Clinical trial NCT03814668: Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution
Official title: Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Lactose Solution: Randomized, Double-blind, Placebo-controlled, Positive-controlled, Three-way Crossover, Acute Lactose Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Lactose Intolerance
Lead sponsor: Danisco
Sponsor class: INDUSTRY
First posted: 2019-01-24
Enrollment: 34
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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))


Eligibility criteria: 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.

Primary outcomes:
measure: Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo
timeFrame: During the 6-hour acute lactose challenge
measure: Non-inferiority in breath hydrogen concentration (BHC, ppm) of probiotic group compared to lactase group (positive control)
timeFrame: During the 6-hour acute lactose challenge
Secondary outcomes:
measure: Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by breath hydrogen peak value
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by breath hydrogen peak value
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by cumulative breath hydrogen value
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by cumulative breath hydrogen value
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of abdominal pain in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of abdominal pain in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of flatulence in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of flatulence in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of bloating in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of bloating in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of nausea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the severity of nausea in probioticgroup compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of vomiting in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of vomiting in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of bowel movements in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of bowel movements in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of diarrhea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the presence of diarrhea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey
timeFrame: During the 6-hour acute lactose challenge
Other outcomes:
measure: Difference in baseline fasting BHC (ppm) between the treatments
timeFrame: Baseline
measure: Difference in breath methane concentration (ppm) between the treatments
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in breath carbon dioxide concentration (ppm) between the treatments
timeFrame: During the 6-hour acute lactose challenge
measure: Difference in the quantity of probiotic in fecal samples between the treatments
timeFrame: 48-hours before the visits
measure: Description of the SNP variants in each treatment group
timeFrame: At screening
Locations:
city: Gières
country: France
facility: Eurofins Optimed
Study officials:
References:
citation: Rasinkangas P, Forssten SD, Marttinen M, Ibarra A, Bothe G, Junnila J, Uebelhack R, Donazzolo Y, Ouwehand AC. Bifidobacterium animalis subsp. lactis Bi-07 supports lactose digestion in vitro and in randomized, placebo- and lactase-controlled clinical trials. Am J Clin Nutr. 2022 Dec 19;116(6):1580-1594. doi: 10.1093/ajcn/nqac264.