMID: 28856924 BACKGROUND

• Fiorentino M, Lammers KM, Levine MM, Sztein MB, Fasano A. In vitro Intestinal Mucosal Epithelial Responses to Wild-Type Salmonella Typhi and Attenuated Typhoid Vaccines. Front Immunol. 2013 Feb 12;4:17. doi: 10.3389/fimmu.2013.00017. eCollection 2013.

  PMID: 23408152 BACKGROUND

• Salerno-Goncalves R, Galen JE, Levine MM, Fasano A, Sztein MB. Manipulation of Salmonella Typhi Gene Expression Impacts Innate Cell Responses in the Human Intestinal Mucosa. Front Immunol. 2018 Nov 1;9:2543. doi: 10.3389/fimmu.2018.02543. eCollection 2018.

  PMID: 30443257 BACKGROUND

MeSH Terms

Conditions

Inflammation; Typhoid Fever

Interventions

Inulin; maltodextrin; Ty21a typhoid vaccine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides

Study Officials

• Danielle Lemay, PhD

  USDA, ARS, Western Human Nutrition Research Center

  PRINCIPAL INVESTIGATOR

• Ryan Snodgrass, PhD

  USDA, ARS, Western Human Nutrition Research Center

  PRINCIPAL INVESTIGATOR

• Mary Kable, PhD

  USDA, ARS, Western Human Nutrition Research Center

  PRINCIPAL INVESTIGATOR

• Bess Caswell, PhD

  USDA, ARS, Western Human Nutrition Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: September 10, 2020
• Study Start: September 27, 2022
• Primary Completion: June 11, 2025
• Study Completion: June 11, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)