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

Официальное название

A Prospective Clinical Study to Investigate Dopamine Level Changes in the Brain at Food Cognition by GLP-1 Receptor Agonists

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Semaglutide
  Participants receive an 8-week subcutaneous semaglutide dose-escalation treatment using Wegovy: 0.25 mg once weekly for the first 4 weeks, followed by 0.5 mg once weekly for the next 4 weeks.

Первичные конечные точки

• Change in Dopamine Binding Potential During the Look, Smell, and Drink Period [Срок оценки: 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.]

Вторичные конечные точки (4)

• Change in Dopamine Binding Potential During the Post-Ingestive Period [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

South Korea · 1 центр

• Seoul National University Hospital — Seoul

Идентификаторы

NCT: NCT07732426 · 2501-006-1602

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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