Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Fat-free Milk

Gastrointestinal Symptoms Clinical Trial

Official title:

Effect of Probiotic Supplementation on Lactose Maldigestion Induced by Fat-free Milk: Randomized, Double-blind, Placebo-controlled, Crossover, Acute Lactose Challenge

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03659747
• Other study ID #: NH-03977
• Status: Completed
• Phase: N/A
• Start date: September 11, 2018
• Est. completion date: December 21, 2018

Study information

• Verified date: March 2019
• Source: Danisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the study is to investigate the effect of probiotic supplementation on lactose maldigestion.

Description:

Primary endpoint is defined as the difference in breath hydrogen concentration (BHC, ppm) in lactase and probiotic groups compared to placebo and non-inferiority in breath hydrogen concentration (BHC, ppm) in probiotic group compared to lactase group, measured by the incremental area under curve (iAUC) analysis.

To characterize the benefit of the investigational product (IP) the following secondary endpoints will be analyzed:

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 V1 (following single nucleotide polymorphism (SNP) variants to be screened: -13910*C (Europe, Central Asia, commonly used) -13915*T (Saudi-Arabia, Africa), -14010*C (Africa), -13907*C (Africa))

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 21, 2018
• Est. primary completion date: December 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 60 Years

Eligibility

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 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 at V2

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 and two weeks before Visit 3 (2 weeks after pre-screening visit)

8. Females of child-bearing potential who agree to use a medically approved methods 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 months) 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. Use of tobacco, snuff, nicotine and e-cigarette

14. History of or current abuse of drugs, alcohol or medication (self- reported)

15. Self-declared use of illicit drugs

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. Abnormal values in safety blood tests at V1 i.e. clinically significant or >2x upper limit of normal, unless the deviation is justified by a previously known not clinically relevant condition (e.g. Gilbert's syndrome)

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

Related Conditions & MeSH terms

• Breath Test
• Gastrointestinal Symptoms

Intervention

Dietary Supplement:
• Probiotic
- 6 g sachet containing probiotic powder (1.8 x 10^12 CFU Probiotic) in sachet - One sachet of the investigational product will be consumed with 521 ml of Weihenstephan fat-free milk once in the beginning of a 6-hour challenge at a study visit.
• Lactrase
- 6 g sachet containing 4500 Food Chemical Codex (FCC) units of lactase (Lactrase, Oy Verman Ab, Kerava, Finland) and maltodextrin as a carrier - One sachet of the investigational product will be consumed with 521 ml of Weihenstephan fat-free milk once in the beginning of a 6-hour challenge at a study visit.

Other:
• Placebo
- 6 g sachet containing placebo powder (maltodextrin) in sachet - One sachet of the investigational product will be consumed with 521 ml of Weihenstephan fat- free milk once in the beginning of a 6-hour challenge at a study visit.

Locations

Country	Name	City	State
Germany	analyze & realize GmbH	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Danisco	Analyze & Realize

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Difference in baseline fasting BHC (ppm) between the treatments		approximately 40 days
Other	Difference in breath methane concentration (ppm) between the treatments		approximately 40 days
Other	Difference in breath carbon dioxide concentration (ppm) between the treatments		approximately 40 days
Other	Difference in the quantity of probiotic in fecal samples between the treatments		approximately 40 days
Other	Description of the SNP variants in each treatment group		approximately 40 days
Primary	Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by the iAUC analysis		approximately 40 days
Primary	Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by the iAUC analysis		approximately 40 days
Primary	Non-inferiority in breath hydrogen concentration (BHC, ppm) of probiotic group compared to lactase group (positive control), measured by the iAUC analysis		approximately 40 days
Secondary	Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by breath hydrogen peak value		approximately 40 days
Secondary	Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by breath hydrogen peak value		approximately 40 days
Secondary	Difference in breath hydrogen concentration (BHC, ppm) in lactase group compared to placebo, measured by cumulative breath hydrogen value		approximately 40 days
Secondary	Difference in breath hydrogen concentration (BHC, ppm) in probiotic group compared to placebo, measured by cumulative breath hydrogen value		approximately 40 days
Secondary	Difference in the presence of diarrhea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the presence of diarrhea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of abdominal pain in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of abdominal pain in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of flatulence in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of flatulence in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of bloating in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of bloating in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of nausea in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the severity of nausea in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the presence of vomiting in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the presence of vomiting in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the presence of bowel movements in lactase group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days
Secondary	Difference in the presence of bowel movements in probiotic group compared to placebo, as defined by the gastrointestinal symptom survey		approximately 40 days