Investigation of the Mechanisms of the Gut-brain Axis in Binge Eating and Obesity.

Phase 1

Not yet recruiting

• Conditions: Binge Eating Disorder; Obesity

• Registration Number: NCT06823557
• Lead Sponsor: Universidade do Porto

Brief Summary

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.

Detailed Description

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.

Between the second and third blood samples collected, participants will respond with some self-report measures. Specifically, self-report measures will assess socio-demographic data (age, sex, gender, education levels, marital status, and weight history) and psychological aspects: 1) emotional regulation and impulse control, distress tolerance, and positive and negative affects; 2) eating behavior, assessing eating expectancy, emotional eating, compulsive eating, and restraint eating. Then participants will do resting-state functional magnetic resonance imaging (rs-FMRI) performed to evaluate resting-state network connectivity.

Stool samples will be collected using a kit that includes all the necessary tools for proper sample collection and preparation for microbiota analysis.

The psychobiotic and the placebo package and instructions will be delivered during this scheduled appointment in Braga Hospital. All participants will be contacted weekly during the 12-week trial to ensure/increase adherence to the guidelines of prebiotic/placebo intervention.

Statistical Analyses:

Overall, multivariate analysis of variance (MANOVA) and/or general linear models (GLM) with mixed-model repeated measures will be used to examine group differences related to MGBA mechanisms, as well as significant main effects and interaction effects between baseline (T0) and the end of the RCT (T1). Structural equation modeling (SEM) will be employed to evaluate MGBA mechanisms as mediators of the changes observed between T0 and T1.

Study Timeline

• Study First Submitted: 2025-01-17
• Study First Submitted QC: 2025-02-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-28
• Study Start: 2025-04
• Primary Completion: 2028-09
• Study Completion: 2030-03

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Gut Microbiota outcomes - Gut-Bacteria Composition	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	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	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	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	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	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	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	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.
Psycho-behavioral outcomes - Distress Tolerance Scale	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
Neurofunctioning outcomes - Default mode network	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	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	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	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	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	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	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	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.

Secondary Outcome Measures

Name	Time	Method
Eating Disorder Examination	baseline moment	Eating Disorder Examination (EDE): semi-structured clinical interview for the diagnosis of binge eating disorder

Trial Locations

Locations (1)

Center for Psychology at University of Porto; 🇵🇹 Porto, Paranhos, Portugal