Study Summary
This trial will test whether adding dietary fiber, in the form of inulin, to a diet lacking in fiber will raise levels of potentially beneficial gut bacteria, such as Bifidobacterium. The investigators will examine how inulin affects gut health and immune response, including to vaccines.
Eligible Conditions
- Inflammation
- Typhoid
- Vaccines
- Leaky Gut Syndrome
Treatment Effectiveness
Study Objectives
6 Primary · 41 Secondary · Reporting Duration: 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
Day 26 and 58
Change in plasma antibody response to typhoid vaccination
Change in vaccine-specific serum antibody response to typhoid vaccination
Day 26
Typhoid Fever
Change in whole blood antibody response to typhoid vaccination
Day 26
Change in fecal antibody levels from typhoid vaccination
Change in vaccine-specific fecal IgA antibody levels from typhoid vaccination
Day 36
Change in T-cell response to typhoid vaccination
Day 36
Change in antibody response to typhoid vaccination
Day 7
Change in fecal myeloperoxidase
Change in fecal neopterin
Day 8
Body Weight Changes
Change in blood monocyte subsets
Change in plasma acute phase proteins
Change in plasma acute phase proteins and adhesion molecules
Change in plasma adhesion molecules
Change in plasma chemokines
Change in plasma cytokines as markers of systemic inflammation
Change in plasma myeloperoxidase
Change in plasma neopterin
Body Weight Changes
Day 8
Change in urinary D-mannitol
Change in urinary lactulose
Change in urinary lactulose and D-mannitol
Day 8
Change in markers of inflammation
Day 8
Change in marker of lipopolysaccharide (LPS) exposure
Change in plasma D-lactate
Change in plasma citrulline
Change in plasma diamine oxidase
Change in plasma intestinal fatty acid binding protein
Change in urinary sucralose
Day 58
Change in GI symptoms
Change in fecal SCFA
Change in fecal bile acids
Change in fecal calprotectin
Change in fecal calprotectin secretory immunoglobulin A (sIgA)
Change in fecal mRNA
Change in fecal metabolites
Change in fecal microbiome
Change in fecal microbiome function
Change in fecal microbiome identity
Change in fecal pH
Change in fecal secretory immunoglobulin A (sIgA)
Change in fecal secretory total immunoglobulin A (sIgA)
Change in stool consistency
Change in stool consistency and frequency
Day 58
Changes in dietary intake
Pre-study
Baseline dietary fiber intake
Trial Safety
Trial Design
2 Treatment Groups
Inulin and Ty21a Vaccine
1 of 2
Maltodextrin and Ty21a Vaccine
1 of 2
Experimental Treatment
Non-Treatment Group
60 Total Participants · 2 Treatment Groups
Primary Treatment: Inulin · Has Placebo Group · Phase < 1
Inulin and Ty21a VaccineExperimental Group · 2 Interventions: Inulin, Ty21a Typhoid Fever Vaccine · Intervention Types: DietarySupplement, Biological
Maltodextrin and Ty21a VaccinePlaceboComparator Group · 2 Interventions: Maltodextrin, Ty21a Typhoid Fever Vaccine · Intervention Types: DietarySupplement, Biological
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Inulin
2011
Completed Phase 4
~780
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: 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
Who is running the clinical trial?
USDA, Western Human Nutrition Research CenterLead Sponsor
59 Previous Clinical Trials
20,958 Total Patients Enrolled
6 Trials studying Inflammation
552 Patients Enrolled for Inflammation
University of MinnesotaOTHER
1,272 Previous Clinical Trials
1,487,990 Total Patients Enrolled
16 Trials studying Inflammation
1,339 Patients Enrolled for Inflammation
Danielle Lemay, PhDPrincipal InvestigatorUSDA, ARS, Western Human Nutrition Research Center
2 Previous Clinical Trials
405 Total Patients Enrolled
1 Trials studying Inflammation
10 Patients Enrolled for Inflammation
Charles Stephensen, PhDPrincipal InvestigatorUSDA, ARS, Western Human Nutrition Research Center
1 Previous Clinical Trials
23 Total Patients Enrolled
Mary Kable, PhDPrincipal InvestigatorUSDA, ARS, Western Human Nutrition Research Center
Eligibility Criteria
Age 18 - 50 · All Participants · 5 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:Your body mass index (BMI) falls between 18.5 and 30.9 kg/m2.
Men between the ages of 18-30 who drink less than 34 grams of alcohol per day.
Women between 18 and 30 years old who drink less than 28 grams of alcohol per day.
Women between the ages of 31 and 50 years old who consume less than 25 grams of alcohol per day are eligible.
Men between 31-50 years of age who consume less than 31 grams of alcohol per day.
References
- Meyer, D, and M Stasse-Wolthuis. 2009. “The Bifidogenic Effect of Inulin and Oligofructose and Its Consequences for Gut Health”. European Journal of Clinical Nutrition. Springer Science and Business Media LLC. doi:10.1038/ejcn.2009.64.
- Kolida, S, D Meyer, and G R Gibson. 2007. “A Double-blind Placebo-controlled Study to Establish the Bifidogenic Dose of Inulin in Healthy Humans”. European Journal of Clinical Nutrition. Springer Science and Business Media LLC. doi:10.1038/sj.ejcn.1602636.
- Menne, Evelyne, Nicolas Guggenbuhl, and Marcel Roberfroid. 2000. “Fn-type Chicory Inulin Hydrolysate Has a Prebiotic Effect in Humans”. The Journal of Nutrition. Oxford University Press (OUP). doi:10.1093/jn/130.5.1197.
- Micka, Antje, Anne Siepelmeyer, Anja Holz, Stephan Theis, and Christiane Schön. 2016. “Effect of Consumption of Chicory Inulin on Bowel Function in Healthy Subjects with Constipation: A Randomized, Double-blind, Placebo-controlled Trial”. International Journal of Food Sciences and Nutrition. Informa UK Limited. doi:10.1080/09637486.2016.1212819.
- Huda, M. Nazmul, Zachery Lewis, Karen M. Kalanetra, Mamunur Rashid, Shaikh M. Ahmad, Rubhana Raqib, Firdausi Qadri, Mark A. Underwood, David A. Mills, and Charles B. Stephensen. 2014. “Stool Microbiota and Vaccine Responses of Infants”. Pediatrics. American Academy of Pediatrics (AAP). doi:10.1542/peds.2013-3937.
- Zuckerman, Jane N, Christoph Hatz, and Anu Kantele. 2017. “Review of Current Typhoid Fever Vaccines, Cross-protection Against Paratyphoid Fever, and the European Guidelines”. Expert Review of Vaccines. Informa UK Limited. doi:10.1080/14760584.2017.1374861.
- Costabile, Adele, Sofia Kolida, Annett Klinder, Eva Gietl, Michael Bäuerlein, Claus Frohberg, Volker Landschütze, and Glenn R. Gibson. 2010. “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”. British Journal of Nutrition. Cambridge University Press (CUP). doi:10.1017/s0007114510001571.
- Petry, Nicolai, Ines Egli, Christophe Chassard, Christophe Lacroix, and Richard Hurrell. 2012. “Inulin Modifies the Bifidobacteria Population, Fecal Lactate Concentration, and Fecal Ph but Does Not Influence Iron Absorption in Women with Low Iron Status”. The American Journal of Clinical Nutrition. Oxford University Press (OUP). doi:10.3945/ajcn.112.035717.
- Holscher, Hannah D, Laura L Bauer, Vishnupriya Gourineni, Christine L Pelkman, George C Fahey Jr., and Kelly S Swanson. 2015. “Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-blind, Placebo-controlled, Crossover Trial”. The Journal of Nutrition. Oxford University Press (OUP). doi:10.3945/jn.115.217331.
- Huda, M. Nazmul, Shaikh M. Ahmad, M. Jahangir Alam, Afsana Khanam, Karen M. Kalanetra, Diana H. Taft, Rubhana Raqib, Mark A. Underwood, David A. Mills, and Charles B. Stephensen. 2019. “bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age”. Pediatrics. American Academy of Pediatrics (AAP). doi:10.1542/peds.2018-1489.
- Salerno-Gonçalves, Rosângela, James E. Galen, Myron M. Levine, Alessio Fasano, and Marcelo B. Sztein. 2018. “Manipulation of Salmonella Typhi Gene Expression Impacts Innate Cell Responses in the Human Intestinal Mucosa”. Frontiers in Immunology. Frontiers Media SA. doi:10.3389/fimmu.2018.02543.
- Dewulf, Evelyne M, Patrice D Cani, Sandrine P Claus, Susana Fuentes, Philippe GB Puylaert, Audrey M Neyrinck, Laure B Bindels, et al.. 2012. “Insight into the Prebiotic Concept: Lessons from an Exploratory, Double Blind Intervention Study with Inulin-type Fructans in Obese Women”. Gut. BMJ. doi:10.1136/gutjnl-2012-303304.
- Fiorentino, Maria, Karen M. Lammers, Myron M. Levine, Marcelo B. Sztein, and Alessio Fasano. 2013. “In Vitro Intestinal Mucosal Epithelial Responses to Wild-type Salmonella Typhi and Attenuated Typhoid Vaccines”. Frontiers in Immunology. Frontiers Media SA. doi:10.3389/fimmu.2013.00017.
- Huda, M. Nazmul, Shaikh M. Ahmad, M. Jahangir Alam, Afsana Khanam, Karen M. Kalanetra, Diana H. Taft, Rubhana Raqib, Mark A. Underwood, David A. Mills, and Charles B. Stephensen. 2019. “bifidobacterium Abundance in Early Infancy and Vaccine Response at 2 Years of Age”. Pediatrics. American Academy of Pediatrics (AAP). doi:10.1542/peds.2018-1489.
- Holscher, Hannah D, Laura L Bauer, Vishnupriya Gourineni, Christine L Pelkman, George C Fahey Jr., and Kelly S Swanson. 2015. “Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults Participating in a Randomized, Double-blind, Placebo-controlled, Crossover Trial”. The Journal of Nutrition. Oxford University Press (OUP). doi:10.3945/jn.115.217331.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 2022. "WHNRC (Western Human Nutrition Research Center) Fiber Intervention Study". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04543877.
Frequently Asked Questions
Is octogenarian age a permissible criterion for enrollment in this research study?
"In accordance with the requirements for enrollment, individuals must be between 18 and 50 years of age to qualify." - Anonymous Online Contributor
Unverified Answer
Are there any eligibility requirements for participation in this research trial?
"This research effort is seeking 60 individuals aged 18-50 with inflammation to participate. To be considered, applicants must satisfy the following parameters: Body Mass Index (BMI) of 18.5 - 30.9 kg/m2; females between ages 18 and 30 should consume no greater than 28 g/day while males in this age bracket cannot exceed 34 g/day; finally, for male and female participants over 31 years old, a maximum daily intake of 25g and 31g respectively is prescribed." - Anonymous Online Contributor
Unverified Answer
Are there any antecedent studies regarding the use of Inulin?
"Currently, there are 4 ongoing trials of Inulin in development, with none reaching Phase 3. Most trails for this medicine are located near Baltimore, Maryland but other centres across the USA have studies underway as well." - Anonymous Online Contributor
Unverified Answer
How many participants have been accepted into this research project?
"Affirmative. Clinicaltrial.gov data points to the fact that this trial is currently seeking participants, with an initial posting on September 27th 2022 and a final update being made November 29th of the same year. 60 people need to be enrolled at one location for successful completion." - Anonymous Online Contributor
Unverified Answer
Are there any available patient slots for this clinical research project?
"Data on clinicaltrials.gov indicates that this trial is presently recruiting potential participants, which first appeared on September 27th 2022 and was last revised November 29th 2022." - Anonymous Online Contributor
Unverified Answer
What results are researchers expecting from this clinical research?
"This clinical trial seeks to identify a change in antibody response to typhoid vaccination within Days 26, 37 and 39. Secondary objectives include assessing dietary fibre intake with a food frequency questionnaire, measuring acute phase reactants C-reactive protein (CRP) and serum amyloid A (SAA), as well as determining the relative abundance of colonic bacteria via polymerase chain reaction amplification and sequencing of 16s ribosomal RNA from stool samples collected 3 times per period." - Anonymous Online Contributor
Unverified Answer