Brain Responses to Short-Chain Fatty Acid Intervention

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Short-Chain Fatty Acids
  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
• Другое Placebo
  Microcrystalline Cellulose will be used as placebo, one daily, one week

Первичные конечные точки

• HDAC expression [Срок оценки: Throughout study completion, on average 2 years]
• Brain response to stress [Срок оценки: Throughout study completion, on average 2 years]

Вторичные конечные точки (9)

• Brain metabolite concentration [Срок оценки: Throughout study completion, on average 2 years]
• Serum short-chain fatty acid levels [Срок оценки: Throughout study completion, on average 2 years]
• Salivary cortisol response to stress [Срок оценки: Throughout study completion, on average 2 years]
• Cytokine levels [Срок оценки: Throughout study completion, on average 2 years]
• C-reactive protein levels [Срок оценки: Throughout study completion, on average 2 years]
• Heart rate variability [Срок оценки: Throughout study completion, on average 2 years]
• Blood pressure [Срок оценки: Throughout study completion, on average 2 years]
• Heartbeat [Срок оценки: Throughout study completion, on average 2 years]
• Self-reported stress [Срок оценки: Throughout study completion, on average 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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")

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Бельгия · 1 центр

• UZ/KU Leuven — Leuven

Идентификаторы

NCT: NCT06546683 · S68154

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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