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RECRUITING

NCT07713641

Short-Chain Fatty Acids in Lypopolysaccharide-Induced Inflammation and Executive Function

Sponsor: Universitaire Ziekenhuizen KU Leuven

View on ClinicalTrials.gov

Summary

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.

Official title: Investigating the Role of Short-Chain Fatty Acids in Endotoxemia-Induced Inflammation and Core Executive Functioning: A Randomized, Triple-Blind, Placebo-Controlled Trial

Key Details

Gender

All

Age Range

18 Years - 45 Years

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-10-24

Completion Date

2027-03-30

Last Updated

2026-07-20

Healthy Volunteers

Yes

Conditions

Endotoxemia Inflammation Executive Function (Cognition)

Interventions

DIETARY_SUPPLEMENT

Short-Chain Fatty Acid Colon-Delivery Capsules

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.

DIETARY_SUPPLEMENT

Placebo capsules

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.

BIOLOGICAL

Lipopolysaccharide (LPS)

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.

Inclusion Criteria: * Voluntary written informed consent obtained prior to any study procedure * Healthy, with no gastrointestinal or psychological complaints * Age 18-45 years * BMI 18.5-27 kg/m2 * Proficiency in English and/or Dutch Exclusion Criteria: * History of previous or current neurological disorder (e.g., epilepsy, multiple sclerosis, migraine with aura) * History of previous or current psychiatric disorder (e.g., depression, anxiety disorders, bipolar disorder, schizophrenia) * History of previous or current gastrointestinal disorder (e.g., Crohn's disease, ulcerative colitis, irritable bowel syndrome) * History of previous or current endocrine disorder (e.g., diabetes, thyroid disorders, polycystic ovary syndrome) * History of immune system disorder, including inflammatory, autoimmune, or severe allergic conditions (e.g., rheumatoid arthritis, lupus, celiac disease, or severe allergies such as anaphylaxis) * History of neuropsychiatric disorder (e.g., ADHD, autism spectrum disorder, learning disorder, Tourette's syndrome) * History of major head trauma (e.g., concussion with loss of consciousness or long-term symptoms) * History of severe infection (e.g., sepsis, pneumonia requiring hospitalization, meningitis, endocarditis, or other systemic infection requiring hospitalization, intravenous antibiotics, or intensive care) * One or more diagnoses based on the Mini International Neuropsychiatric Interview (MINI) * One or more diagnoses based on ROME-IV criteria for gastrointestinal disorders * Any disorder that, in the investigator's opinion, might jeopardise the participant's safety or compliance with the protocol * Any prior or concomitant treatment that might jeopardise the participant's safety or compromise the integrity of the study * Participation in an interventional trial with an investigational medicinal product (IMP) or device * Current or recent (past month) prescribed medication use, with particular attention to cardiovascular drugs, steroids, NSAIDs, and centrally-acting drugs (excluding isolated over-the-counter use such as ibuprofen or paracetamol, and hormonal contraceptives in women) * Use of psychotropic medication within the past year (e.g., antidepressants, anxiolytics, antipsychotics) * Use of antibiotics within three months preceding the study * Use of pre- or probiotics within one month preceding the study * Current or recent (past month) infection (e.g., common cold, influenza, COVID-19) * Recent (past month) vaccination * Pregnant or lactating women * Previous or current substance or alcohol dependence or abuse (\>2 units/day or \>14 units/week) * Smoking * Night-shift work * Adherence to special diets (e.g., vegan, vegetarian, weight-loss, lactose-free, gluten-free) * Previous experience with or knowledge of any of the cognitive tasks used in the study (questionnaires excluded) * C-reactive protein higher than 0.5mg/dL on the day of the injection. * Colour vision deficiency or colour-blindness

Locations (1)

University Hospital Leuven (UZ Leuven)

Leuven, Belgium