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
- 2
- 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")
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
- 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)
- Cytokine levels(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