Brain Responses to Short-Chain Fatty Acid Intervention
- Conditions
- Healthy VolunteersStress
- Interventions
- Other: Short-Chain Fatty AcidsOther: Placebo
- Registration Number
- NCT06546683
- Lead Sponsor
- Universitaire Ziekenhuizen KU Leuven
- Brief Summary
A randomized, triple-blind, placebo-controlled study on the effect of colon-delivered short-chain fatty acids (SCFAs) on neural responses to stress and neuroepigenetics.
- Detailed Description
The goal of this interventional study is to study the underlying mechanism of the attenuating effect of colon-delivered SCFAs on the cortisol response to stress. Pre-clinical studies suggest that the histone-deacetylase (HDAC)-inhibiting properties of SCFAs are the main mechanism underlying SCFA-induced changes in stress, cognition and behavior.
Primary objective: to test the effect of colon-delivered SCFA intervention versus placebo on HDAC expression in the brain and neural responses to stress
Secondary objective: to determine the effects of colon-delivered SCFA administration versus placebo on inflammatory and autonomic responses to stress and to determine the mediating and/or moderating factors that potentially underlie SCFA-induced changes to stress responses (HDAC expression in stress-responsive regions, serum SCFA levels)
To this end, 32 participants will be asked to undergo a pre- and post-intervention visit, separated by one week intervention with either colon-delivered SCFAs or placebo (16 per group). During the study visits, participants undergo simultaneous PET-MR imaging with \[11C\]Martinostat. They undergo the Montreal Imaging Stress Test (MIST) and the Maastricht Acute Stress Test (MAST) at each visit.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 32
- Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
- Proficiency in English and/or Dutch
- Access to a -18°C freezer (i.e. ordinary household freezer)
- Male participants
- Age 18-45 years
- BMI 18.5-25 kg/m2
- Participant has a history of previous or current neurological, psychiatric, gastrointestinal or endocrine disorder
- Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol (as assessed by medical staff on the research team)
- Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the study
- Participation in an interventional Trial with an investigational medicinal product (IMP) or device
- Current or recent (3-month) medication use (especially antibiotics, cardiovascular drugs, steroids, non-steroid anti-inflammatory drugs, centrally effective drugs)
- Current or recent (1-month) infection (e.g. common cold, influenza, COVID-19, etc.)
- Recent (1-month) vaccination (e.g. flu shot, SARS-COV-2 vaccine, etc)
- Smoking
- Night-shift work
- Adherence to special diets (e.g. vegan, vegetarian, weight-loss, lactose-free, gluten- free, etc.)
- Use of pre- or probiotics within one month preceding the study
- Previous experience with any of the tasks used in the study (not including questionnaires)
- Neuroimaging contraindications
- If the participant invokes that he does not want to be informed of eventual pathology that might be found during imaging (invokes the "right not to know")
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Short-Chain Fatty Acids Short-Chain Fatty Acids SCFAs will be delivered directly to the colon using pH-dependent colon delivery capsules Placebo Placebo Colon-delivery capsules of microcrystalline cellulose
- Primary Outcome Measures
Name Time Method HDAC expression Throughout study completion, on average 2 years Brain HDAC expression will be quantified using the PET radiotracer \[11C\]Martinostat before and after the intervention
Brain response to stress Throughout study completion, on average 2 years Brain response (brain oxygenation level-dependent signals) to a fMRI-adapted stress task will be measured before and after intervention
- Secondary Outcome Measures
Name Time Method Salivary cortisol response to stress Throughout study completion, on average 2 years Biological stress sensitivity is measured by quantifying cortisol levels (ng/ml) from multiple saliva samples taken before, during, and after a stress task performed during the pre-intervention and post-intervention visit
C-reactive protein levels Throughout study completion, on average 2 years Quantification of hs-C-reactive protein levels (ng/ml) before and after intervention
Brain metabolite concentration Throughout study completion, on average 2 years Relative quantification of brain metabolites (mmol/L) using 1H-Magnetic Resonance Spectroscopy before and after intervention
Serum short-chain fatty acid levels Throughout study completion, on average 2 years Quantification of serum SCFA (μM) before and after intervention
Heart rate variability Throughout study completion, on average 2 years Assessing heart rate variability (ms) with ECG before and after intervention
Blood pressure Throughout study completion, on average 2 years Assessing blood pressure (systolic/diastolic mmHg) with a blood pressure monitor before and after intervention
Cytokine levels Throughout study completion, on average 2 years Quantification of inflammatory cytokines (pg/ml) before and after intervention
Heartbeat Throughout study completion, on average 2 years Assessing heartbeat (bpm) with a blood pressure monitor before and after intervention
Self-reported stress Throughout study completion, on average 2 years Psychological stress sensitivity is measured through stress reports of the participants using the visual analogue scale (VAS). VAS scorings are taken before, during, and after a stress task performed during the pre-intervention and post-intervention visit.
Trial Locations
- Locations (1)
UZ/KU Leuven
🇧🇪Leuven, Belgium