Clinical trial NCT06823557: Investigation of the Mechanisms of the Gut-brain Axis in Binge Eating and Obesity.
Official title: Gut2Brain: Investigation of the Mechanisms of the Gut-brain Axis in Binge Eating and Obesity
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Binge Eating Disorder
Obesity
Keywords: psychobiotic treatment
Study of neuro-psycho-biological mechanisms
Microbiota-Gut-Brain Axis (MGBA)
Obesity
Binge eating disorder
Lead sponsor: Universidade do Porto
Sponsor class: OTHER
Collaborators: name: University of Minho
name: Braga Hospital
First posted: 2025-02-12
Enrollment: 104
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This randomized controlled trial (RCT) will compare three groups: a BED+obesity group, an obesity group (without BED), and a normal-weight group (without BED). Participants will be randomized and allocated into two arms in a double-blind, placebo-controlled design: an intervention group receiving a psychobiotic and a control group receiving a placebo matched in taste and appearance. Randomization will follow the CONSORT guidelines, utilizing a computer-generated sequence of random numbers in a 1:1 ratio. Groups will be matched based on BMI, age, and sex.

Participants meeting the inclusion and exclusion criteria will undergo a semi-structured clinical interview to diagnose BED. They will also receive detailed information about the study and sign an informed consent form prior to participation. Assessments will take place at two time points: baseline (T0), before initiating the psychobiotic or placebo, and follow-up (T1), after completion of the assessment protocol.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Gut Microbiota outcomes - Gut-Bacteria Composition
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Gut Microbiota outcomes - Molecules released by the gut-bacteria
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Psycho-behavioral outcomes - Three Factor Eating Questionnaire-21
timeFrame: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
measure: Psycho-behavioral outcomes - Eating Expectancy Inventory
timeFrame: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
measure: Psycho-behavioral outcomes - Negative urgency subscale
timeFrame: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
measure: Psycho-behavioral outcomes - Difficulties in Emotion Regulation Scale
timeFrame: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
measure: Psycho-behavioral outcomes - Distress Tolerance Scale
timeFrame: Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.
measure: Neurofunctioning outcomes - Default mode network
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Neurofunctioning outcomes - Salience network
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Neurofunctioning outcomes - Meso/Paralimbic network
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Neurofunctioning outcomes - Executive network
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Ghrelin
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Glucagon-Like Peptide 1
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Peptide YY
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Leptin
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Insulin
timeFrame: Change measures: baseline and end of treatment at 12 weeks
measure: Appetitive hormones outcomes - Cortisol
timeFrame: Change measures: baseline and end of treatment at 12 weeks
Secondary outcomes:
measure: Eating Disorder Examination
timeFrame: baseline moment
Other outcomes:
Locations:
city: Porto
country: Portugal
facility: Center for Psychology at University of Porto
state: Paranhos
Study officials:
affiliation: Center for Psychology at University of Porto (CPUP)
name: Eva M. Conceição
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Engineering Biological (CEB) at University of Minho
name: Clarisse N. Salomé
role: PRINCIPAL_INVESTIGATOR
References: