The Role of Short-chain Fatty Acids (SCFAs) in Regulating Stress Responses, Eating Behavior, and Nutritional State in Anorexia Nervosa: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- KU Leuven
- 入组人数
- 92
- 试验地点
- 2
- 主要终点
- Salivary cortisol response following TSST
研究概览
简要总结
This clinical trial aims to test the psychobiological effects of certain substances produced by gut bacteria, known as short-chain fatty acids (SCFAs), in people with anorexia nervosa.
详细描述
Objective This protocol proposes investigating the effects of short-chain fatty acids (SCFAs), produced by gut bacterial fermentation of dietary fiber, as mediators of microbiota-gut-brain interactions on the acute stress response, eating behavior, and nutritional state in malnourished patients with anorexia nervosa (AN). SCFAs have recently been proposed as crucial mediators of the microbiome's effects on the host. Emerging evidence suggests that SCFAs impact human physiology through various physiological pathways and may regulate stress responses and eating behavior.
Method The investigators will conduct a randomized, triple-blind, placebo-controlled trial in 92 AN patients. Patients will receive either a placebo or a mixture of SCFAs (acetate propionate, butyrate) using colon-delivery capsules (CDCs) for six weeks. This clinical trial is an add-on to the standard inpatient psychotherapeutic program focusing on nutritional rehabilitation.
Hypotheses The investigators hypothesize that colonic SCFAs delivery will modulate neuroendocrine, cardiovascular, and subjective responses to an acute laboratory psychosocial stress task. As secondary outcome measures, the investigators will assess alterations in restrictive eating behavior and nutritional status, as reflected by changes in body mass index (BMI). Additionally, the investigators will explore changes in microbiota composition, gastrointestinal symptoms, eating disorder psychopathology, and related comorbidities.
Discussion The findings of this study can enhance our understanding of how gut microbiota-produced metabolites, particularly SCFAs, impact the stress response and eating behavior of individuals with AN. It has the potential to provide essential insights into the complex interplay between the gut, stress system, and eating behavior and facilitate new therapeutic targets for stress-related psychiatric disorders.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants are female.
- •Participants are at least 16 years of age.
- •Participants are Dutch-speaking.
- •Participants meet the diagnostic criteria of anorexia nervosa based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). The first time the participant met these criteria was less than seven years ago.
- •Participants have a current BMI < 17,5 (kg/m2).
- •Participants are on the waiting list for a psychiatric/psychotherapeutic inpatient treatment program with nutritional rehabilitation on the eating disorder ward of the University Psychiatric Hospital Leuven.
- •Participants can access a -18°C home freezer for stool storage.
排除标准
- •Any medical or psychiatric disorder, which in the Investigator's opinion, might jeopardize the participant's safety or compliance with the protocol.
- •Any prior or concomitant treatment(s) that might jeopardize the participant's safety or that would compromise the integrity of the Trial.
- •Substance/alcohol/illegal drug abuse or dependence or evidence for chronic uses of sedatives, drugs and/or sleep medication.
- •High caffeine intake (> 1000 ml coffee daily or equivalent quantities of other caffeine-containing substances).
- •Use of pre- or probiotics within the last month before the start of the study.
- •Use of antibiotics within the last three months before the start of the study.
- •Pregnancy or intention to become pregnant.
- •Previous experience with one of the tasks used in the study.
- •Use of antipsychotics
- •Use of selective serotonin reuptake inhibitors (SSRIs), oral contraceptives, or other drugs is allowed if patients are on a stable dosage for at least four weeks.
结局指标
主要结局
Salivary cortisol response following TSST
时间窗: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
Changes in salivary cortisol levels in response to acute laboratory stress (Trier Social Stress Test).
Restrictive food choices during Food Choice Task
时间窗: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention)
Food choices made under stress are measured through the food choice task, focusing on the proportion of high-fat food items chosen over the reference item.
Nutritional status (BMI)
时间窗: Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following the start of the intervention)
Nutritional status of participants determined by calculating Body Mass Index (BMI) from recurrently measured weight
次要结局
- Neuroendocrine Measures (ACTH)(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Subjective stress in relation to TSST(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Subjective stress appraisal in relation to TSST(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Electrodermal activity to acute laboratory stress(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Eating Disorder Symptoms(Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following)
- Restrained, emotional and external eating behaviour(Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following)
- Neuroendocrine Measures (salivary alpha amylase)(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Subjective anxiety in relation to TSST(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Subjective hunger in relation to TSST(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Subjective appetite in relation to TSST(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Hedonic hunger(Self-reported questionnaires are completed at the baseline visit (at hospital admission and before intervention), three weeks into the intervention, post intervention (following six weeks of intervention) and at the follow-up visit (12 weeks following)
- Heart rate response to acute laboratory stress(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Heart rate variability to acute laboratory stress(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))
- Self controlled choices during Food Choice Task(Baseline (at hospital admission and before intervention) and post-intervention (following six weeks of intervention))