Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution
Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution
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))
Inclusion Criteria:

 1. Voluntary, written, informed consent to participate in the study

 2. Agreement to comply with the protocol and study restrictions

 3. Healthy females and males of age 25 to 60 years (inclusive)

 4. Self-declared, suspected or medically diagnosed lactose intolerance

 5. Increase of more than 20 ppm in breath hydrogen within 3 h from the baseline fasting
 breath hydrogen value

 6. Participants who agree to maintain their usual dietary habits throughout the trial
 period

 7. 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)

 8. Females of child-bearing potential who agree to use a medically approved method of
 birth control

 9. 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

 10. Covered by Health Insurance System and / or in compliance with the recommendations of
 National Law in force relating to biomedical research

 Exclusion Criteria:

 1. 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)

 2. Diagnosed type 1 or type 2 diabetes

 3. Prior abdominal surgery that, in the opinion of the investigator, may present a risk
 for the participant or affect study results

 4. Ongoing or recent (last 1 month) antibiotic treatment.

 5. Use of laxatives or drugs known to affect gut motility 1 month preceding the screening
 visit and during the study

 6. Ongoing or recurrent use of proton pump inhibitors

 7. Colonoscopy within 3 months before screening

 8. History of recurrent colon cleansing and/or a colon cleansing within 3 months before
 screening

 9. Gastrointestinal infection within 1 month before screening or during the trial

 10. 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)

 11. History of diagnosed coronary heart disease/cardiovascular disease or artificial heart
 valve

 12. Any obstructive or restrictive respiratory syndrome/disease that may impact breath
 test (e.g. asthma or chronic obstructive pulmonary disease (COPD))

 13. 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.

 14. 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)

 15. Self-declared use of illicit drugs within 4 weeks preceding the screening visit

 16. Pregnant or lactating female, or pregnancy planned during study period

 17. Participants under administrative or legal supervision.

 18. Participation in another study with any investigational product within 60 days of
 screening

 19. Clinically significant abnormal values in safety blood tests at screening

 20. Other reasons that, in the opinion of the Investigator, make the participant
 unsuitable for enrolment

 21. 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.