Clinical trial NCT06546683: Brain Responses to Short-Chain Fatty Acid Intervention
Official title: The Effect of a Short-Chain Fatty Acid Intervention on Affective Brain Circuits and Neuroepigenetics
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stress
Healthy Volunteers
Keywords: Short-Chain Fatty Acids
Acute Stress
Microbiota-Gut-Brain-Axis
Neuroepigenetics
[11C] Martinostat
Functional magnetic resonance imaging
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2024-08-09
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Proficiency in English and/or Dutch
3. Access to a -18°C freezer (i.e. ordinary household freezer)
4. Male participants
5. Age 18-45 years
6. BMI 18.5-25 kg/m2

Exclusion Criteria:

1. Participant has a history of previous or current neurological, psychiatric, gastrointestinal or endocrine disorder
2. 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)
3. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the study
4. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
5. Current or recent (3-month) medication use (especially antibiotics, cardiovascular drugs, steroids, non-steroid anti-inflammatory drugs, centrally effective drugs)
6. Current or recent (1-month) infection (e.g. common cold, influenza, COVID-19, etc.)
7. Recent (1-month) vaccination (e.g. flu shot, SARS-COV-2 vaccine, etc)
8. Smoking
9. Night-shift work
10. Adherence to special diets (e.g. vegan, vegetarian, weight-loss, lactose-free, gluten- free, etc.)
11. Use of pre- or probiotics within one month preceding the study
12. Previous experience with any of the tasks used in the study (not including questionnaires)
13. Neuroimaging contraindications
14. 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")

Primary outcomes:
measure: HDAC expression
timeFrame: Throughout study completion, on average 2 years
measure: Brain response to stress
timeFrame: Throughout study completion, on average 2 years
Secondary outcomes:
measure: Brain metabolite concentration
timeFrame: Throughout study completion, on average 2 years
measure: Serum short-chain fatty acid levels
timeFrame: Throughout study completion, on average 2 years
measure: Salivary cortisol response to stress
timeFrame: Throughout study completion, on average 2 years
measure: Cytokine levels
timeFrame: Throughout study completion, on average 2 years
measure: C-reactive protein levels
timeFrame: Throughout study completion, on average 2 years
measure: Heart rate variability
timeFrame: Throughout study completion, on average 2 years
measure: Blood pressure
timeFrame: Throughout study completion, on average 2 years
measure: Heartbeat
timeFrame: Throughout study completion, on average 2 years
measure: Self-reported stress
timeFrame: Throughout study completion, on average 2 years
Other outcomes:
measure: Fecal gut microbiota profile
timeFrame: Throughout study completion, on average 2 years
measure: Perceived Stress Scale (PSS)
timeFrame: Throughout study completion, on average 2 years
measure: Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: Throughout study completion, on average 2 years
measure: Big Five Inventory 10 (BFI-10)
timeFrame: Throughout study completion, on average 2 years
measure: Generic Assessment of Side Effects
timeFrame: Throughout study completion, on average 2 years
measure: State-Trait-Anxiety Inventory (STAI)
timeFrame: Throughout study completion, on average 2 years
measure: Emotion Regulation Questionnaire (ERQ)
timeFrame: Throughout study completion, on average 2 years
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Throughout study completion, on average 2 years
measure: The Cognitive Assessment Questionnaire (CAQ)
timeFrame: Throughout study completion, on average 2 years
measure: Mainz Inventory for Microstressors (MIMIS)
timeFrame: Throughout study completion, on average 2 years
Locations:
city: Leuven
country: Belgium
facility: UZ/KU Leuven
Study officials:
affiliation: KU Leuven
name: Lukas Van Oudenhove, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Annalena Fuchs, MSc
role: STUDY_DIRECTOR
affiliation: KU Leuven
name: Kristin Verbeke, Pharm, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: KU Leuven
name: Boushra Dalile, PhD
role: PRINCIPAL_INVESTIGATOR
References: