An interventional study of Short-Chain Fatty Acid Colon-Delivery Capsules and Placebo capsules in Endotoxemia, Inflammation and Executive Function (Cognition), sponsored by Universitaire Ziekenhuizen KU Leuven. Recruiting at 1 site in Belgium. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-20.
Sponsored by Universitaire Ziekenhuizen KU Leuven · Not applicable, Interventional, and Basic science
Short-chain fatty acids (SCFAs) are substances produced by gut bacteria when they ferment dietary fiber. They can act as signals between the gut and the brain and may help regulate the body's immune and stress responses. Earlier work has shown that delivering SCFAs to the colon can lower the stress hormone response to a mental stress task in healthy people, and laboratory studies suggest SCFAs can reduce inflammation. However, it is not yet known whether SCFAs can reduce inflammation in humans, or whether doing so protects mental performance.
This study uses a controlled, acute, and short-lasting challenge. Healthy adults receive a single, low dose of a bacterial substance called lipopolysaccharide (LPS) through a vein. LPS briefly activates the immune system and causes mild, flu-like symptoms (such as fatigue, headache, and feeling unwell) that pass on their own within a few hours. It does not cause a real infection.
Participants are randomly assigned to take either SCFA capsules or inactive placebo capsules on the morning of the test day, before the LPS challenge. Neither the participants, the researchers running the visit, nor the researchers analyzing the results know who received which capsules until the study is complete (triple-blind).
The main goal of the study is to test whether SCFAs, compared with placebo, reduce the inflammatory response to LPS, measured by markers of inflammation in the blood. The study also examines whether SCFAs reduce the associated sickness symptoms and whether they protect performance on tasks that measure core executive functions: the ability to keep relevant information in mind (working memory), the ability to hold back automatic responses or thoughts (inhibition), and the ability to switch flexibly between tasks or rules (cognitive flexibility). Blood, saliva, and stool samples are collected to measure inflammation markers, SCFA levels, stress hormones, and gut bacteria.
Participants attend a screening visit, a test day with monitoring for several hours, and a short follow-up visit the next day.
INFLEX is a single-center, randomized, triple-blind, placebo-controlled, parallel-group interventional trial conducted at UZ Leuven / KU Leuven. Its primary aim is to test whether a single acute dose of colon-delivered SCFAs, relative to placebo, attenuates the systemic inflammatory response induced by experimental endotoxemia in healthy adults. Secondary aims are to test whether SCFAs attenuate LPS-induced sickness behaviour and mitigate endotoxemia-induced changes in core executive functioning, and to characterize associations between systemic SCFA uptake, the inflammatory response, and these outcomes.
Eligible participants are randomized to receive SCFA colon-delivery capsule or placebo capsules, taken on the morning of the test day with a standardized low-fiber breakfast. One hour after capsule intake, participants receive a single intravenous bolus of purified Escherichia coli lipopolysaccharide (0.4 ng/kg body weight), which serves as a fixed inflammatory challenge applied to all participants. The timing is designed so that peak circulating SCFA concentrations (approximately 3-4 hours after colonic delivery) coincide with the peak of LPS-induced cytokines and sickness behaviour (approximately 2-3 hours post-injection).
Participants are monitored for a minimum of 6 hours after the LPS challenge. Vital signs, sickness symptoms, and blood and saliva samples are collected hourly to quantify inflammatory markers (including IL-6 and hs-CRP), serum SCFA, cortisol, and ACTH. Core executive-function tasks are administered before and after the LPS challenge and at a 24-hour follow-up visit. A fecal sample collected at home prior to the test day is used for gut microbiota profiling. To standardize endogenous SCFA production, participants follow a low-fiber diet for three days before the test day and avoid caffeine, alcohol, and strenuous exercise beforehand. The night prior to the test day, participants are instructed to consume a standard dinner that is provided to them.
The study comprises three visits: a screening visit (\~1 hour), the laboratory test day (\~8 hours), and a follow-up visit (\~30 minutes) 24 hours after the LPS challenge.
81 studies on the registry are indexed under Endotoxemia; 7 are open to participants now.
This study's planned enrollment of 56 is above the median of 31 across 70 interventional studies indexed under Endotoxemia.
Browse Endotoxemia studies →Universitaire Ziekenhuizen KU Leuven is the lead sponsor of 963 studies on the registry; 267 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A single acute oral dose of colon-delivery capsules delivering a short-chain fatty acid mixture (approximately 186 mmol total SCFA: 111 mmol acetate, 43 mmol propionate, 32 mmol butyrate; molar ratio approximately 60:23:17), taken on the morning of the test day with a standardized low-fiber breakfast.
Dietary Supplement: Short-Chain Fatty Acid Colon-Delivery Capsules · Biological: Lipopolysaccharide (LPS)
Single acute oral dose of placebo capsules containing microcrystalline cellulose and matching excipients, matched in appearance and number to the SCFA capsules.
Dietary Supplement: Placebo capsules · Biological: Lipopolysaccharide (LPS)
Single acute oral dose of pH-dependent colon-delivery capsules delivering a short-chain fatty acid mixture to the colon. The mixture comprises sodium acetate,sodium butyrate, and sodium propionate (54.4%, 21.2%, and 24.4% by weight), providing approximately 186 mmol total SCFA per dose (111 mmol acetate, 32 mmol butyrate, 43 mmol propionate). Capsules are sub-coated with hydroxypropylcellulose and coated with a pH-dependent layer (Eudragit FS 30 D with PlasACRYL T20). Taken on the morning of the test day with a standardized low-fiber breakfast.
Single acute oral dose of placebo capsules containing microcrystalline cellulose and matching excipients, an inert non-fermentable substrate. Matched in appearance and number to the SCFA capsules and taken on the morning of the test day with a standardized low-fiber breakfast.
Also known as: Placebo, microcrystalline cellulose
Single intravenous bolus of purified Escherichia coli-derived lipopolysaccharide (0.4 ng/kg body weight), administered one hour after capsule intake to all participants as a standardized experimental inflammatory challenge common to both study arms.
Also known as: LPS, Endotoxin
Serum interleukin-6 (IL-6) response to the LPS challenge
Effect of SCFA versus placebo on the systemic inflammatory response to experimental endotoxemia, indexed by serum IL-6 concentrations measured at serial timepoints across the test day following the intravenous LPS bolus. The primary analysis evaluates the treatment-by-timepoint interaction on the IL-6 time course using a linear mixed model, with treatment (SCFA vs. placebo) as a between-subject factor and timepoint as a within-subject factor.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Serum pro- and anti-inflammatory cytokine response to the LPS challenge
Effect of SCFA versus placebo on serum concentrations of TNF-alpha, IL-1-beta, IFN-gamma, IL-8, IL-4, and IL-10. Analyzed as treatment-by-timepoint interactions using linear mixed models.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
High-sensitivity C-reactive protein (hs-CRP) response to the LPS challenge
Effect of SCFA versus placebo on serum high-sensitivity C-reactive protein (hs-CRP) concentrations, measured at selected timepoints on the test day and at the 24-hour follow-up visit.
Time frame: 2 hours before LPS injection, and at 2, 6, and 24 hours after LPS injection
LPS-induced sickness behaviour (SicknessQ)
Effect of SCFA versus placebo on subjective sickness behaviour, assessed with the Sickness Questionnaire (SicknessQ), analyzed across timepoints on the test day.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Body temperature response to the LPS challenge
Effect of SCFA versus placebo on body temperature (degrees Celsius).
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Heart rate response to LPS challenge
Effect of SCFA versus placebo on heart rate (beats per minute) across the monitoring period.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Blood pressure response to the LPS challenge
Effect of SCFA versus placebo on systolic and diastolic blood pressure (mmHg).
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Salivary cortisol response to the LPS challenge
Effect of SCFA versus placebo on salivary cortisol concentrations (ng/ml).
Time frame: At 0, 1, 2, 3, 4, and 6 hours after LPS injection
Plasma ACTH
Effect of SCFA versus placebo on plasma ACTH concentrations (ng/l)
Time frame: At 0, 1, 2, 3, 4, and 6 hours after LPS injection
Working memory performance (3-back task)
Effect of SCFA versus placebo on working memory, assessed with the 3-back task (primary index: d-prime). Assessed at baseline (pre-LPS), post-LPS on the test day, and at the 24-hour follow-up.
Time frame: 2 hours before LPS injection, 2.25 hours after LPS injection, and 24 hours after LPS injection
Response inhibition (Stop Signal Task)
Effect of SCFA versus placebo on response inhibition, assessed with the Stop Signal Task (outcome: stop-signal reaction time, SSRT, in milliseconds).
Time frame: 2 hours before LPS injection, 2.25 hours after LPS injection, and 24 hours after LPS injection
Cognitive flexibility - task switching (Number-Letter task)
Effect of SCFA versus placebo on cognitive flexibility, assessed with the Number-Letter task (outcome: switch cost, in milliseconds).
Time frame: 2 hours before LPS injection, 2.25 hours after LPS injection, and 24 hours after LPS injection
Cognitive inhibition (Stroop task)
Effect of SCFA versus placebo on cognitive inhibition, assessed with the Stroop task (outcome: congruency effect, in milliseconds).
Time frame: 2 hours before LPS injection, 2.25 hours after LPS injection, and 24 hours after LPS injection
Cognitive flexibility - set shifting (Wisconsin Card Sorting Task)
Effect of SCFA versus placebo on cognitive flexibility, assessed with the Wisconsin Card Sorting Task (outcome: number of perseverative errors).
Time frame: 2 hours before LPS injection, 2.25 hours after LPS injection, and 24 hours after LPS injection
Systemic SCFA uptake (serum SCFA concentrations)
Serum concentrations of acetate, propionate, and butyrate, assessed as a measure of systemic SCFA uptake to confirm target engagement of the colon-delivery intervention, and used as a mediator in mechanistic analyses of treatment effects on the inflammatory response.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, and 6 hours after LPS injection
Baseline gut microbiota composition
Baseline fecal gut microbiota composition, characterized by quantitative microbiome profiling from a single fecal sample collected before the test day. Examined in exploratory analyses as a baseline predictor of inter-individual variability in systemic SCFA uptake and treatment response.
Time frame: Single fecal sample collected within the 3 days prior to the test day
Mood - valence (MDMQ)
Effect of SCFA versus placebo on self-reported mood valence (good-bad dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate a more positive mood.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
Mood - alertness (MDMQ)
Effect of SCFA versus placebo on self-reported alertness (awake-tired dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate greater alertness.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
Mood - calmness (MDMQ)
Effect of SCFA versus placebo on self-reported calmness (calm-restless dimension), assessed with the Multidimensional Mood Questionnaire (MDMQ/MDBF). Score range 1-40; higher scores indicate greater calmness.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
Negative affect (PANAS)
Effect of SCFA versus placebo on self-reported negative affect, assessed with the negative affect subscale of the Positive and Negative Affect Schedule (10 items, 5-point Likert; score range 10-50). Higher scores indicate greater negative affect.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
Positive affect (PANAS)
Effect of SCFA versus placebo on self-reported positive affect, assessed with the positive affect subscale of the Positive and Negative Affect Schedule (10 items, 5-point Likert; score range 10-50). Higher scores indicate greater positive affect.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
State anxiety (STADI)
Effect of SCFA versus placebo on self-reported state anxiety, assessed with the anxiety subscale of the State-Trait Anxiety and Depression Inventory (STADI), state form (4-point Likert). Higher scores indicate greater state anxiety.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
State depression (STADI)
Effect of SCFA versus placebo on self-reported state depression, assessed with the depression subscale of the State-Trait Anxiety and Depression Inventory (STADI), state form (4-point Likert). Higher scores indicate greater state depressive symptoms.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
Sleepiness (SSS)
Effect of SCFA versus placebo on self-reported sleepiness, assessed with the Stanford Sleepiness Scale (single item, range 1-7). Higher scores indicate greater sleepiness.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
State anxiety (STAI-S)
Effect of SCFA versus placebo on self-reported state anxiety, assessed with the state subscale of the State-Trait Anxiety Inventory (20 items, 4-point Likert; score range 20-80). Higher scores indicate greater state anxiety.
Time frame: 2 hours before LPS injection, and at 0, 1, 2, 3, 4, 5, 6 and 24 hours after LPS injection
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