The Effect of Probiotic Intake on Intestinal Permeability in Healthy Adults (PIP)

The Effect of Probiotic Intake on Intestinal Permeability of Healthy Adults

In this double blind, crossover study participants will take a placebo for 3 weeks each. Gut permeability will be assessed weekly using food-grade sugar molecules. On the second week, participants will take aspirin, which will make their intestine permeable to the sugars. Participants will be asked to provide urine and stool samples to assess gut permeability and microbial communities. No change in permeability to the small sugar probes is anticipated with the probiotic.

Study Overview

• Status: Completed
• Conditions: Intestinal Barrier Function
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611-0370
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Healthy individuals, aged 21 to 50 years who have ≥6 stools/week.
2. Willing to discontinue the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, aspirin, naproxen, or indomethacin, for the full length of the study.
3. Willing to avoid beer, wine, and cocktails on the day before and the day of the sugar probe tests. The sugar probe tests are visits 2, 3, 4, 6, 7, and 8.
4. Willing to avoid the use of antidiarrheal or laxative medication on a regular or an "as-needed basis" during the full length of the study.
5. Willing to provide urine and stool samples during the study collection periods.
6. Have used aspirin in the past and did not experience adverse effects.
7. Willing to consume three tablets (325 mg each or 975 mg total) twice within a 9 to 12-hour period. This challenge will be repeated twice during the 14-week study.
8. Willing to complete online questionnaires, records, and diaries associated with the study and to complete all clinic visits.
9. Willing to discontinue consumption of fermented foods or probiotics.
10. Willing to discontinue taking prebiotic, herbal, or high-dose vitamin or mineral supplements that may impact immune function or inflammation during the pre-baseline period and throughout the study protocol.
11. Willing to avoid high intensity exercises two days prior to and the day of the permeability tests. These tests will be done on six occasions.
12. Willing and able to consume the probiotic and placebo daily for 3 weeks each.
13. Willing and able to complete the informed consent form in English.
14. Willing to provide a social security number to receive study payment.

Exclusion Criteria

1. History or current impaired cardiovascular circulation or uncontrolled hypertension, diabetes, bleeding tendencies, kidney, liver or chronic respiratory diseases including asthma, gastrointestinal disorders including heartburn, or any other disease, that by the investigators discretion could interfere with the intestinal barrier function of the subject.
2. Daily use of NSAIDs in the last 3 months or incidental use in the last 2 weeks prior to screening.
3. Use of medications in the last 2 weeks prior to the pre-baseline period. This does not include birth control pills or standard multi-vitamin/mineral supplements.
4. Allergy to aspirin, milk, yeast, or soy.
5. Known sensitivity to gluten.
6. Current smokers.
7. Women who are lactating, know that they are pregnant, or are attempting to get pregnant.
8. Use of another investigational product within 3 months of the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Probiotic; 2 capsules daily for 3 weeks, containing 3.8 x 10^9 CFU (colony forming units)/capsule of Lactobacillus rhamnosus strain R011and 0.2 x 10^9 CFU/capsule of L. helveticus strain R0052 (group is unknown, double blinded)	Dietary supplement: Probiotic; This probiotic is commercially available and contains L. helveticus R0052 (0.2 x 10^9 CFU/capsule) and L. rhamnosus R0011 (3.8 x 10^9 CFU/capsule) as active ingredients and ascorbic acid, hypromellose, magnesium stearate, saccharose, potato starch, titanium dioxide, and maltodextrin as excipients.; Other Names: Lacidofil STRONG
PLACEBO_COMPARATOR: Placebo; 2 capsules daily for 3 weeks containing the same carrier material and is similar in size, shape and taste to probiotic (group is unknown, double blinded)	Dietary supplement: Placebo; The placebo contains ascorbic acid, hypromellose, magnesium stearate, saccharose, potato starch, titanium dioxide and maltodextrin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastroduodenal Permeability	The primary outcome is the difference between the changes in gastroduodenal permeability induced by aspirin challenge with the probiotic versus the placebo. Gastroduodenal permeability will be assessed while on the placebo and probiotic interventions by measuring urinary sucrose in the 0 to 5-hour urine collection of the sugar probe permeability test. Change will be calculated as the urinary sucrose concentration after aspirin challenge (week 2 of each intervention) minus the concentration from the prior week (i.e., 1 wk on intervention with no aspirin challenge).	Week 2 of each intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Small Intestinal Permeability	Difference between the changes (week 2 of intervention with aspirin minus week 1 of intervention without aspirin) in urinary lactulose/rhamnose ratio in the 0 to 5-hour urine collection with the probiotic versus the placebo interventions.	Weeks 1 and 2 on intervention
Colonic Permeability	Difference between the changes (week 2 of intervention with aspirin minus week 1 of intervention without aspirin) in sucralose/erythritol ratio in the 5 to 24-hour urine collection with the probiotic versus the placebo interventions.	Weeks 1 and 2 on intervention
Whole Gut Permeability	difference in the changes (week 2 of intervention with aspirin minus week 1 of intervention without aspirin) in sucralose/erythritol ratio in the 0 to 24-hour urine collection with the probiotic versus the placebo interventions	Weeks 1 and 2 on each intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Digestive Health	Weekly GI symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS). The GSRS consists of 15 questions related to 5 syndromes, constipation, diarrhea, reflux, abdominal pain, and indigestion. Symptoms are scored 1=no discomfort to 7=very severe discomfort. Scores from each of the 15 questions are summed for the total GSRS score.	Weekly through the completion of the 14 week study

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Lallemand Health Solutions

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 22, 2018
• Primary Completion (ACTUAL): April 15, 2019
• Study Completion (ACTUAL): April 15, 2019

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (ACTUAL): August 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Probiotic; Intestinal Permeability; Leaky Gut
• Other Study ID Numbers: IRB201800616; OCR18441 (OTHER: University of Florida)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No