Gut2Brain: Investigation of the Mechanisms of the Gut-brain Axis in Binge Eating and Obesity
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Psycho-behavioral outcomes - Distress Tolerance Scale
研究概览
简要总结
Binge Eating Disorder (BED) is a recently recognized eating disorder, characterized by recurrent episodes of overeating with a loss of control. Highly comorbid with obesity, BED is associated with poor outcomes in weight loss treatments and presents unique challenges due to its distinct neuro-psycho-biological mechanisms, which remain poorly understood. The Microbiota-Gut-Brain Axis (MGBA) is a bidirectional communication system linking the gut microbiota with the central nervous system, that plays a critical role in regulating appetite, mood, and eating behavior. Dysregulations in MGBA may contribute to the development and maintenance of BED, offering a novel framework for understanding its complex mechanisms and identifying new therapeutic targets. Psychobiotics -pre-, pro-, or symbiotics that modulate the microbiota- emerge as a promising treatment strategy to address BED symptoms by influencing MGBA activity.
The goal of this randomized clinical trial (RCT) is to investigate the role of psychobiotics in modulating the gut-brain axis and improving binge eating in adults, with a particular focus on evaluating these effects independently of obesity status. This project stands out for its comprehensive approach to understanding BED, integrating psychological, neurofunctional, hormonal, and microbiota factors that contribute to this complex disorder.
The main questions it aims to answer are:
- What specific alterations in the MGBA pathways are associated with BED?
- Can psychobiotic supplementation effectively reverse microbiota alterations and modulate MGBA activity, ultimately improving BED symptoms? Researchers will compare participants receiving psychobiotics to those receiving a look-alike substance that contains no drug (a placebo) to evaluate whether psychobiotics impact endocrine hormones, neurofunction, psychological and behavioral factors related to eating regulation, and BED symptoms.
Participants will:
- Undergo an assessment protocol that includes microbiota sampling, blood tests for hormone analysis, neurofunctional evaluations, and psychological/behavioral assessments before and after the psychobiotics/ placebo intervention.
- Take psychobiotics or a placebo daily for 12 weeks and receive well-being monitoring
- Participate in follow-up visits three months after the intervention to monitor changes in BED symptoms and related parameters.
详细描述
This research project aims to investigate the role of psychobiotics in reversing MGBA alterations specific to BED. Therefore, a two-arm Randomized Clinical Trial (RCT) will be conducted. Participants will include individuals with BED and obesity, individuals with obesity only, and individuals with normal weight that will be randomly assigned to one of two groups:
i) an intervention group receiving psychobiotic supplementation ii) a control group receiving placebo supplementation. The sample size was computed considering the sample needed for 3 groups comparison in the RCT. G Power was used for (Mixed) ANOVAs considering f = 0.25, power = 90%, α = 0.05, and corr = 0.5., and 15% dropout.
At both the beginning and end of the trial, participants will undergo an assessment protocol.
Assessment protocol:
Participants will be invited to visit Braga Hospital where the assessment will take place for a scheduled appointment to undergo the assessment protocol for approximately 2 hours. The first step will involve the assessment of appetitive hormones through blood samples collected at three time points. The first blood sample (0 minutes) will be taken after a 12-hour overnight fast. Participants will consume 600 mL of a standardized liquid test meal, and additional blood draws will occur 10 and 30 minutes after the meal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Portuguese adults (25 with normal weight; 25 with obesity only (30 ≤ BMI < 40) and BED; 54 with BED)
- •Residents in Portugal for the past 10 years
排除标准
- •Significant weight loss (>5% of body weight) in the past 2 years
- •Antibiotic use in the past 6 months
- •History of surgery or medical/psychiatric diseases
- •Pregnant or breastfeeding
- •History of drug use or dependence
- •Use of medications that impact weight
- •Have metal implants or pacemakers
研究组 & 干预措施
Psychobiotic group
An intervention group receiving a psychobiotic-a native inulin prebiotic. Native inulin extracted from chicory roots was selected as the psychobiotic since it is a mixture of short inulin molecules, which are metabolized primarily in the proximal colon and are more rapidly fermented, with longer chain ones, which are fermented later and slower in the distal colon. The psychobiotic nature of Inulin has been suggested in recent literature.
干预措施: Psychobiotic treatment (Dietary Supplement)
Control group
A control group receiving a taste/appearance-matched placebo- the maltodextrin. Maltodextrin is a carbohydrate consisting of short chains of glucose molecules. It is commonly used as a placebo in clinical trials, providing no significant health benefits or harm when consumed with moderation.
干预措施: Placebo treatment (Other)
结局指标
主要结局
Psycho-behavioral outcomes - Distress Tolerance Scale
时间窗: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
The Distress Tolerance Scale (DTS): scale that assesses ability to experience, tolerate, and function in a context of emotional distress
Gut Microbiota outcomes - Gut-Bacteria Composition
时间窗: Change measures: baseline and end of treatment at 12 weeks
Stool samples from each participant will be fermented by the prebiotic to allow direct comparison of individual alterations in vitro and in vivo of the microbiome. Changes in gut-bacteria composition and its adhesion into the mucus layer will be analyzed.
Psycho-behavioral outcomes - Eating Expectancy Inventory
时间窗: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
- The Eating Expectancy Inventory (EEI): evaluates cognitive expectations regarding eating
Appetitive hormones outcomes - Cortisol
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: - Cortisol is responsible for the stress response, acting on the hypothalamic-pituitary axis, and it is associated with increased eating
Gut Microbiota outcomes - Molecules released by the gut-bacteria
时间窗: Change measures: baseline and end of treatment at 12 weeks
Stool samples from each participant will be fermented by the prebiotic to allow direct comparison of individual alterations in vitro and in vivo of the microbiome. Molecules released by the bacteria, including short-chain fatty acids (SCFA), lipopolysaccharides (LPS), gamma-aminobutyric acid (GABA), dopamine, and serotonin, which modify host metabolism and central regulation of appetite directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms, will be traced during fermentations.
Appetitive hormones outcomes - Ghrelin
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: * Ghrelin is an orexigenic hormone with stimulatory effects on appetite and food intake.
Psycho-behavioral outcomes - Three Factor Eating Questionnaire-21
时间窗: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
Three Factor Eating Questionnaire-21 (TFEQ-21): assesses psychopathology and behaviors related to eating disorders, generating 3 subscales: emotional eating; compulsive eating; restraint eating.
Psycho-behavioral outcomes - Negative urgency subscale
时间窗: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
Negative urgency subscale from the Urgency, Premeditation, Perseverance, and Sensation Seeking scales (UPPS): assesses the tendency to act rashly/impulsively when experiencing negative emotions.
Psycho-behavioral outcomes - Difficulties in Emotion Regulation Scale
时间窗: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
Difficulties in Emotion Regulation Scale (DERS): self-report measure developed to assess difficulties in emotional dysregulation.
Neurofunctioning outcomes - Default mode network
时间窗: Change measures: baseline and end of treatment at 12 weeks
Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The DMN is involved in self-referential processing, which includes monitoring the external environment as well as physical and emotional states.
Neurofunctioning outcomes - Salience network
时间窗: Change measures: baseline and end of treatment at 12 weeks
Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The DMN is involved in self-referential processing, which includes monitoring the external environment as well as physical and emotional states. The SN is involved in detecting the salience of stimuli, integrating emotional arousal, food, and reward processing.
Neurofunctioning outcomes - Meso/Paralimbic network
时间窗: Change measures: baseline and end of treatment at 12 weeks
Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The MPN is involved in processing emotional information and interoceptive awareness.
Appetitive hormones outcomes - Peptide YY
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: - Peptide YY (PYY) have an anorexigenic effect and are thought to contribute to impaired satiation and binge eating tendencies.
Appetitive hormones outcomes - Leptin
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: * Leptin acts as a regulatory signal reflecting the adipose tissue stores. Both insufficiency and resistance to its actions promote hunger and increased food intake. Leptin can decrease food reward and act in the central nervous system as regulators of energy homeostasis.
Neurofunctioning outcomes - Executive network
时间窗: Change measures: baseline and end of treatment at 12 weeks
Neurofunctioning will be assessed through rs-fMRI. Specifically, we aim to compare the resting-state networks (RSNs), such as the default mode network (DMN), the salience network (SN), the meso/paralimbic network (MPN), and the executive network (EN) across the three groups. The EN is involved in cognitive control and inhibitory processes, such as the termination of food consumption
Appetitive hormones outcomes - Glucagon-Like Peptide 1
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: * Glucagon-Like Peptide 1 (GLP-1) have an anorexigenic effect and are thought to contribute to impaired satiation and binge eating tendencies. GLP-1 has been the target of novel therapeutics for weight loss, but few studies have examined its impact on BED.
Appetitive hormones outcomes - Insulin
时间窗: Change measures: baseline and end of treatment at 12 weeks
Assessment of appetitive hormones that modulate eating behavior: Insulin can decrease food reward and act in the central nervous system as regulators of energy homeostasis.
次要结局
- Eating Disorder Examination(baseline moment)
研究者
Eva Conceição
Research Fellow
Universidade do Porto