The primary objective of this study is to investigate the effect of an oral probiotic (Bacillus sp. spore preparation) on abdominal bloating, flatulence, and burping in generally healthy adults. Secondary outcomes include intestinal barrier integrity and fecal microbiome properties (taxonomical structure, diversity, and function).
Probiotics are live microbes that, when administered in adequate amounts, confer a health benefit. Examples of probiotic health benefits include the support of gastrointestinal (GI) health and immune health. Common probiotic strains include species from the Bacillaceae family (e.g. Bacillus genus) and Lactobacillaceae family of the Bacillota phylum (formerly Firmicutes), and species from the Bifidobacterium genus of the Actinomycetota phylum (formerly Actinobacteria). Bacillaceae species are particularly advantageous for oral probiotic applications because they can be manufactured as spores with highly proteinaceous coats that persist without refrigeration and resist the acidic and high bile salt conditions that occur across the human GI tract. The objective of this clinical study is to investigate the effects of daily oral supplementation with a novel Bacillus sp. spore preparation for 8 weeks on GI symptoms, intestinal barrier integrity, and fecal microbiome properties. This will be a randomized, parallel, double-blind, placebo-controlled study consisting of one screening visit (Visit 1, Day -7) and four study visits (Days 0, 1, 57, and 58). At Visit 1 (Day -7), participants will arrive at the clinic in a fasting state (≥ 10 hours). After participants provide voluntary informed consent, participants will undergo medical history, prior and current medication/supplement use, and inclusion and exclusion criteria assessments. Additionally, height, body weight, and vital signs will be measured, and body mass index (BMI) will be calculated. Blood samples will be collected for chemistry, hematology, C-reactive protein (CRP), and insulin analyses. Participants will be dispensed a daily paper Gastrointestinal Tolerance Questionnaire (GITQ) with instructions to capture events occurring during the seven continuous days prior to Visit 2 (Day 0). The paper GITQ contains a series of questions regarding the presence and severity of GI symptoms occurring during the past 24 hours. Therefore, participants will be instructed to complete their first GITQ on the morning of Day -6 and the final GITQ on the morning of Day 0, just before their Visit 2. Additionally, a stool sample collection kit will be dispensed with instructions to a collect stool sample from a single bowel movement (for fecal microbiome analyses) within the 3 days immediately before Visit 2 (Day 0). At Visit 2 (Day 0), participants will arrive at the clinic in a fasting state (≥ 10 hours). Participants will undergo clinic visit procedures (concomitant medication/supplement use, assess inclusion/exclusion criteria, body weight, and vital signs measurements) and adverse event (AE) assessment. Fecal samples will be collected, and subjects will be administered a 7-day recall GITQ. Participants will then undergo an intestinal permeability test where they will ingest four sugar probes (1 g mannitol, 1 g sucralose, 1 g erythritol, and 5 g lactulose) in approximately 240 mL water. Participants will be dispensed 2 separate containers to collect all urine over the following 24 hours, with urine collected from 0 to 5 hours in one container and from 5 to 24 hours in the second container. Participants will be instructed to return both containers to the clinic the following day at Visit 3 (Day 1). Upon completion of the GI permeability test, participants will be randomly assigned to a study product sequence. Participants will receive an email link for an electronic 7-day recall GITQ to be completed on Days 8, 15, 22, 29, 36, 43, 50, and 57. Participants will also receive information regarding daily links that will be sent via email to complete electronic 24-hour recall GITQs and will be instructed to complete these electronic 24-hour GITQs daily starting on day 51, which will be 6 days ahead of Visit 4. Participants will continue recording the 24-hour GITQ recall every day for seven total days (Days 51, 52, 53, 54, 55, 56, and 57). Additionally, a stool sample collection kit will be dispensed with instructions to collect a stool sample from a single bowel movement for fecal microbiome analyses within the 3 days immediately before Visit 4 (Day 57). In addition, a subset of male subjects will be selected to collect an additional fecal sample for fecal metabolomic and/or targeted analyte analyses. At Visit 3 (Day 1), participants will return the 24-hour urine sample collection containers and undergo AE assessments. Participants will be dispensed their assigned study product and will be instructed to consume it once a day (1 capsule/d) with their meal that is typically the largest of the day for 56 days starting on Day 1. At Visit 4 (Day 57), participants will arrive at the clinic fasted (≥ 10 hours) and undergo clinic visit procedures, including: concomitant medication/supplement use, review inclusion/exclusion criteria, body weight and vital signs measurements, and AE assessment. Fecal samples will be collected. Blood samples will be collected for chemistry, hematology, CRP, and insulin analyses. Participants will then complete the intestinal permeability test with the same procedures and study instructions described at Visit 2. At Visit 5 (Day 58), participants will return the 24-hour urine sample collection containers and undergo AE assessments.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
80
Biofortis Clinical Research, Inc.
Addison, Illinois, United States
Composite score of abdominal bloating, flatulence, and burping (daily GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease (indicating improvement) in the 7-day total composite score of abdominal bloating, flatulence, and burping, from baseline to week 8, where an increase in scores (indicating worsening) cannot occur within any of the 3 symptoms (daily Gastrointestinal Tolerance Questionnaire \[GITQ\])
Time frame: 9 weeks
Composite score of abdominal bloating, flatulence, and burping (7-day recall GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease in the 7-day total composite score of abdominal bloating, flatulence, and burping, from baseline to week 8 (7-day recall GITQ)
Time frame: 9 weeks
Composite score of 8 GI symptoms (daily GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease in the 7-day total composite score of abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux, from baseline to week 8 (daily GITQ)
Time frame: 9 weeks
Composite score of 8 GI symptoms (7-day recall GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease in the 7-day total composite score of abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux, from baseline to week 8 (7-day recall GITQ)
Time frame: 9 weeks
Individual GI symptom scores (daily GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease in 7-day individual symptom scores from baseline to week 8, for each of abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux (daily GITQ)
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Time frame: 9 weeks
Individual GI symptom scores (7-day recall GITQ)
Between placebo and probiotic treatments, the difference in the proportion of participants with a decrease in 7-day individual symptom scores from baseline to week 8, for each of abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux (7-day recall GITQ)
Time frame: 9 weeks
Composite score of abdominal bloating, flatulence, and burping (interim weeks)
Between placebo and probiotic treatments, the difference in the proportion of participants showing a decrease in the 7-day total composite score of abdominal bloating, flatulence, and burping, from baseline to each measured, interim time point (i.e., week 1, week 2, week 3, week 4, week 5, week 6, week 7) (7-day recall GITQ)
Time frame: 2 - 8 weeks
Individual GI symptom scores (interim weeks)
Between placebo and probiotic treatments, the difference in the proportion of participants showing a decrease in the 7-day individual symptom scores for each of abdominal bloating, flatulence, burping, nausea, vomiting, abdominal cramping, stomach rumbling, and reflux, from baseline to each measured, interim time point (i.e., week 1, week 2, week 3, week 4, week 5, week 6, week 7) (7-day recall GITQ)
Time frame: 2 - 8 weeks
Small intestinal permeability
Between placebo and probiotic treatments, the difference in small intestinal permeability from baseline to Day 57 (0 to 5 hour urinary lactulose:mannitol ratio)
Time frame: 8 weeks
Colonic permeability
Between placebo and probiotic treatments, the difference in colonic permeability from baseline to Day 57 (5 to 24 hour urinary sucralose:erythritol ratio)
Time frame: 8 weeks
Gut permeability
Between placebo and probiotic treatments, the difference in gut permeability from baseline to Day 57 (0 to 24 hour urinary sucralose:erythritol ratio)
Time frame: 8 weeks
Fecal microbiome profile
Between placebo and probiotic treatments, the difference in "shotgun" metagenomic sequencing-based fecal microbiome profiles from baseline to Day 57
Time frame: 8 weeks
Fecal microbiome profile
Between placebo and probiotic treatments, the difference in "shotgun" metagenomic sequencing-based fecal microbiome profiles at end of study
Time frame: Day 57
Plasma C-reactive protein
Between placebo and probiotic treatments, change from baseline to week 8 in fasting blood C-reactive protein concentration (mg/L)
Time frame: 9 weeks
Serum insulin
Between placebo and probiotic treatments, change from baseline to week 8 in fasting serum insulin concentration (mIU/L)
Time frame: 9 weeks
Safety: Albumin
Fasting plasma albumin concentration (g/dL)
Time frame: 9 weeks
Safety: Alkaline phosphatase
Fasting plasma alkaline phosphatase concentration (U/L)
Time frame: 9 weeks
Safety: Alanine aminotransferase
Fasting plasma alanine aminotransferase concentration (U/L)
Time frame: 9 weeks
Safety: Anion gap
Fasting plasma anion gap (nmol/L)
Time frame: 9 weeks
Safety: Aspartate aminotransferase
Fasting plasma aspartate aminotransferase concentration (U/L)
Time frame: 9 weeks
Safety: Blood urea nitrogen
Fasting blood urea nitrogen concentration (mg/dL)
Time frame: 9 weeks
Safety: Osmolality
Fasting plasma osmolality (mOsm/kg)
Time frame: 9 weeks
Safety: Calcium
Fasting plasma total calcium concentration (mg/dL)
Time frame: 9 weeks
Safety: Chloride
Fasting plasma chloride concentration (mmol/L)
Time frame: 9 weeks
Safety: Carbon dioxide
Fasting plasma carbon dioxide concentration (mmol/L)
Time frame: 9 weeks
Safety: Creatinine
Fasting plasma creatinine concentration (mg/dL)
Time frame: 9 weeks
Safety: Globulin
Fasting plasma globulin concentration (g/dL)
Time frame: 9 weeks
Safety: Glucose
Fasting plasma glucose concentration (mg/dL)
Time frame: 9 weeks
Safety: Potassium
Fasting plasma potassium concentration (mmol/L)
Time frame: 9 weeks
Safety: Sodium
Fasting plasma sodium concentration (mmol/L)
Time frame: 9 weeks
Safety: Total bilirubin
Fasting plasma total bilirubin concentration (mg/dL)
Time frame: 9 weeks
Safety: Total protein
Fasting plasma total protein concentration (g/dL)
Time frame: 9 weeks
Safety: Basophils
Fasting plasma basophil count
Time frame: 9 weeks
Safety: Eosinophils
Fasting plasma eosinophil count
Time frame: 9 weeks
Safety: Hematocrit
Fasting hematocrit (as volume percent)
Time frame: 9 weeks
Safety: Hemoglobin
Fasting plasma hemoglobin concentration (g/dL)
Time frame: 9 weeks
Safety: Lymphocytes
Fasting plasma lymphocyte count
Time frame: 9 weeks
Safety: Mean corpuscular hemoglobin
Fasting plasma mean corpuscular hemoglobin (pg)
Time frame: 9 weeks
Safety: Mean corpuscular hemoglobin concentration
Fasting plasma mean corpuscular hemoglobin concentration (g/dL)
Time frame: 9 weeks
Safety: Mean corpuscular volume
Fasting plasma mean corpuscular volume (fL)
Time frame: 9 weeks
Safety: Monocytes
Fasting plasma monocyte count
Time frame: 9 weeks
Safety: Neutrophils
Fasting plasma neutrophil count
Time frame: 9 weeks
Safety: Platelets
Fasting plasma platelet count
Time frame: 9 weeks
Safety: Red blood cells
Fasting plasma red blood cell count
Time frame: 9 weeks
Safety: White blood cells
Fasting plasma white blood cell count
Time frame: 9 weeks
Safety: Blood pressure
Resting systolic blood pressure over resting diastolic blood pressure (mmHg/mmHg)
Time frame: 9 weeks
Safety: Heart rate
Resting heart rate (beats per minute)
Time frame: 9 weeks
Safety: Incidence of adverse events
Number of participants with self-reported adverse events
Time frame: 9 weeks