Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution

Study Overview
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Brief Summary
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Study objectives: Primary: Difference in breath hydrogen concentration (BHC, ppm) in lactase and probiotic groups compared to placebo, measured by the incremental area under curve (iAUC) analysis Non-inferiority in breath hydrogen concentration (BHC, ppm) of probiotic group compared to lactase group, measured by the incremental area under curve (iAUC) analysis Secondary: Breath test Breath hydrogen peak value (ppm) in lactase and probiotic groups compared to placebo Cumulative breath hydrogen (ppm) in lactase and probiotic groups compared to placebo Acute gastrointestinal symptoms (severity or presence/absence to be defined on a Likert scale) in lactase and probiotic groups compared to placebo Abdominal pain Flatulence Bloating Nausea and vomiting Bowel movements and diarrhea (if present, stool consistency to be defined on Bristol stool scale and number of bowel movements to be recorded) Ancillary: Baseline fasting BHC (ppm) Breath methane CH4 (ppm) Breath carbon dioxide CO2 (ppm) Probiotic identification in feces before each lactose challenge by molecular methods Gene test to determine lactase deficiency status at screening (following SNP variants to be screened: 13910*C (Europe, Central Asia, commonly used) -22018*G (Europe), -13915*T (Saudi-Arabia, Africa), -14010*G (Africa), -13907*C (Africa))

Official Title
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Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution: Randomized, Double-blind, Placebo-controlled, Positive-controlled, Three-way Crossover, Acute Lactose Challenge

Conditions
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Lactose Intolerance

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Dietary Supplement: Lactase
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary, written, informed consent to participate in the study Agreement to comply with the protocol and study restrictions Healthy females and males of age 25 to 60 years (inclusive) Self-declared, suspected or medically diagnosed lactose intolerance Increase of more than 20 ppm in breath hydrogen within 3 h from the baseline fasting breath hydrogen value Participants who agree to maintain their usual dietary habits throughout the trial period Participants who agree not to consume probiotics, prebiotics, fermented milk, and/or yogurt containing probiotics during the intervention period (Visits 3-5) and two weeks before Visit 3 (2 weeks after screening visit) Females of child-bearing potential who agree to use a medically approved method of birth control Ability of the participant (in the investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research Exclusion Criteria: Gastrointestinal disorder or disease (e.g. Crohn's disease, ulcer, irritable bowel syndrome (IBS), Celiac disease, small intestinal bacterial overgrowth (SIBO), pancreatitis and disorders affecting gastrointestinal motility) Diagnosed type 1 or type 2 diabetes Prior abdominal surgery that, in the opinion of the investigator, may present a risk for the participant or affect study results Ongoing or recent (last 1 month) antibiotic treatment. Use of laxatives or drugs known to affect gut motility 1 month preceding the screening visit and during the study Ongoing or recurrent use of proton pump inhibitors Colonoscopy within 3 months before screening History of recurrent colon cleansing and/or a colon cleansing within 3 months before screening Gastrointestinal infection within 1 month before screening or during the trial Clinically significant underlying systemic illness that may preclude the participant's ability to complete the trial or that may affect the study outcomes (e.g. bowel cancer, prostate cancer, terminal illness) History of diagnosed coronary heart disease/cardiovascular disease or artificial heart valve Any obstructive or restrictive respiratory syndrome/disease that may impact breath test (e.g. asthma or chronic obstructive pulmonary disease (COPD)) Regular use of tobacco, snuff, nicotine and e-cigarette, and possible other inhaled products. Light smokers (less than 5 cigarettes per day) who agree not to smoke during the whole duration of the study may be included. Self-declared history of alcohol abuse (for females: >3 drinks on any single day and >7 drinks per week; for males: >4 drinks on any single day and >14 drinks per week) Self-declared use of illicit drugs within 4 weeks preceding the screening visit Pregnant or lactating female, or pregnancy planned during study period Participants under administrative or legal supervision. Participation in another study with any investigational product within 60 days of screening Clinically significant abnormal values in safety blood tests at screening Other reasons that, in the opinion of the Investigator, make the participant unsuitable for enrolment Who would receive more than 4500€ as indemnities for his participation in biomedical research within the last 12 months, including the indemnities for the present study.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic powder<br>One sachet of Probiotic powderwill be consumed with 25 g lactose in 250 ml of water in the beginning of a 6-hour challenge at the study visits. | Dietary Supplement: Probiotic<br>* Intake of probiotic<br>|
| Active Comparator: Lactase<br>One sachet of Lactase powder will be consumed with 25 g lactose in 250 ml of water in the beginning of a 6-hour challenge at the study visits. | Dietary Supplement: Lactase<br>* Intake of lactase<br>|
| Placebo Comparator: Placebo<br>One sachet of placebo powder will be consumed with 25 g lactose in 250 ml of water in the beginning of a 6-hour challenge at the study visits. | Other: Placebo<br>* Intake of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo | Difference in breath hydrogen concentration (BHC, ppm) in probiotic compared to placebo, measured by the iAUC analysis | During the 6-hour acute lactose challenge | 
| Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo | Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by the iAUC analysis | During the 6-hour acute lactose challenge | 
| Non-inferiority in breath hydrogen concentration (BHC, ppm) of probiotic group compared to lactase group (positive control) | Non-inferiority in breath hydrogen concentration (BHC, ppm) of probiotic group compared to lactase group (positive control), measured by the iAUC analysis | During the 6-hour acute lactose challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by breath hydrogen peak value | Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by breath hydrogen peak value | During the 6-hour acute lactose challenge | 
| Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by breath hydrogen peak value | Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by breath hydrogen peak value | During the 6-hour acute lactose challenge | 
| Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by cumulative breath hydrogen value | Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by cumulative breath hydrogen value | During the 6-hour acute lactose challenge | 
| Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by cumulative breath hydrogen value | Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by cumulative breath hydrogen value | During the 6-hour acute lactose challenge | 
| Difference in the severity of abdominal pain in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of abdominal pain in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of abdominal pain in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of abdominal pain in probioticgroup compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of flatulence in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of flatulence in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of flatulence in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of flatulence in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of bloating in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of bloating in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of bloating in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of bloating in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of nausea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of nausea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the severity of nausea in probioticgroup compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the severity of nausea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of vomiting in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of vomiting in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of vomiting in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of vomiting in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of bowel movements in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of bowel movements in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of bowel movements in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of bowel movements in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of diarrhea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of diarrhea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge | 
| Difference in the presence of diarrhea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | Difference in the presence of diarrhea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey | During the 6-hour acute lactose challenge |