PRObiotic and Stress-related PERmeability (ProSPer)

The Effect of a Probiotic Strain on Stress-related Intestinal Hyperpermeability in Adult Humans.

This is a single-site exploratory study aiming to demonstrate the effect of a fresh fermented dairy drink containing a probiotic strain on stress-related intestinal hyperpermeability in students defending a bachelor's or master's thesis in front of a jury at the University of Leuven (Belgium).

Study Overview

• Status: Completed
• Conditions: Permeability; Increased
• Intervention / Treatment: Dietary supplement: Fresh fermented dairy drink containing probiotic strain; Other: Acidified dairy drink without ferment

Detailed Description

The study is conceived as a single-site exploratory study with a randomized, controlled, parallel group design. There will be a double blind with 2 intervention arms (Test product with probiotic and acidified milk Control) plus an extra open label arm without intervention in a 2:2:1 ratio. The goal of the open-label arm is to confirm our previous data on the effect of stress on small intestinal permeability (see reference), without powering the study to detect a significant difference within this open-label arm. The participants and the investigators are blinded to the allocation to the probiotic vs. acidified milk control arm. However, there is no blinding in the arm without intervention.

In vivo intestinal permeability and salivary markers of psychological stress and activation of the autonomous nervous system will be measured and questionnaires will be completed at 4 different test days: baseline (V2), two weeks after randomization (V3), during an oral defense of a master's or bachelor's thesis (V4) and finally after pretreatment with Indomethacin (V5).

The 5 study visits are organized around the thesis defence (D0):

V1 (screening + inclusion) takes place within 2 to 3 weeks prior to the randomization.

V2 (baseline + randomization) will take place between D-35 to D-27. V3 (randomization + 2 weeks) will take place at D-14 +/-1day. V4 (thesis defense) is D0 and organized by the University. V5 (Indomethacin) will take place at D+14 +/-1day.

For subjects in the intervention arm (Test product with probiotic and acidified milk Control), products will be supplied (for 1 week). In addition, alternate product supply will take place at D-21, D-7 and D+7 (each one +/-1day).

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Belgie
    • Leuven, Belgie, Belgium, 3000
      • KU Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Student defending a bachelor's or master's thesis in front of a jury
• Age 20 till 30 years (both included), both genders
• Subject, upon briefing of the content of the present study, fully understanding and agreeing to its objective and having given written (dated and signed) informed consent form to take part in the study
• Subject willing to consume 2 units of investigational product per day during the investigational product consumption period.
• For females: If of child bearing potential, female subjects must be using or complying with methods of contraception
• Subject willing to strictly follow dietary/medication instructions for the entire duration of the study
• Subject must have access to a refrigerator with adequate space to store the investigational products according to the labels' storage recommendations and a freezer for the cooling elements in the transport bag

Exclusion Criteria:

• Subject with chronic gastrointestinal disorders or symptoms, type 1 or type 2 diabetes mellitus, psychiatric disease including but not limited to depression (screened by PHQ-9) and general anxiety disorder (screened by GAD-7), celiac disease, food allergy or a history of atopic conditions (eczema, allergic asthma, allergic rhinoconjunctivitis) requiring active treatment
• Subject with allergy or intolerance to non-steroidal anti-inflammatory drugs (NSAID)
• Subject with first degree relatives with coeliac disease, inflammatory bowel disease (IBD) or type 1 diabetes
• Subject with known or suspected lactose intolerance or suspected allergy or hypersensitivity to any component of the study product(s) (e.g. milk protein)
• Subject receiving (currently or in the 2 last weeks) systemic treatment or topical treatment likely to interfere with evaluation of the study parameters: antibiotics, intestinal or respiratory antiseptics, anti-rheumatics, NSAIDs and steroids prescribed in chronic inflammatory diseases.
• Active smoker with at least 7 cigarettes per week
• Subject consuming regularly (>1/week) more than 3 units of alcohol per day.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Test product; Fresh fermented dairy drink containing probiotic strain consumed as follows: one bottle (100g) BID for 6 weeks	Dietary supplement: Fresh fermented dairy drink containing probiotic strain; Fresh fermented dairy drink containing probiotic strain consumed as follows: one bottle (100g) BID for 6 weeks.
Placebo Comparator: Control product; Acidified dairy drink without ferment consumed as follows: one bottle (100g) BID for 6 weeks	Other: Acidified dairy drink without ferment; Acidified dairy drink without ferment consumed as follows: one bottle (100g) BID for 6 weeks.
No Intervention: No product; no product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactulose-Mannitol Ratio (LMR) during the stress condition vs. baseline	LMR or in vivo small intestinal permeability during stress condition vs. baseline in the Test product with probiotic compared to the acidified milk Control arm	oral administration of Test or Control product for 4 weeks before stress condition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LMR during administration of Test or Control product vs. baseline	LMR or in vivo small intestinal permeability during administration vs. baseline within each intervention arm and between groups.	oral administration of Test or Control product for 2 weeks
LMR after indomethacin vs. baseline	LMR or in vivo small intestinal permeability after indomethacin vs. baseline within each intervention arm and between groups	oral administration of Test or Control product for 6 weeks before indomethacin
Salivary cortisol during the stress condition vs. baseline	Salivary cortisol during the stress condition vs. baseline within each intervention arm and between groups	oral administration of Test or Control product for 4 weeks before stress condition
Subjective anxiety levels (STAI state) during the stress condition vs. baseline	Subjective anxiety levels (STAI state) during the stress condition vs. baseline within each intervention arm and between groups	oral administration of Test or Control product for 4 weeks before stress condition

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Tim Vanuytsel, MD PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, Salim Rasoel S, Tomicronth J, Holvoet L, Farre R, Van Oudenhove L, Boeckxstaens G, Verbeke K, Tack J. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014 Aug;63(8):1293-9. doi: 10.1136/gutjnl-2013-305690. Epub 2013 Oct 23.
• Wauters L, Van Oudenhove L, Accarie A, Geboers K, Geysen H, Toth J, Luypaerts A, Verbeke K, Smokvina T, Raes J, Tack J, Vanuytsel T. Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial. Gut Microbes. 2022 Jan-Dec;14(1):2031695. doi: 10.1080/19490976.2022.2031695.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Actual): March 22, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 17, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Actual): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: probiotic; stress; permeability
• Other Study ID Numbers: S60969

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
• product manufactured in and exported from the U.S.: No