Safety and Tolerability Trial of Microbial Inulinase

NCT05744700 | Completed

• 2 other identifiers: B03-22-01-T0037BCCT-AB-0009
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of this clinical trial are to: 1) assess the effect of microbial inulinase on gastrointestinal symptoms in healthy participants compared to a placebo, and 2) to assess the safety and tolerability of microbial inulinase in healthy participants compared to a placebo.

Conditions

Digestive Health; Gastrointestinal Health

Outcome Measures

Primary Outcomes (47)

• Gastrointestinal Symptom Rating Scale score

  Between placebo and inulinase treatments, change from baseline to Day 7, Day 14, Day 21, and Day 28 in Gastrointestinal Symptom Rating Scale scores (overall score and domain scores). All 15 questions are rated using a 7-point Likert scale (1 to 7), where lower ratings represent a better outcome or less discomfort.

  4 weeks

• Gastrointestinal Symptom Rating Scale improvement

  Between placebo and inulinase treatments, percentage of participants showing improvement from baseline to Day 28 as assessed by reduction of Gastrointestinal Symptom Rating scores (overall score and domain scores). All 15 questions are rated using a 7-point Likert scale (1 to 7), where lower ratings represent a better outcome or less discomfort.

  4 weeks

• Abdominal discomfort, bloating, and burping scores

  Between placebo and inulinase treatments, change from baseline to Day 7, Day 14, Day 21, and Day 28 on individual Gastrointestinal Symptom Rating Scale questions on abdominal discomfort, bloating, and burping. These 3 questions are rated using a 7-point Likert scale (1 to 7), where lower ratings represent a better outcome or less discomfort.

  4 weeks

• Plasma lactate

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting plasma lactate concentration (mmol/L)

  4 weeks

• Serum insulin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum insulin concentration (pmol/L)

  4 weeks

• Serum uric acid

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum uric acid concentration (umol/L)

  4 weeks

• Serum high-sensitivity C-reactive protein (hsCRP)

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum hsCRP concentration (mg/L)

  4 weeks

• Serum total cholesterol

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total cholesterol concentration (mmol/L)

  4 weeks

• Serum low-density lipoprotein (LDL) cholesterol

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum LDL cholesterol concentration (mmol/L)

  4 weeks

• Serum high-density lipoprotein (HDL) cholesterol

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum HDL cholesterol concentration (mmol/L)

  4 weeks

• Plasma high-density lipoprotein (HDL) cholesterol

  Between placebo and inulinase treatments, change from screening to Day 28 in fasting plasma HDL cholesterol concentration (mg/dL)

  6 weeks

• Serum triglycerides

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum triglycerides concentration (mmol/L)

  4 weeks

• Serum albumin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum albumin concentration (g/L)

  4 weeks

• Serum alkaline phosphatase

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alkaline phosphatase concentration (U/L)

  4 weeks

• Serum alanine transaminase

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alanine transaminase concentration (U/L)

  4 weeks

• Serum aspartate transaminase

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum aspartate transaminase concentration (U/L)

  4 weeks

• Serum chloride

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum chloride concentration (mmol/L)

  4 weeks

• Serum creatinine

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum creatinine concentration (umol/L)

  4 weeks

• Serum globulin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum globulin concentration (g/L)

  4 weeks

• Serum glucose

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum glucose concentration (mmol/L)

  4 weeks

• Serum potassium

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum potassium concentration (mmol/L)

  4 weeks

• Serum sodium

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum sodium concentration (mmol/L)

  4 weeks

• Serum total bilirubin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total bilirubin concentration (umol/L)

  4 weeks

• Serum total protein

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total protein concentration (g/L)

  4 weeks

• Whole blood basophils

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood basophil count (x 10\^9/L)

  4 weeks

• Whole blood eosinophils

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood eosinophil count (x 10\^9/L)

  4 weeks

• Whole blood hematocrit

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hematocrit (as volume percent)

  4 weeks

• Whole blood hemoglobin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hemoglobin concentration (g/dL)

  4 weeks

• Whole blood lymphocytes

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood lymphocyte count (x 10\^9/L)

  4 weeks

• Whole blood mean corpuscular hemoglobin

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular hemoglobin (pg)

  4 weeks

• Whole blood mean corpuscular hemoglobin concentration

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular hemoglobin concentration (g/L)

  4 weeks

• Whole blood mean corpuscular volume

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular volume (fL)

  4 weeks

• Whole blood monocytes

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood monocyte count (x 10\^9/L)

  4 weeks

• Whole blood neutrophils

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood neutrophil count (x 10\^9/L)

  4 weeks

• Whole blood platelets

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood platelet count (x 10\^9/L)

  4 weeks

• Whole blood mean platelet volume

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean platelet volume (fL)

  4 weeks

• Whole blood red blood cells

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood red blood cell count (x 10\^9/L)

  4 weeks

• Whole blood red blood cell distribution width

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood red blood cell distribution width

  4 weeks

• Whole blood white blood cells

  Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood white blood cell count (x 10\^9/L)

  4 weeks

• Whole blood hemoglobin A1c (HbA1c)

  Fasting whole blood HbA1c concentration at Day 1 (%)

  Day 1

• Estimated glomerular filtration (eGFR)

  Between placebo and inulinase treatments, change from baseline to Day 28 in eGFR (mL/min/1.73m\^2)

  4 weeks

• Blood pressure

  Resting systolic blood pressure over resting diastolic blood pressure (mmHg/mmHg)

  4 weeks

• Heart rate

  Resting heart rate (beats per minute)

  4 weeks

• Body weight

  Body weight (kg)

  4 weeks

• Body mass index

  Body mass index (kg/m\^2)

  4 weeks

• Incidence of adverse events

  Number of participants with adverse events

  4 weeks

• Incidence of serious adverse events

  Number of participants with serious adverse events

  4 weeks

Study Arms (2)

Inulinase

ACTIVE COMPARATOR

Total 2,000 INU inulinase per day for 28 days

Dietary Supplement: Inulinase

Placebo

PLACEBO COMPARATOR

Maltodextrin for 28 days

Dietary Supplement: Maltodextrin placebo

Interventions

Inulinase DIETARY_SUPPLEMENT

Participants will consume one capsule containing 1,000 INU inulinase, twice daily, for 28 days. Participants will be directed to consume the capsules with their two largest meals.

Also known as: Fructan hydrolyase, Beta-fructofuranosidase

Inulinase

Maltodextrin placebo DIETARY_SUPPLEMENT

Participants will consume one capsule containing maltodextrin, twice daily, for 28 days. Participants will be directed to consume the capsules with their two largest meals.

Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult participants who are 20 to 60 years of age at screening (inclusive)
• In good general health (no uncontrolled diseases or conditions) as deemed by the investigator and able to consume the study product
• Regularly consumes at least 2 meals per day
• Has a body mass index (BMI) between 18.5 to 29.9 kg/m\^2 (inclusive) at Visit 2
• Completes the run-in period with ≥ 90% product compliance for both consumption of doses and timing of doses as assessed by daily diary
• Completes the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire during the run-in period
• Individuals with childbearing potential must agree to practice an acceptable form of birth control for a certain time frame prior to the first dose of study product and throughout the study
• Has maintained stable use of medication and supplements, and stable dietary and lifestyle habits, for the last 3 months prior to screening and agree to maintain them throughout the study
• Agree to avoid strenuous exercise 24 hours prior to each visit
• Willing to limit daily alcohol consumption to no more than 3-4 drinks per day throughout the study
• Willing to maintain current use of cannabinoids (if applicable) throughout the study
• Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures

You may not qualify if:

• Individuals who are lactating, pregnant, or planning to become pregnant during the study
• Has a known sensitivity, intolerability, or allergy to any of the study products or their excipients
• Received a vaccine for COVID-19 (coronavirus disease 2019) in the 2 weeks prior to screening or plans to receive a vaccine for COVID-19 during the study period, currently has COVID-19 or tests positive for COVID-19 within 28 days prior to baseline visit, or currently has any post COVID-19 condition(s) as defined by World Health Organization
• Recent (within 2 weeks of Visit 1) history of an episode of acute gastrointestinal illness such as nausea, vomiting, or diarrhea
• Have a history of irritable bowel syndrome, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), functional constipation or diarrhea (defined by the Rome IV diagnostic criteria), celiac disease, malabsorption, gastroparesis, diverticulosis, gastric or duodenal ulcers, pancreatitis, or eating disorder; or have a history of intestinal surgery (excluding appendectomy or herniorrhaphy) or bariatric surgery.
• Have an abnormality or obstruction of the gastrointestinal tract precluding swallowing (e.g., dysphagia) and/or digestion (e.g., history of bowel obstruction)
• Participated in upper gastrointestinal endoscopy and/or colonoscopy or preparation within 3 months prior to Visit 1
• Diagnosed with hypercholesterolemia or hypertriglyceridemia \[i.e., elevated fasting low-density lipoprotein (LDL) (≥ 135 mg/dL; ≥ 3.5 mmol/L) or elevated triglycerides (≥ 150 mg/dL; ≥ 1.7 mmol/L) at screening\]
• Has a history of heart disease/cardiovascular disease, uncontrolled hypertension (≥ 140 systolic or ≥ 90 diastolic mmHg), kidney disease (dialysis or renal failure), hepatic impairment or disease
• Is Type I or Type II diabetic or pre-diabetic \[i.e., elevated fasting blood glucose levels (≥ 100 mg/dL; ≥ 5.6 mmol/L) and/or elevated hemoglobin A1c (≥ 6.0%) at screening\]
• Has a history of liver or gallbladder disease or stomach ulcers
• Has a positive medical history of unstable thyroid disease, previously diagnosed major affective disorder, psychiatric disorder that required hospitalization in the prior year, immune disorders and/or immunocompromised
• Diagnosed with cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to the screening visit, or any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential participant at risk because of participation in the study, or influences the results or the potential participant's ability to participate in the study
• Major surgery in 3 months prior to screening or planned major surgery during the study
• History of alcohol or substance abuse (including cannabinoids) in the 12 months prior to screening (including having been hospitalized for such in an in-patient or out-patient intervention program)

Sponsors & Collaborators

• BIO-CAT, Inc.: lead
• Nutrasource Pharmaceutical and Nutraceutical Services, Inc.: collaborator

Study Sites (1)

Nutrasource site (Apex Trials)

Guelph, Ontario, N1G 0B4, Canada

Location

Related Publications (6)

• 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

• Dionne J, Ford AC, Yuan Y, Chey WD, Lacy BE, Saito YA, Quigley EMM, Moayyedi P. A Systematic Review and Meta-Analysis Evaluating the Efficacy of a Gluten-Free Diet and a Low FODMAPs Diet in Treating Symptoms of Irritable Bowel Syndrome. Am J Gastroenterol. 2018 Sep;113(9):1290-1300. doi: 10.1038/s41395-018-0195-4. Epub 2018 Jul 26.

  PMID: 30046155 BACKGROUND

• Lin MY, Dipalma JA, Martini MC, Gross CJ, Harlander SK, Savaiano DA. Comparative effects of exogenous lactase (beta-galactosidase) preparations on in vivo lactose digestion. Dig Dis Sci. 1993 Nov;38(11):2022-7. doi: 10.1007/BF01297079.

  PMID: 8223076 BACKGROUND

• Di Stefano M, Miceli E, Gotti S, Missanelli A, Mazzocchi S, Corazza GR. The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms. Dig Dis Sci. 2007 Jan;52(1):78-83. doi: 10.1007/s10620-006-9296-9. Epub 2006 Dec 7.

  PMID: 17151807 BACKGROUND

• Ido H, Matsubara H, Kuroda M, Takahashi A, Kojima Y, Koikeda S, Sasaki M. Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study. Clin Transl Gastroenterol. 2018 Sep 19;9(9):181. doi: 10.1038/s41424-018-0052-1.

  PMID: 30228265 BACKGROUND

• Machnicki G, Pefaur J, Gaite L, Linchenco AM, Raimondi C, Schiavelli R, Otero A, Margolis MK. Gastrointestinal (GI)-Specific patient reported outcomes instruments differentiate between renal transplant patients with or without GI symptoms: results from a South American cohort. Health Qual Life Outcomes. 2008 Jul 21;6:53. doi: 10.1186/1477-7525-6-53.

  PMID: 18644133 BACKGROUND

MeSH Terms

Interventions

inulinase; beta-Fructofuranosidase

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Anthony Bier, MD, CCFP

  Apex Trials

  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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: February 27, 2023
• Study Start: April 28, 2023
• Primary Completion: October 6, 2023
• Study Completion: October 6, 2023
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)