A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability

Stress, Psychological Clinical Trial

— HYPERNUTRI  

Official title:

A Nutritional Intervention to Prevent Stress Induced Intestinal Hyper-Permeability

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06089811
• Other study ID #: S66915
• Status: Recruiting
• Phase: N/A
• Start date: October 10, 2023
• Est. completion date: July 1, 2024

Study information

• Verified date: October 2023
• Source: KU Leuven
• Contact: Danique La Torre, MSc
• Phone: +3216373499
• Email: danique.latorre[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: July 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Stress, Psychological

Intervention

Dietary Supplement:
• Prebiotic
Group 1 (prebiotic and placebo L-tryptophan): prebiotic (oligofructose, Orafti®P95, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day)
• L-Tryptophan
Group 2 (placebo prebiotic and L-tryptophan): L-tryptophan (3g/day) and placebo prebiotic (microcrystalline cellulose, 20g/day)
• Placebo
Group 3 (placebo prebiotic and placebo L-tryptophan): placebo prebiotic (microcrystalline cellulose, 20g/day) and placebo L-tryptophan (microcrystalline cellulose, 3g/day).

Locations

Country	Name	City	State
Belgium	KU Leuven/ UZ Leuven	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intestinal permeability baseline	Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.	Measured 2 days before the pre-intervention and immediately after the 4 week intervention.
Other	Short chain fatty acids	Short chain fatty acids will be measured both in feces and serum.	Measured for 3h during the pre-intervention and immediately after the 4 week intervention.
Other	Tryptophan metabolites	Tryptophan metabolites (kynurenine and indole pathway) will be measured in urine and blood.	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.
Other	Inflammatory cytokines	Including interleukin (IL)-1ß, IL-6, IL-10, IL-13, interferon (IFN)-?, and tumor necrosis factor (TNF)-a	Measured at the pre-intervention and immediately after the 4 week intervention.
Other	Subjective pain response to the prolonged stress test	The subjective pain response to the prolonged stress task (Leuven Prolonged Stress Test) will be measured using a Visual Analogue Scale (VAS) (1-100)	Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Other	Cognitive reactivity to failure response to the prolonged stress test	Cognitive reactivity to failure response to the prolonged stress task (Leuven Prolonged Stress Test) will be assessed using two rating scales on a scale of 0 to 100. On one scale, 0 means 'I feel much less self-assured than before, 50 means 'I feel as self-assured as before, and 100 means 'I feel much more self-assured than before'. On the other scale, 0 means 'I think I'm not good at anything at all, 50 means 'I still think the same about myself', and 100 means 'I think I can achieve anything'.	Measured during the stress induction task during both the pre-intervention visit and immediately after the 4 week intervention.
Other	Perceived Stress Scale (PSS)	The Perceived Stress Scale (PSS) is a 14-item instrument designed to measure the degree to which situations in one's life are appraised as stressful. It provides a tool for examining issues about the role of appraised stress levels in the etiology of disease and behavioral disorders. The scale is designed such that it asks the respondent to rate the frequency of his/her feelings and thoughts related to events and situations that occurred over a selected time-frame. Notably, high PSS scores have been correlated with higher biomarkers of stress, such as cortisol.	Measured at the pre-intervention and immediately after the 4 week intervention.
Other	Gastrointestinal symptom rating scale (GSRS)	The Gastrointestinal Symptom Rating Scale (GSRS) is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The reliability and validity of the GSRS are well-documented, and norm values for a general population are available.	Measured at the pre-intervention and immediately after the 4 week intervention.
Other	Patient Health Questionnaire 9 (PHQ-9)	The Patient Health Questionnaire - 9 (PHQ-9) is a 9-item questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This self-report measure determines the severity of depression symptoms and is frequently used to monitor changes in symptom severity over time in non-psychiatric settings. Subjects are asked to rate each of the items on a scale of 0 to 3 on the basis of how much a symptom has bothered them over the last 2 weeks (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day).	Measured at the pre-intervention and immediately after the 4 week intervention.
Other	Generalized Anxiety Questionnaire 7 (GAD-7)	The Generalized Anxiety Questionnaire (GAD-7) is a 7-item questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This self-report measure reflects the frequency of anxiety symptoms over the past 2 weeks. Subjects are asked to rate each of the items on a scale of 0 to 3 on the basis of how much a symptom has bothered them over the last 2 weeks (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day).	Measured at the pre-intervention and immediately after the 4 week intervention.
Primary	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	Intestinal permeability after a prolonged stress task (the Leuven Prolonged Stress Test)	Intestinal permeability will be measured using the lactulose-mannitol test. The lactulose-mannitol ratio will be calculated and used as a measure for small intestinal permeability. Fractional excretion of lactulose and mannitol will also be assessed.	Measured at the pre-intervention and immediately after the 4 week intervention.
Secondary	Stress response to a prolonged stress test (the Leuven Prolonged Stress Test)	Cortisol, blood pressure, and subjective stress. Cortisol will be measured in saliva. Subjective stress will be measured using a Visual Analogue Scale (VAS)	During the stress task (at multiple time points during 120 min), measured at the pre-intervention and immediately after the 4 week intervention.