The Effects of Oral Fructanase Administration on Gastrointestinal Symptoms After Inulin Challenge in Healthy Adults

NCT06628869 | Completed DMC

• 2 other identifiers: BCCT-AMS-0011BIO-2407
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The carbohydrate inulin (from chicory root) is a healthy prebiotic ingredient found in dietary supplements and fortified foods (Nagy et al). Inulin is representative of a broader class of typically health-associated, yet fermentable carbohydrates called fructans that occur naturally in many vegetables, fruits, and wheat. Fructans, or long chains of fructose units, are resistant to human digestive enzyme hydrolysis and transit intact to the small intestine and colon where they undergo rapid fermentation by intestinal microbes. This microbial metabolism of fructans produces gas and other fermentation byproducts that can lead to excess gastrointestinal (GI) symptoms like abdominal bloating, cramping, stomach rumbling, and flatulence (Bonnema et al; Briet et al; Bruhwyler et al), especially in individuals with irritable bowel syndrome (Van den Houte et al). A new digestive enzyme called fructanase was developed to help with GI symptoms associated with fructan consumption. Positive findings from in vitro digestion simulations (Guice et al) and a first-in-human safety trial (Garvey et al) helped define the fructanase dose for this clinical trial-the primary objective of which is to investigate the effect of oral fructanase administration on GI symptoms in healthy adults after consuming oatmeal with added inulin (25 grams). Secondary outcomes include breath hydrogen and methane levels, which serve as biomarkers of intestinal microbial fermentation. The investigators hypothesize that fructanase administration will lower the severity of GI symptoms after inulin consumption, as well as lower breath biomarkers of intestinal microbial fermentation, compared to placebo.

Conditions

Digestive Health; Gastrointestinal Health; FODMAP Intolerance; Food Sensitivity

Keywords

digestive enzyme; FODMAP; fructanase; inulinase; fructan hydrolyase; enzyme; food sensitivity; inulin; bloating; flatulence; fermentation; methane; hydrogen; dietary supplement; dietary fiber; food intolerance; fructan; oligosaccharide; fructooligosaccharide; inulinooligosaccharide; fructo-oligosaccharide; inulino-oligosaccharide; non-starch polysaccharidase; NSPase; carbohydrate-active enzyme; CAZyme; microbiome; metagenome; food challenge

Outcome Measures

Primary Outcomes (1)

• Maximum postprandial baseline-adjusted overall abdominal symptoms severity over the 8-hour in-clinic period

  The primary endpoint is the difference in the maximum postprandial baseline-adjusted overall abdominal symptoms visual analog scale (VAS) score over the 8-hour in-clinic period between placebo and fructanase treatments. Participants will rate overall abdominal symptoms severity from "excellent, none at all" (score: 0) to "really awful, the worst it has been" (score: 100). Participants will be instructed to rate themselves by marking the VAS at the point that was most appropriate to their feeling over the prior hour. The distance from the point marked on the VAS to the left end of the scale will be measured in millimeters. The change from baseline is calculated by subtracting the baseline score from the score at each postprandial time point. At Visits 2 and 3 (Days 0 and 7), the VAS will be administered in-clinic at t = -0.25, 1, 2, 3, 4, 5, 6, 7, and 8 hours.

  8 hours

Secondary Outcomes (19)

• Maximum postprandial unadjusted overall abdominal symptoms severity over the 8-hour in-clinic period

  8 hours

• Maximum postprandial baseline-adjusted and unadjusted individual gastrointestinal symptom severity over the 8-hour in-clinic period

  8 hours

• Total gastrointestinal symptom burden over the 8-hour in-clinic period represented by the visual analog scale (VAS) score area-under-the-curve (AUC) and baseline-adjusted positive area-under-the-curve (p-AUC):

  8 hours

• Time to maximum gastrointestinal symptom visual analog scale (VAS) score over the 8-hour in-clinic period

  8 hours

• Maximum 24-hour gastrointestinal symptom visual analog scale (VAS) score, representing the time since leaving the clinic

  24 hours

Study Arms (2)

Fructanase

ACTIVE COMPARATOR

Total 400 inulinase activity units (INU) per dose

Dietary Supplement: Fructanase

Placebo

PLACEBO COMPARATOR

Maltodextrin

Dietary Supplement: Maltodextrin placebo

Interventions

Fructanase DIETARY_SUPPLEMENT

Participants will consume one capsule containing 400 INU inulinase (325 mg, includes maltodextrin) with a mixture of oatmeal (40 grams) and inulin (25 grams). Participants will be directed to consume the capsule after two spoonfuls of oatmeal. The fructanase was obtained from Aspergillus tubingensis.

Also known as: inulinase, fructan hydrolase, beta-fructofuranosidase, beta-fructosidase

Fructanase

Maltodextrin placebo DIETARY_SUPPLEMENT

Participants will consume one capsule containing 300 mg maltodextrin with a mixture of oatmeal (40 grams) and inulin (25 grams). Participants will be directed to consume the capsule after two spoonfuls of oatmeal. The maltodextrin was obtained from tapioca.

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, age ≥20 to ≤50 y at Visit 1 (Day -7).
• BMI ≥18.5 to less than 30.0 kg/m2 at Visit 1 (Day -7).
• Non-user (never used, or former user defined as cessation ≥12 months) of tobacco or nicotine products (e.g., cigarette smoking, vaping, chewing tobacco) with no plans to begin use during the study period.
• Willing to maintain habitual diet, physical activity, and body weight throughout the trial.
• No health conditions that would prevent him/her from fulfilling the study requirements as judged by the Clinical Investigator on the basis of medical history and routine laboratory test results.
• Understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Clinical Investigator.

You may not qualify if:

• Known sensitivity, intolerability, or allergy to any of the study products or their excipients.
• Clinically important GI condition that would potentially interfere with the evaluation of the study product (e.g., inflammatory bowel disease, irritable bowel syndrome, gastroesophageal reflux disease requiring any medication, dyspepsia, Crohn's disease, celiac disease, history of surgery for weight loss, gastroparesis, and clinically significant lactose or gluten intolerance or other food or ingredient allergies).
• Recent (within 2 weeks of Visit 1; Day -7) history of an episode of acute GI illness such as nausea/vomiting or diarrhea (defined as ≥3 loose or liquid stools/d).
• Self-reported history (within 6 weeks of Visit 1; Day -7) of constipation (defined as fewer than 3 bowel movements per week).
• Uncontrolled and/or clinically important pulmonary (including uncontrolled asthma), cardiac (including, but not limited to, atherosclerotic disease, history of myocardial infarction, peripheral arterial disease, stroke), hepatic, renal, endocrine (including Type 1 and Type 2 diabetes mellitus), hematologic, immunologic, neurologic (such as Alzheimer's or Parkinson's disease), psychiatric (including depression and/or anxiety disorders) or biliary disorders. Conditions which are well-controlled or resolved will be assessed by the Clinical Investigator on a case-by-case basis.
• Uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) as defined by the blood pressure measured at Visit 1 (Day -7). Stable use of hypertension medication is allowed \[defined as no change in medication regimen within the 3 months prior to Visit 1 (Day -7)\].
• Have received a COVID-19 vaccine within 2 weeks of randomization or expected to receive a COVID-19 vaccine during the study period.
• Had a positive SARS-CoV2 test and experienced symptoms for more than 2 months (i.e. "long-haulers").
• Extreme dietary habits (e.g., vegetarian, vegan, Atkins diet, etc.) at the discretion of the Clinical Investigator.
• History or presence of cancer in the prior 2 years, except for non-melanoma skin cancer.
• Major trauma or any other surgical event within 3 months of Visit 1 (Day -7).
• Signs or symptoms of an active infection of clinical relevance within 5 days of Visit 1 (Day -7). The visit may be rescheduled such that all signs and symptoms have resolved (at the discretion of the Clinical Investigator) at least 5 days prior to Visit 1 (Day -7).
• Weight loss or gain more than 4.5 kg in the 3 months prior to Visit 1 (Day -7).
• Currently or planning to be on a weight loss regimen during the study.
• Use of weight loss medications, incretin mimetics, and/or GLP-1 agonists in the 3 months prior to Visit 1 (Day -7).

Sponsors & Collaborators

• BIO-CAT, Inc.: lead
• Biofortis, Inc.: collaborator

Study Sites (1)

Biofortis, Inc.

Addison, Illinois, 60101, United States

Location

Related Publications (8)

• Snyder E, Cai B, DeMuro C, Morrison MF, Ball W. A New Single-Item Sleep Quality Scale: Results of Psychometric Evaluation in Patients With Chronic Primary Insomnia and Depression. J Clin Sleep Med. 2018 Nov 15;14(11):1849-1857. doi: 10.5664/jcsm.7478.

  PMID: 30373688 BACKGROUND

• Garvey SM, LeMoire A, Wang J, Lin L, Sharif B, Bier A, Boyd RC, Baisley J. Safety and Tolerability of Microbial Inulinase Supplementation in Healthy Adults: A Randomized, Placebo-Controlled Trial. Gastro Hep Adv. 2024 Jun 21;3(7):920-930. doi: 10.1016/j.gastha.2024.05.013. eCollection 2024.

  PMID: 39318719 BACKGROUND

• Briet F, Achour L, Flourie B, Beaugerie L, Pellier P, Franchisseur C, Bornet F, Rambaud JC. Symptomatic response to varying levels of fructo-oligosaccharides consumed occasionally or regularly. Eur J Clin Nutr. 1995 Jul;49(7):501-7.

  PMID: 7588500 BACKGROUND

• Bruhwyler J, Carreer F, Demanet E, Jacobs H. Digestive tolerance of inulin-type fructans: a double-blind, placebo-controlled, cross-over, dose-ranging, randomized study in healthy volunteers. Int J Food Sci Nutr. 2009 Mar;60(2):165-75. doi: 10.1080/09637480701625697.

  PMID: 18608562 BACKGROUND

• Bonnema AL, Kolberg LW, Thomas W, Slavin JL. Gastrointestinal tolerance of chicory inulin products. J Am Diet Assoc. 2010 Jun;110(6):865-8. doi: 10.1016/j.jada.2010.03.025.

  PMID: 20497775 BACKGROUND

• Guice JL, Hollins MD, Farmar JG, Tinker KM, Garvey SM. Microbial inulinase promotes fructan hydrolysis under simulated gastric conditions. Front Nutr. 2023 May 23;10:1129329. doi: 10.3389/fnut.2023.1129329. eCollection 2023.

  PMID: 37305092 BACKGROUND

• Van den Houte K, Colomier E, Routhiaux K, Marien Z, Schol J, Van den Bergh J, Vanderstappen J, Pauwels N, Joos A, Arts J, Caenepeel P, De Clerck F, Matthys C, Meulemans A, Jones M, Vanuytsel T, Carbone F, Tack J. Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome. Gastroenterology. 2024 Jul;167(2):333-342. doi: 10.1053/j.gastro.2024.02.008. Epub 2024 Feb 23.

  PMID: 38401741 BACKGROUND

• Nagy DU, Sandor-Bajusz KA, Body B, Decsi T, Van Harsselaar J, Theis S, Lohner S. Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses. Crit Rev Food Sci Nutr. 2023 Nov;63(33):12018-12035. doi: 10.1080/10408398.2022.2098246. Epub 2022 Jul 14.

  PMID: 35833477 BACKGROUND

MeSH Terms

Conditions

Food Intolerance; Flatulence

Interventions

levanase; inulinase; beta-Fructofuranosidase

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Aditi M. Shaw, MD

  Biofortis, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2024
• First Posted: October 8, 2024
• Study Start: November 4, 2024
• Primary Completion: December 16, 2024
• Study Completion: December 17, 2024
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)