Clinical trial NCT06089811: A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability
Official title: A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stress, Psychological
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2023-10-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Executive functions during a prolonged stress task (the Leuven Prolonged Stress Test)
timeFrame: Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Secondary outcomes:
measure: Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
measure: Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)
timeFrame: 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:
measure: Intestinal permeability baseline
timeFrame: Measured 2 days before the pre-intervention and immediately after the 4 week intervention.
measure: Short chain fatty acids
timeFrame: Measured for 3h during the pre-intervention and immediately after the 4 week intervention.
measure: Tryptophan metabolites
timeFrame: 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.
measure: Inflammatory cytokines
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
measure: Subjective pain response to the prolonged stress test
timeFrame: Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
measure: Cognitive reactivity to failure response to the prolonged stress test
timeFrame: Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
measure: Perceived Stress Scale (PSS)
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
measure: Gastrointestinal symptom rating scale (GSRS)
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
measure: Patient Health Questionnaire 9 (PHQ-9)
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
measure: Generalized Anxiety Questionnaire 7 (GAD-7)
timeFrame: Measured at the pre-intervention and immediately after the 4 week intervention.
Locations:
city: Leuven
country: Belgium
facility: KU Leuven/ UZ Leuven
state: Vlaams-Brabant
Study officials:
References: