WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study

NCT ID: NCT04543877

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-27

Study Completion Date

2025-06-11

Brief Summary

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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

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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.

Conditions

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Inflammation Vaccine Intestinal Permeability Typhoid Fever

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Inulin

Intervention Type DIETARY_SUPPLEMENT

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

Ty21a Typhoid Fever Vaccine

Intervention Type 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.

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.

Group Type PLACEBO_COMPARATOR

Maltodextrin

Intervention Type DIETARY_SUPPLEMENT

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

Ty21a Typhoid Fever Vaccine

Intervention Type 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.

Interventions

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Inulin

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

Intervention Type DIETARY_SUPPLEMENT

Maltodextrin

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

Intervention Type DIETARY_SUPPLEMENT

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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Orafti GR Maltrin M100 Vivotif

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Minnesota

OTHER

Sponsor Role collaborator

USDA, Western Human Nutrition Research Center

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Danielle Lemay, PhD

Role: PRINCIPAL_INVESTIGATOR

USDA, ARS, Western Human Nutrition Research Center

Ryan Snodgrass, PhD

Role: PRINCIPAL_INVESTIGATOR

USDA, ARS, Western Human Nutrition Research Center

Mary Kable, PhD

Role: PRINCIPAL_INVESTIGATOR

USDA, ARS, Western Human Nutrition Research Center

Bess Caswell, PhD

Role: PRINCIPAL_INVESTIGATOR

USDA, ARS, Western Human Nutrition Research Center

Locations

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USDA, ARS, Western Human Nutrition Research Center

Davis, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 19690573 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20591206 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23135760 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26203099 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17268410 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10801918 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27492975 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22743314 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25002669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30674610 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28856924 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23408152 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30443257 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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FL113

Identifier Type: -

Identifier Source: org_study_id