Effects of Semaglutide on Brain Dopamine Responses to Food Cues in Adults With Obesity and Food Addiction Tendencies

Seoul National University Hospital30 enrolled

Overview

The goal of this clinical trial is to investigate how semaglutide affects the way the brain responds to food in adults with obesity and food addiction tendencies. The main goals of this study are: * To see if semaglutide changes dopamine-related activity in the brain during the look, smell, and drink period. * To see if semaglutide changes dopamine-related brain signals during the post-ingestive period. * To see if semaglutide changes psychological survey results and cognitive task results. Adults with obesity and food addiction tendencies will join this study. Each participant will receive semaglutide treatment for 8 weeks. Each participant will have two brain scans using \[11C\]raclopride PET. During each PET scan, participants will: * View food images. * Receive chocolate milk through a tube while lying in the scanner. * Use a tablet during the scan to rate their hunger, desire for the chocolate milk drink, and liking of the drink.

1. Background and Rationale GLP-1 receptor agonists, including semaglutide, are effective treatments for obesity. However, the brain mechanisms underlying their effects on appetite, food reward, and eating behavior remain incompletely understood. Food-related visual and olfactory cues may engage dopamine-mediated reward pathways during the pre-ingestive phase, and post-ingestive signals may further influence dopamine signaling after food intake. This study will use \[11C\]raclopride positron emission tomography (PET) to assess dopamine-related binding measures in the human brain. The study will examine whether semaglutide changes dopamine-related brain responses during food cue and drink exposure and during the post-ingestive period. 2. Study Protocol and Procedures This is a prospective clinical trial using a 2-by-2 crossover design. Participants will receive once-weekly semaglutide treatment for 8 weeks and will undergo two \[11C\]raclopride PET scans. The scans will be performed under conditions with and without the effect of semaglutide, depending on group assignment. Before each PET imaging session, participants will complete baseline assessments, including body measurements, psychological surveys, and computer-based cognitive tasks. \[11C\]raclopride will then be administered according to the PET protocol. Participants will undergo brain PET imaging while lying in the scanner. During the imaging session, participants will complete a standardized chocolate milk drink task. This task includes a baseline period, exposure to chocolate milk images, smelling the chocolate milk drink, and the post-ingestive stage using the chocolate milk drink delivered through a tube. During the scan, participants will use a tablet to rate hunger, desire for the chocolate milk drink, and liking of the drink at set time points. The same PET task procedures will be used across study conditions. This will allow researchers to compare dopamine-related PET measures, psychological survey results, and cognitive task results between conditions with and without the effect of semaglutide.

Eligibility

Sex: ALLMin age: 19 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants aged between 19 and 50 years. * Eligible for treatment with semaglutide, defined as either: * Initial body mass index (BMI) of 30 kg/m2 or higher; or * Initial BMI of 27 kg/m2 to less than 30 kg/m2 with at least one weight-related comorbidity, such as dysglycemia, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. * Mild or greater food addiction tendency, defined as a Yale Food Addiction Scale (YFAS) score of 3 or higher. * Able to understand the study tasks and provide appropriate responses. Exclusion Criteria: * Use of medications that may affect body weight or dopaminergic medications within the past 2 months. * Known hypersensitivity to semaglutide. * Pregnant, breastfeeding, or planning to become pregnant. * Severe renal impairment, hepatic impairment, heart failure, acute pancreatitis, or thyroid disease. * Any medical condition, disease, or medical history that, in the investigator's judgment, would make it difficult for the participant to complete the study or would interfere with interpretation of the study results. * Allergy to ingredients in chocolate milk, including milk or soy, or to ingredients that may be present through cross-contamination, including egg, buckwheat, peanut, wheat, peach, tomato, walnut, pork, or beef. * Participants with both no self-reported preference for chocolate milk and a chocolate milk preference score of less than 5 on a 10-point visual analog scale (VAS).

Outcomes

Primary Outcomes

Change in Dopamine Binding Potential During the Look, Smell, and Drink Period

Dopamine D2/D3 receptor binding potential is measured using \[11C\]raclopride PET during the food cue and drink period. The outcome is the within-participant difference in binding potential between the on-drug and off-drug/post-washout conditions.

Time frame: Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation.

Secondary Outcomes

Change in Dopamine Binding Potential During the Post-Ingestive Period

Dopamine D2/D3 receptor binding potential is measured using \[11C\]raclopride PET during the post-ingestive period after the drink. The outcome is the within-participant difference in binding potential between the on-drug and off-drug/post-washout conditions.

Time frame: Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation.

State Food Craving Score

State food craving is assessed using the General Food Cravings Questionnaire-State (G-FCQ-S). Each of the 15 items is evaluated on a 0 to 100 scale, where higher scores indicate greater intensity of the felt state.

Time frame: Immediately before and after PET imaging. Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation.

Chocolate Milk Liking, Chocolate Milk Wanting, and Fullness Ratings (VAS-100)

Liking and wanting for the chocolate milk stimulus, as well as general fullness, are assessed repeatedly during PET imaging using 0-to-100 visual analogue scale ratings. For liking and wanting, higher scores indicate greater liking of or desire for the chocolate milk stimulus. For fullness, higher scores indicate greater subjective fullness. Ratings are collected at 15 predefined time points during each PET scan.

Time frame: During each 92-minute PET scan, at 10, 20, 30, 40, 50, 51, 54, 57, 60, 65, 70, 75, 80, 85, and 90 minutes.

Food-Specific Attentional Bias

Food-specific attentional bias is assessed using a computer-based dot-probe task with webcam-based eye tracking. Bias is calculated from reaction time differences between probes replacing food versus neutral images, and from gaze-based measures including dwell time toward food versus neutral images and first saccade direction. Higher values indicate greater attentional bias toward food stimuli.

Time frame: Before PET imaging. Group A: At Baseline (Day 0) and 8 weeks (±3 days) after starting semaglutide. Group B: At 8 weeks (±3 days) after starting semaglutide and 8 weeks after semaglutide discontinuation.

Effects of Semaglutide on Brain Dopamine Responses to Food Cues in Adults With Obesity and Food Addiction Tendencies

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts