A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability

NCT06089811 | Unknown

• 1 other identifier: S66915
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The interaction between the gut microbiome, the intestinal barrier, and the host plays an important role in human health. The integrity of the intestinal barrier is essential to protect against translocation of food antigens and immunostimulatory microbial metabolites from the gut lumen. Accumulating studies show that stress may negatively affect the intestinal barrier function. In a previous study, the investigators developed the Leuven Prolonged Acute Stress Test (L-PAST), which combines physical (cold water), mental (arithmetic), and social (negative feedback) aspects of stress for a prolonged (2h) time. In the current study the investigators would like, as a first aim, to investigate whether the L-PAST 1) increases intestinal permeability compared to baseline intestinal permeability, and 2) whether a nutritional intervention can improve baseline intestinal permeability as well as intestinal permeability after exposure to the L-PAST in both healthy females and men. As a second aim of the present study, the investigators would like to investigate whether prebiotics and/or L-tryptophan can attenuate the cortisol response to stress. Lastly, as acute psychosocial stress impairs cognitive functions, the investigators would like as a third aim to investigate whether prebiotics and/or L-tryptophan supplementation may prevent these impairments.

Conditions

Stress, Psychological

Outcome Measures

Primary Outcomes (1)

• Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)

  Working memory, cognitive flexibility, and response inhibition. Working memory will be assessed using the forward digit span. Cognitive flexibility will be assessed using the Wisconsin Card Sorting Test. Response inhibition will be assessed using the Stop Signal Task.

  Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.

Secondary Outcomes (2)

• Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)

  Measured at the pre-intervention and immediately after the 4 week intervention.

• Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)

  During the stress task (at multiple time points during 120 min), measured at the pre-intervention and immediately after the 4 week intervention.

Other Outcomes (10)

• Intestinal permeability baseline

  Measured 2 days before the pre-intervention and immediately after the 4 week intervention.

• Short chain fatty acids

  Measured for 3h during the pre-intervention and immediately after the 4 week intervention.

• Tryptophan metabolites

  Measured in blood for 3h during the pre-intervention and immediately after the 4 week intervention. Urine will be collected 3 days prior to the pre-intervention and immediately after the 4 week intervention.

Study Arms (3)

Prebiotic

EXPERIMENTAL

Dietary Supplement: Prebiotic

L-Tryptophan

EXPERIMENTAL

Dietary Supplement: L-Tryptophan

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Prebiotic DIETARY_SUPPLEMENT

Group 1 (prebiotic and placebo L-tryptophan): prebiotic (oligofructose, Orafti®P95, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day)

Prebiotic

L-Tryptophan DIETARY_SUPPLEMENT

Group 2 (placebo prebiotic and L-tryptophan): L-tryptophan (3g/day) and placebo prebiotic (microcrystalline cellulose, 20g/day)

L-Tryptophan

Placebo DIETARY_SUPPLEMENT

Group 3 (placebo prebiotic and placebo L-tryptophan): placebo prebiotic (microcrystalline cellulose, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day).

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 till 40 years (both included)
• BMI range: 18.5 - 25 kg/m²
• Females: Use of contraceptives, and have to use the current contraceptive method for at least 4 months. A regular menstrual cycle (between 25 and 35 days; if not using oral contraceptives)
• Subject is willing to not consume caffeine, or alcohol, to refrain from smoking, and not to engage in heavy physical exercise three days before the test days, as well as to not consume dairy products and chewing gum the day before and the day of the test days
• Subject is willing to not take any non-steroidal anti-inflammatory drugs (NSAIDs) two weeks before the test days (see Appendix G for an overview of NSAIDs)
• Subject, upon briefing of the content of the present study, fully understands and agrees to its objective and has given written (dated and signed) informed consent form to take part in the study
• Subject is able to communicate well with the investigator and follow instructions given by the investigator

You may not qualify if:

• Subject has a previous or current neurological, psychiatric, gastrointestinal, or endocrine disorder, or other relevant medical history
• Subject has one or more diagnoses based on the MINI international neuropsychiatric interview
• Subject has one or more diagnoses based on the ROME-IV for GI disorders
• Subject uses regular medication (i.e., anti-allergy medication, PPI's, and medication that can affect gut motility), currently or recently (in the last 2 weeks) (except for oral contraceptives)
• Subject has used recreational drugs in the past 6 months
• Subject consumes regularly (\>1/week) more than 3 units of alcohol per day
• Subjects smokes \>7 cigarettes per week
• Subject has to work in night-shifts
• Subject is pregnant or lactating
• Subject has previous experience with the stress test used in the study
• Subject has taken prebiotics or probiotics in the last month
• Subject has taken antibiotics in the last 3 months
• Subjects consumes \>25g of fiber per day in their habitual diet

Sponsors & Collaborators

• KU Leuven: lead

Study Sites (1)

KU Leuven/ UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

MeSH Terms

Conditions

Stress, Psychological

Interventions

Prebiotics; Tryptophan

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Dietary Supplements; Food and Beverages; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Central Study Contacts

Danique La Torre, MSc

CONTACT

+3216373499; danique.latorre@kuleuven.be

Kristin Verbeke, PhD

CONTACT

+3216330150; kristin.verbeke@kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, investigators, and personnel involved in data analyses are blinded to the intervention. Unblinding occurs after all data has been collected AND analysed.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: The present study is a parallel group randomized controlled trial (RCT) aiming to investigate whether two nutritional interventions (prebiotics and L-tryptophan) can improve intestinal barrier function, attenuate the stress response, affect cognitive processes, and prevent stress-induced hyperpermeability. Participants will perform 2 study visits of 3h each and with 28 days in between, in which participants will be subjected to the L-PAST. During the L-PAST, 3 cognitive tasks will be administered. Moreover, participants will be asked to take a basal intestinal permeability test at home 2 days before the test days.

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 18, 2023
• Study Start: October 10, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: October 18, 2023

Record last verified: 2023-10

Locations

BE (1)