Digestive HealthNCT05744700
Safety and Tolerability Trial of Microbial Inulinase
A study testing Inulinase in people with Digestive Health and Gastrointestinal Health, run by BIO-CAT, Inc. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Digestive Health, Gastrointestinal Health
- What is being tested?
- Inulinase
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- 28 Apr 2023to 6 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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)
- Extreme dietary habits at the discretion of the Qualified Investigator, evidenced by a diet wherein the ratio of individual macronutrients and dietary fiber is markedly different than the typical American diet [e.g., ketogenic diet, Atkins diet, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet, vegetarian diet, fruitarian diet, etc.]
- Use of any treatment listed in Study Protocol (No. B03-22-01-T0037) Section 6.5 (Concomitant Treatments) outside of the permitted time frames and/or conditions.
- Receipt or use of investigational products in another research study within 28 days prior to baseline (Visit 2) or longer if the previous investigational product is deemed by the investigator to have lasting effects that might influence the eligibility criteria or outcomes of current study
- Self-report of blood donation totaling between 101 mL to 449 mL of blood within 30 days prior to screening or a blood donation of more than 450 mL within 56 days prior to baseline
- Self-report of donating plasma (e.g., plasmapheresis) within 14 days prior to screening.
- Any other active or unstable medical conditions or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Determine the Safety and Tolerability of Microbial Inulinase
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.
Read the detailed description
Dietary FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) can be digestively bothersome for certain fiber-intolerant individuals, as well as those with irritable bowel syndrome (Dionne et al.). Oral supplementation of microbial enzymes is a promising strategy to ameliorate gastrointestinal (GI) symptoms-such as bloating, abdominal discomfort, and gas-that are associated with food intolerances. Oral enzyme supplementation with fungal beta-galactosidase (lactase), fungal alpha-galactosidase, and a mixture of microbial and plant proteases have previously been clinically shown to effectively reduce GI symptoms associated with dairy, legume, and gluten consumption, respectively (Lin et al.; Di Stefano et al.; Ido et al.). While alpha-galactosidase effectively hydrolyzes galactan-type FODMAPs, there remains a need to target fructan-type FODMAPs. Preclinical data using an in vitro static GI digestion model showed that the microbial enzyme inulinase can effectively digest fructan-rich substrates (e.g., inulin from chicory root, garlic, and a high-fructan meal mash) better than control conditions under simulated gastric conditions (Guice et al., submitted).
The present study is a randomized, double-blind, placebo-controlled clinical trial to determine the safety and tolerability of microbial inulinase as a digestive enzyme supplement in healthy adults. This clinical trial will include 60 participants who are healthy adults between the ages of 20 to 60 and who regularly consume at least two meals daily. The study duration will be up to 62 days. This trial consists of one screening visit (Visit 1, Day -30 to -15), a baseline visit (Visit 2, Day 1), and an end-of-study visit (Visit 3, Day 29 ± 3).
To assess the effect of inulinase on GI-related symptoms, participants will fill out the paper Gastrointestinal Symptom Rating Scale (GSRS) on a weekly basis over the course of the study. The GSRS is a validated questionnaire containing 15 questions used to assess symptoms that are commonly associated with GI disorders (Machnicki et al.). All 15 questions are rated using a 7-point Likert scale, where higher ratings represent more discomfort. The GSRS score is determined by the score of five subscales: reflux, diarrhea, abdominal Pain, indigestion, and constipation. The reflux score will be calculated as an average score of questions 2 and 3. The diarrhea score will be calculated as an average score of questions 11,12, and 14. The abdominal pain score will be calculated as an average score of questions 1, 4, and 5. The indigestion score will be calculated as an average score of questions 6, 7, 8, and 9. The constipation score will be calculated as an average score of questions 10, 13, and 15. Each subscale score is the domain score. The average of all 5 domain scores will give the GSRS score. The GSRS score and 5 sub-scale (domain) scores will be used for analysis. The scores in Visit 2 will be treated as baseline, and change from baseline to Week 1, Week 2, Week 3, and Week 4 will be calculated, as well as the proportion of participants showing improved scores.
At screening Visit 1 (up to 30 days and no less than 15 days prior to the baseline visit), participants will arrive at the clinic in a fasting state (≥ 10 hours). After participants provide voluntary informed consent, the following information will be recorded, and procedures carried out:
- Collect demographic data (age, sex, ethnicity and race)
- Review medical/health history
- Review/record dietary and lifestyle habits
- Review/record use of concomitant treatments
- Review inclusion/exclusion criteria
- Take anthropometric measurements [height (screening only), weight) and vital signs [heart rate (HR) and blood pressure (BP)]
- Calculate body mass index (BMI; kg/m^2)
- Perform a brief symptom-based physical exam, if necessary
- Collect blood for hematology, clinical chemistry, lipid profile, and hemoglobin A1c (HbA1c)
- Dispense GSRS questionnaire for in-clinic completion
- Dispense GSRS questionnaire for at-home use
- Dispense study product (placebo only) and study diary
After confirming eligibility, from Day -14 to Day -1 (the day prior to baseline visit on Day 1), all participants will complete a 2-week run-in period where they will orally consume the placebo capsule twice daily with their usual two largest meals of the day (one capsule per meal) with the same two meals each day.
At baseline Visit 2 (Day 1), participants will arrive at the clinic in a fasting state (≥ 10 hours). The following visit procedures will occur:
- Collect and review any unused study product
- Review the study diary to assess compliance, concomitant treatments, medical conditions, and changes in health
- Review inclusion/exclusion criteria
- Review medical/health history
- Review any changes in dietary and lifestyle habits
- Take anthropometric measurements and vital signs (HR and BP)
- Calculate BMI using height collected from screening
- Collect blood for hematology, clinical chemistry, and lipid profiling
- Collect blood for lactate, insulin, uric acid, and high sensitivity C-reactive protein (hsCRP)
- Collect urine for pregnancy test
- Collect the GSRS questionnaire completed during the run-in period
- Dispense GSRS questionnaire for the participant to complete in-clinic
- Dispense GSRS questionnaire for at-home use
- Randomize the participant to inulinase or placebo
- Dose of study product in-clinic
- Adverse Event (AE) monitoring
- Dispense study products and study diary for home use by the participant
At the baseline visit on Day 1, participants will be randomized in a 1:1 ratio to either study product [1,000 units of inulinase activity (INU) per serving] or placebo and then start the 28 ± 3 days of twice daily study product consumption. Study product will be taken in the same manner (1 capsule taken twice daily with their two usual larger meals of the day).
At end-of-study Visit 3 (Day 29 ± 3), participants will arrive at the clinic in a fasting state (≥ 10 hours). The following visit procedures will occur:
- Return any unused study product and packaging of used study product
- Collect and review the study diary to assess compliance
- Review any changes in dietary and lifestyle habits
- Measure vital signs (BP and HR) and weight, and calculate BMI
- Collect urine for pregnancy test
- Collect blood for hematology, clinical chemistry, and lipid profiling
- Collect blood for lactate, insulin, uric acid, and hsCRP
- Collect the GSRS questionnaire and review for completion
- Dispense GSRS questionnaire for the participant to complete in-clinic
- AE monitoring
- Conditions
- Digestive Health, Gastrointestinal Health
- Being tested
- Inulinase, Maltodextrin placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InulinaseDietary supplement
Also called Fructan hydrolyase, Beta-fructofuranosidase
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.
Maltodextrin placeboDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| Inulinase | Active comparator | Total 2,000 INU inulinase per day for 28 days Receives: Dietary Supplement: Inulinase |
| Placebo | Placebo comparator | Maltodextrin for 28 days Receives: Dietary Supplement: Maltodextrin placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 4 weeks
Plasma lactate
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting plasma lactate concentration (mmol/L)
Measured: 4 weeks
Serum insulin
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum insulin concentration (pmol/L)
Measured: 4 weeks
Serum uric acid
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum uric acid concentration (umol/L)
Measured: 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)
Measured: 4 weeks
Serum total cholesterol
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total cholesterol concentration (mmol/L)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 6 weeks
Serum triglycerides
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum triglycerides concentration (mmol/L)
Measured: 4 weeks
Serum albumin
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum albumin concentration (g/L)
Measured: 4 weeks
Serum alkaline phosphatase
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alkaline phosphatase concentration (U/L)
Measured: 4 weeks
Serum alanine transaminase
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alanine transaminase concentration (U/L)
Measured: 4 weeks
Serum aspartate transaminase
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum aspartate transaminase concentration (U/L)
Measured: 4 weeks
Serum chloride
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum chloride concentration (mmol/L)
Measured: 4 weeks
Serum creatinine
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum creatinine concentration (umol/L)
Measured: 4 weeks
Serum globulin
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum globulin concentration (g/L)
Measured: 4 weeks
Serum glucose
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum glucose concentration (mmol/L)
Measured: 4 weeks
Serum potassium
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum potassium concentration (mmol/L)
Measured: 4 weeks
Serum sodium
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum sodium concentration (mmol/L)
Measured: 4 weeks
Serum total bilirubin
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total bilirubin concentration (umol/L)
Measured: 4 weeks
Serum total protein
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total protein concentration (g/L)
Measured: 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)
Measured: 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)
Measured: 4 weeks
Whole blood hematocrit
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hematocrit (as volume percent)
Measured: 4 weeks
Whole blood hemoglobin
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hemoglobin concentration (g/dL)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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)
Measured: 4 weeks
Whole blood hemoglobin A1c (HbA1c)
Fasting whole blood HbA1c concentration at Day 1 (%)
Measured: Day 1
Estimated glomerular filtration (eGFR)
Between placebo and inulinase treatments, change from baseline to Day 28 in eGFR (mL/min/1.73m^2)
Measured: 4 weeks
Blood pressure
Resting systolic blood pressure over resting diastolic blood pressure (mmHg/mmHg)
Measured: 4 weeks
Heart rate
Resting heart rate (beats per minute)
Measured: 4 weeks
Body weight
Body weight (kg)
Measured: 4 weeks
Body mass index
Body mass index (kg/m^2)
Measured: 4 weeks
Incidence of adverse events
Number of participants with adverse events
Measured: 4 weeks
Incidence of serious adverse events
Number of participants with serious adverse events
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start28 Apr 2023
- Primary completion6 Oct 2023
- Study completion6 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Digestive HealthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- BIO-CAT, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
- Responsible party
- Sponsor
- Investigators
- Anthony Bier, MD, CCFP, Principal investigator, Apex Trials
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05744700
- Sponsor's protocol ID
- B03-22-01-T0037
- Other IDs
- BCCT-AB-0009
- Status last verified
- Sep 2024
- First submitted
- 16 Feb 2023
- Last updated
- 27 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30046155Lin 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.
PubMed 8223076Di 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.
PubMed 17151807Ido 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.
PubMed 30228265Machnicki 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.
PubMed 18644133Garvey 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.
PubMed 39318719
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Determine the Safety and Tolerability of Microbial Inulinase
- ClinicalTrials.gov ID
- NCT05744700
- Acronym / sponsor ID
- B03-22-01-T0037
- Conditions
- Digestive Health, Gastrointestinal Health
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- BIO-CAT, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
- Study start
- 28 Apr 2023 (actual)
- Primary completion
- 6 Oct 2023 (actual)
- Study completion
- 6 Oct 2023 (actual)
- First posted
- 27 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Dietary FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) can be digestively bothersome for certain fiber-intolerant individuals, as well as those with irritable bowel syndrome (Dionne et al.). Oral supplementation of microbial enzymes is a promising strategy to ameliorate gastrointestinal (GI) symptoms-such as bloating, abdominal discomfort, and gas-that are associated with food intolerances. Oral enzyme supplementation with fungal beta-galactosidase (lactase), fungal alpha-galactosidase, and a mixture of microbial and plant proteases have previously been clinically shown to effectively reduce GI symptoms associated with dairy, legume, and gluten consumption, respectively (Lin et al.; Di Stefano et al.; Ido et al.). While alpha-galactosidase effectively hydrolyzes galactan-type FODMAPs, there remains a need to target fructan-type FODMAPs. Preclinical data using an in vitro static GI digestion model showed that the microbial enzyme inulinase can effectively digest fructan-rich substrates (e.g., inulin from chicory root, garlic, and a high-fructan meal mash) better than control conditions under simulated gastric conditions (Guice et al., submitted).
The present study is a randomized, double-blind, placebo-controlled clinical trial to determine the safety and tolerability of microbial inulinase as a digestive enzyme supplement in healthy adults. This clinical trial will include 60 participants who are healthy adults between the ages of 20 to 60 and who regularly consume at least two meals daily. The study duration will be up to 62 days. This trial consists of one screening visit (Visit 1, Day -30 to -15), a baseline visit (Visit 2, Day 1), and an end-of-study visit (Visit 3, Day 29 ± 3).
To assess the effect of inulinase on GI-related symptoms, participants will fill out the paper Gastrointestinal Symptom Rating Scale (GSRS) on a weekly basis over the course of the study. The GSRS is a validated questionnaire containing 15 questions used to assess symptoms that are commonly associated with GI disorders (Machnicki et al.). All 15 questions are rated using a 7-point Likert scale, where higher ratings represent more discomfort. The GSRS score is determined by the score of five subscales: reflux, diarrhea, abdominal Pain, indigestion, and constipation. The reflux score will be calculated as an average score of questions 2 and 3. The diarrhea score will be calculated as an average score of questions 11,12, and 14. The abdominal pain score will be calculated as an average score of questions 1, 4, and 5. The indigestion score will be calculated as an average score of questions 6, 7, 8, and 9. The constipation score will be calculated as an average score of questions 10, 13, and 15. Each subscale score is the domain score. The average of all 5 domain scores will give the GSRS score. The GSRS score and 5 sub-scale (domain) scores will be used for analysis. The scores in Visit 2 will be treated as baseline, and change from baseline to Week 1, Week 2, Week 3, and Week 4 will be calculated, as well as the proportion of participants showing improved scores.
At screening Visit 1 (up to 30 days and no less than 15 days prior to the baseline visit), participants will arrive at the clinic in a fasting state (≥ 10 hours). After participants provide voluntary informed consent, the following information will be recorded, and procedures carried out:
- Collect demographic data (age, sex, ethnicity and race)
- Review medical/health history
- Review/record dietary and lifestyle habits
- Review/record use of concomitant treatments
- Review inclusion/exclusion criteria
- Take anthropometric measurements [height (screening only), weight) and vital signs [heart rate (HR) and blood pressure (BP)]
- Calculate body mass index (BMI; kg/m^2)
- Perform a brief symptom-based physical exam, if necessary
- Collect blood for hematology, clinical chemistry, lipid profile, and hemoglobin A1c (HbA1c)
- Dispense GSRS questionnaire for in-clinic completion
- Dispense GSRS questionnaire for at-home use
- Dispense study product (placebo only) and study diary
After confirming eligibility, from Day -14 to Day -1 (the day prior to baseline visit on Day 1), all participants will complete a 2-week run-in period where they will orally consume the placebo capsule twice daily with their usual two largest meals of the day (one capsule per meal) with the same two meals each day.
At baseline Visit 2 (Day 1), participants will arrive at the clinic in a fasting state (≥ 10 hours). The following visit procedures will occur:
- Collect and review any unused study product
- Review the study diary to assess compliance, concomitant treatments, medical conditions, and changes in health
- Review inclusion/exclusion criteria
- Review medical/health history
- Review any changes in dietary and lifestyle habits
- Take anthropometric measurements and vital signs (HR and BP)
- Calculate BMI using height collected from screening
- Collect blood for hematology, clinical chemistry, and lipid profiling
- Collect blood for lactate, insulin, uric acid, and high sensitivity C-reactive protein (hsCRP)
- Collect urine for pregnancy test
- Collect the GSRS questionnaire completed during the run-in period
- Dispense GSRS questionnaire for the participant to complete in-clinic
- Dispense GSRS questionnaire for at-home use
- Randomize the participant to inulinase or placebo
- Dose of study product in-clinic
- Adverse Event (AE) monitoring
- Dispense study products and study diary for home use by the participant
At the baseline visit on Day 1, participants will be randomized in a 1:1 ratio to either study product [1,000 units of inulinase activity (INU) per serving] or placebo and then start the 28 ± 3 days of twice daily study product consumption. Study product will be taken in the same manner (1 capsule taken twice daily with their two usual larger meals of the day).
At end-of-study Visit 3 (Day 29 ± 3), participants will arrive at the clinic in a fasting state (≥ 10 hours). The following visit procedures will occur:
- Return any unused study product and packaging of used study product
- Collect and review the study diary to assess compliance
- Review any changes in dietary and lifestyle habits
- Measure vital signs (BP and HR) and weight, and calculate BMI
- Collect urine for pregnancy test
- Collect blood for hematology, clinical chemistry, and lipid profiling
- Collect blood for lactate, insulin, uric acid, and hsCRP
- Collect the GSRS questionnaire and review for completion
- Dispense GSRS questionnaire for the participant to complete in-clinic
- AE monitoring
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inulinase | Active comparator | Dietary Supplement: InulinaseTotal 2,000 INU inulinase per day for 28 days |
| Placebo | Placebo comparator | Dietary Supplement: Maltodextrin placeboMaltodextrin for 28 days |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InulinaseAlso: Fructan hydrolyase, Beta-fructofuranosidaseParticipants 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. | Dietary supplement | Inulinase |
| Maltodextrin placeboParticipants will consume one capsule containing maltodextrin, twice daily, for 28 days. Participants will be directed to consume the capsules with their two largest meals. | Dietary supplement | Placebo |
Primary outcome
Gastrointestinal Symptom Rating Scale score
Time frame: 4 weeks
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.
Gastrointestinal Symptom Rating Scale improvement
Time frame: 4 weeks
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.
Abdominal discomfort, bloating, and burping scores
Time frame: 4 weeks
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.
Plasma lactate
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting plasma lactate concentration (mmol/L)
Serum insulin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum insulin concentration (pmol/L)
Serum uric acid
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum uric acid concentration (umol/L)
Serum high-sensitivity C-reactive protein (hsCRP)
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum hsCRP concentration (mg/L)
Serum total cholesterol
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total cholesterol concentration (mmol/L)
Serum low-density lipoprotein (LDL) cholesterol
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum LDL cholesterol concentration (mmol/L)
Serum high-density lipoprotein (HDL) cholesterol
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum HDL cholesterol concentration (mmol/L)
Plasma high-density lipoprotein (HDL) cholesterol
Time frame: 6 weeks
Between placebo and inulinase treatments, change from screening to Day 28 in fasting plasma HDL cholesterol concentration (mg/dL)
Serum triglycerides
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum triglycerides concentration (mmol/L)
Serum albumin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum albumin concentration (g/L)
Serum alkaline phosphatase
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alkaline phosphatase concentration (U/L)
Serum alanine transaminase
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum alanine transaminase concentration (U/L)
Serum aspartate transaminase
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum aspartate transaminase concentration (U/L)
Serum chloride
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum chloride concentration (mmol/L)
Serum creatinine
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum creatinine concentration (umol/L)
Serum globulin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum globulin concentration (g/L)
Serum glucose
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum glucose concentration (mmol/L)
Serum potassium
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum potassium concentration (mmol/L)
Serum sodium
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum sodium concentration (mmol/L)
Serum total bilirubin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total bilirubin concentration (umol/L)
Serum total protein
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting serum total protein concentration (g/L)
Whole blood basophils
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood basophil count (x 10^9/L)
Whole blood eosinophils
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood eosinophil count (x 10^9/L)
Whole blood hematocrit
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hematocrit (as volume percent)
Whole blood hemoglobin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood hemoglobin concentration (g/dL)
Whole blood lymphocytes
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood lymphocyte count (x 10^9/L)
Whole blood mean corpuscular hemoglobin
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular hemoglobin (pg)
Whole blood mean corpuscular hemoglobin concentration
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular hemoglobin concentration (g/L)
Whole blood mean corpuscular volume
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean corpuscular volume (fL)
Whole blood monocytes
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood monocyte count (x 10^9/L)
Whole blood neutrophils
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood neutrophil count (x 10^9/L)
Whole blood platelets
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood platelet count (x 10^9/L)
Whole blood mean platelet volume
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood mean platelet volume (fL)
Whole blood red blood cells
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood red blood cell count (x 10^9/L)
Whole blood red blood cell distribution width
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood red blood cell distribution width
Whole blood white blood cells
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in fasting whole blood white blood cell count (x 10^9/L)
Whole blood hemoglobin A1c (HbA1c)
Time frame: Day 1
Fasting whole blood HbA1c concentration at Day 1 (%)
Estimated glomerular filtration (eGFR)
Time frame: 4 weeks
Between placebo and inulinase treatments, change from baseline to Day 28 in eGFR (mL/min/1.73m^2)
Blood pressure
Time frame: 4 weeks
Resting systolic blood pressure over resting diastolic blood pressure (mmHg/mmHg)
Heart rate
Time frame: 4 weeks
Resting heart rate (beats per minute)
Body weight
Time frame: 4 weeks
Body weight (kg)
Body mass index
Time frame: 4 weeks
Body mass index (kg/m^2)
Incidence of adverse events
Time frame: 4 weeks
Number of participants with adverse events
Incidence of serious adverse events
Time frame: 4 weeks
Number of participants with serious adverse events
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2024.
- Background: PubMed 30046155Dionne 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.
- Background: PubMed 8223076Lin 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.
- Background: PubMed 17151807Di 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.
- Background: PubMed 30228265Ido 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.
- Background: PubMed 18644133Machnicki 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.
- Results publication: PubMed 39318719Garvey 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Bier, MD, CCFP principal investigator
Apex Trials
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Inulinase in people with Digestive Health and Gastrointestinal Health, run by BIO-CAT, Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gastrointestinal Symptom Rating Scale score (time frame: 4 weeks). The study lists 47 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05744700, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.