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

NCT06823557 | Not Yet Recruiting Phase 1

• 1 other identifier: UPorto_Gut2Brain
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

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.

Conditions

Binge Eating Disorder; Obesity

Keywords

psychobiotic treatment; Study of neuro-psycho-biological mechanisms; Microbiota-Gut-Brain Axis (MGBA); Obesity; Binge eating disorder

Outcome Measures

Primary Outcomes (17)

• Gut Microbiota outcomes - Gut-Bacteria Composition

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Gut Microbiota outcomes - Molecules released by the gut-bacteria

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Psycho-behavioral outcomes - Three Factor Eating Questionnaire-21

  Three Factor Eating Questionnaire-21 (TFEQ-21): assesses psychopathology and behaviors related to eating disorders, generating 3 subscales: emotional eating; compulsive eating; restraint eating.

  Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.

• Psycho-behavioral outcomes - Eating Expectancy Inventory

  \- The Eating Expectancy Inventory (EEI): evaluates cognitive expectations regarding eating

  Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.

• Psycho-behavioral outcomes - Negative urgency subscale

  Negative urgency subscale from the Urgency, Premeditation, Perseverance, and Sensation Seeking scales (UPPS): assesses the tendency to act rashly/impulsively when experiencing negative emotions.

  Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.

• Psycho-behavioral outcomes - Difficulties in Emotion Regulation Scale

  Difficulties in Emotion Regulation Scale (DERS): self-report measure developed to assess difficulties in emotional dysregulation.

  Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.

• Psycho-behavioral outcomes - Distress Tolerance Scale

  The Distress Tolerance Scale (DTS): scale that assesses ability to experience, tolerate, and function in a context of emotional distress

  Change measures: baseline, end of treatment at 12 weeks and follow-up at 12 weeks post-treatment.

• Neurofunctioning outcomes - Default mode network

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Neurofunctioning outcomes - Salience network

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Neurofunctioning outcomes - Meso/Paralimbic network

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Neurofunctioning outcomes - Executive network

  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

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Ghrelin

  Assessment of appetitive hormones that modulate eating behavior: * Ghrelin is an orexigenic hormone with stimulatory effects on appetite and food intake.

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Glucagon-Like Peptide 1

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Peptide YY

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Leptin

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Insulin

  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.

  Change measures: baseline and end of treatment at 12 weeks

• Appetitive hormones outcomes - Cortisol

  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

  Change measures: baseline and end of treatment at 12 weeks

Secondary Outcomes (1)

• Eating Disorder Examination

  baseline moment

Study Arms (2)

Psychobiotic group

EXPERIMENTAL

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.

Dietary Supplement: Psychobiotic treatment

Control group

PLACEBO COMPARATOR

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.

Other: Placebo treatment

Interventions

Psychobiotic treatment DIETARY_SUPPLEMENT

The dietary supplementation will follow established guidelines, recommending an intake of 16 g of prebiotic per day, distributed across three meals, for a duration of 12 weeks.

Also known as: Prebiotic, Inulin

Psychobiotic group

Placebo treatment OTHER

The control group will receive identical packaging that matches the experimental treatment in taste and appearance and will follow the same guidelines for consuming the placebo. For ethical reasons, after the end of the RCT, the control group will be given the option to receive the same prebiotic supplement.

Also known as: Maltodextrin (Placebo)

Control group

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidade do Porto: lead
• University of Minho: collaborator
• Braga Hospital: collaborator

Study Sites (1)

Center for Psychology at University of Porto

Porto, Paranhos, 4200-135, Portugal

Location

MeSH Terms

Conditions

Binge-Eating Disorder; Obesity

Interventions

Prebiotics; Inulin; maltodextrin

Condition Hierarchy (Ancestors)

Feeding and Eating Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Dietary Supplements; Food and Beverages; Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Fructans

Study Officials

• Eva M. Conceição

  Center for Psychology at University of Porto (CPUP)

  PRINCIPAL INVESTIGATOR

• Clarisse N. Salomé

  Center for Engineering Biological (CEB) at University of Minho

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva M. Conceição

CONTACT

+351 917 853 236; econceicao@fpce.up.pt

Catarina C. Gomes

CONTACT

914841706; 202408503@fpce.up.pt

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Fellow

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: February 12, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: from jan 2030 to jan 2035
• Access Criteria: Researcher with research track record in the filed by contacting the PI of the study.

Locations

PT (1)