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NCT Number: NCT06546683

Brain Responses to Short-Chain Fatty Acid Intervention

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.

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Key information

Age range

18 year–45 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

UZ/KU Leuven

Leuven, 3000, Belgium

Location contact

Lukas Van Oudenhove, MD, PhD

CONTACT

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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")

Treatment and study plan

Short-Chain Fatty Acids

Other

Colon-delivery capsules of Short-Chain Fatty Acids will be administered in a ratio of 60:20:20, thus 150 mmol of acetate, 50 mmol of propionate and 50 mmol of butyrate equivalent to 20g of fibers, once daily, one week

Placebo

Other

Microcrystalline Cellulose will be used as placebo, one daily, one week

Primary outcomes

  1. HDAC expression

    Time frame: Throughout study completion, on average 2 years

    Brain HDAC expression will be quantified using the PET radiotracer [11C]Martinostat before and after the intervention

  2. Brain response to stress

    Time frame: 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 outcomes

  1. Brain metabolite concentration

    Time frame: Throughout study completion, on average 2 years

    Relative quantification of brain metabolites (mmol/L) using 1H-Magnetic Resonance Spectroscopy before and after intervention

  2. Serum short-chain fatty acid levels

    Time frame: Throughout study completion, on average 2 years

    Quantification of serum SCFA (μM) before and after intervention

  3. Salivary cortisol response to stress

    Time frame: 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

  4. Cytokine levels

    Time frame: Throughout study completion, on average 2 years

    Quantification of inflammatory cytokines (pg/ml) before and after intervention

  5. C-reactive protein levels

    Time frame: Throughout study completion, on average 2 years

    Quantification of hs-C-reactive protein levels (ng/ml) before and after intervention

  6. Heart rate variability

    Time frame: Throughout study completion, on average 2 years

    Assessing heart rate variability (ms) with ECG before and after intervention

  7. Blood pressure

    Time frame: Throughout study completion, on average 2 years

    Assessing blood pressure (systolic/diastolic mmHg) with a blood pressure monitor before and after intervention

  8. Heartbeat

    Time frame: Throughout study completion, on average 2 years

    Assessing heartbeat (bpm) with a blood pressure monitor before and after intervention

  9. Self-reported stress

    Time frame: 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.

Other outcomes

  1. Fecal gut microbiota profile

    Time frame: Throughout study completion, on average 2 years

    Assessing gut microbiota profile before and after intervention

  2. Perceived Stress Scale (PSS)

    Time frame: Throughout study completion, on average 2 years

    Assessing ratings on PSS. PSS scores range between 0-40 with higher scores indicating worse outcome

  3. Gastrointestinal Symptom Rating Scale (GSRS)

    Time frame: Throughout study completion, on average 2 years

    Assessing ratings on the subscales of GSRS and its total score. It has 5 subscales (Reflux, Diarrhea, Constipation, Abdominal Pain, and Indigestion Syndrome). Subscale scores range from 1 to 7 and higher scores indicates a worse outcome.

  4. Big Five Inventory 10 (BFI-10)

    Time frame: Throughout study completion, on average 2 years

    Measuring the Big Five personality traits, including Extraversion, Agreeableness, Conscientiousness, Emotional Stability, and Openness.

  5. Generic Assessment of Side Effects

    Time frame: Throughout study completion, on average 2 years

    General side effects will be assessed and recorded in a structured, validated approach using the Generic Assessment of Side Effects (GASE)54. The GASE consists of 36 items asking for most frequently reported side effects for drugs based on the FDA adverse event reporting system database from all countries. Symptoms of all body parts during the last seven days will be self-reported and rated based on severity from 0 (not present) to 3 (severe).

  6. State-Trait-Anxiety Inventory (STAI)

    Time frame: Throughout study completion, on average 2 years

    Assessing momentary (state) anxiety during the pre- and post-intervention visit. This inventory is part of the State-Trait Anxiety Inventory (STAI) with 20 questions specifically for state anxiety, rated on a 4-point scale. State anxiety is rated with anxiety absent and anxiety present questions. Anxiety absent questions constitute the absence of anxiety in a statement like, "I feel secure." Anxiety present questions represent the presence of anxiety in a statement like "I feel worried." The 4-point scale are as follows: 1 'not at all', 2 'somewhat', 3 'moderately so', and 4 'very much so'.

  7. Emotion Regulation Questionnaire (ERQ)

    Time frame: Throughout study completion, on average 2 years

    designed to assess individual differences in the habitual use of two emotion regulation strategies: cognitive reappraisal and expressive suppression

  8. Pittsburgh Sleep Quality Index (PSQI)

    Time frame: Throughout study completion, on average 2 years

    an instrument to measure the quality and patterns of sleep in adults. . It differentiates "poor" from "good" sleep by measuring seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month.

  9. The Cognitive Assessment Questionnaire (CAQ)

    Time frame: Throughout study completion, on average 2 years

    to assess the frequency with which people experience cognitive failures, such as absent-mindedness, in everyday life - slips and errors of perception, memory and motor functioning. The questionnaire has 25 items which are scored from Never (0), Very rarely (1), Occasionally (2), Quite often (3) to Very often (4). A total score as well as three subscales (Forgetfulness, Distractibility, False Triggering) can be calculated.

  10. Mainz Inventory for Microstressors (MIMIS)

    Time frame: Throughout study completion, on average 2 years

    retrospective assessment of microstressors over one week covering both stressor occurence and perceived stressor intensity

Study contacts

Contact information is provided by the study sponsor or research team.

Lukas Van Oudenhove, MD, PhD

CONTACT

[email protected]

+32 16 33 01 47

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Registry information

Official study title

The Effect of a Short-Chain Fatty Acid Intervention on Affective Brain Circuits and Neuroepigenetics

Acronym: MoodBugs HDAC

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Aug 9, 2024
Registry last updated
Aug 9, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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