The Effect of a Short-Chain Fatty Acid Intervention on Affective Brain Circuits and Neuroepigenetics
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- HDAC expression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Participants, investigators, and personnel involved in data analyses are blinded to the intervention. Unblinding occurs after all data has been collected and analysed.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
- •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")
研究组 & 干预措施
Short-Chain Fatty Acids
SCFAs will be delivered directly to the colon using pH-dependent colon delivery capsules
干预措施: Short-Chain Fatty Acids (Other)
Placebo
Colon-delivery capsules of microcrystalline cellulose
干预措施: Placebo (Other)
结局指标
主要结局
HDAC expression
时间窗: 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
时间窗: 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
次要结局
- Cytokine levels(Throughout study completion, on average 2 years)
- Salivary cortisol response to stress(Throughout study completion, on average 2 years)
- C-reactive protein levels(Throughout study completion, on average 2 years)
- Brain metabolite concentration(Throughout study completion, on average 2 years)
- Serum short-chain fatty acid levels(Throughout study completion, on average 2 years)
- Heart rate variability(Throughout study completion, on average 2 years)
- Blood pressure(Throughout study completion, on average 2 years)
- Heartbeat(Throughout study completion, on average 2 years)
- Self-reported stress(Throughout study completion, on average 2 years)
研究者
Lukas Van Oudenhove
MD, PhD
Universitaire Ziekenhuizen KU Leuven