Brain Dopamine Dynamics in Obesity (BDDO)
This study measures the brain's dopamine response to milkshake consumption in people with a healthy weight and people with obesity and examines whether this response differs between the two groups. Dopamine release will be measured using ultra-high-resolution positron emission tomography (PET) imaging with the NeuroEXPLORER scanner. The study will also examine how the dopamine response relates to hormonal responses measured at the same time and to participants' food intake behavior.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This study aims to address three key questions: (1) whether the two phases of dopamine release in the striatum, a brain region involved in reward and motivation, during and after milkshake consumption differ between people with a healthy weight and people with obesity, and between men and women; (2) how metabolic and hormonal responses relate to dopamine release; and (3) whether dopamine-related networks outside the striatum differ between weight groups and predict eating behavior. These findings may improve our understanding of overeating and obesity and help inform the development of treatments that target the brain's dopamine system.
Each participant will complete four visits:
- Informed consent and screening to determine eligibility.
- A practice session to become familiar with PET scanning and the device used to deliver the milkshake.
- An MRI scan and assessments of eating behavior.
- A PET scan to measure dopamine release before and during milkshake delivery, with blood samples collected before and during the scan and questionnaires and tasks completed before and after the scan.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 1
Contactos e Locais
Contato de estudo
- Nome: Elizabeth Sanchez Rangel, MD
- Número de telefone: 203-785-6430
- E-mail: elizabeth.sanchezrangel@yale.edu
Estude backup de contato
- Nome: Mireille Serlie, MD PhD
- Número de telefone: 2037375538
- E-mail: mireille.serlie@yale.edu
Locais de estudo
-
-
Connecticut
-
New Haven, Connecticut, Estados Unidos, 06520
- Yale School of Medicine
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- BMI 20-25 kg/m² (normal weight group) or BMI 30-45 kg/m² (obesity group)
- Stable body weight in the 3 months prior to enrollment (<5%weight change)
- Male sex or postmenopausal female (defined as cessation of menstrual periods for ≥12 consecutive months or FSH >25.8 mIU/mL)
- Able to read, write, and speak English
- Capable of giving informed consent
Exclusion Criteria:
- Premenopausal status in women
- Smoking (current use of any tobacco or nicotine products)
- History of or current psychiatric disorder
- History of or current neurological disorder
- History of bleeding disorder or use of anticoagulants
- History of or current eating disorder (Eating Disorder Examination Questionnaire)
- Presence of type 1 or type 2 diabetes mellitus
- Elevated liver enzymes (>2× the upper limit of normal)
- Renal insufficiency (eGFR <15 mL/min/1.73m²)
- Anemia and/or Hematocrit <35 vol%
- Uncontrolled thyroid disease
- Lactose intolerance
- Current use of systemic hormone therapy, including oral, transdermal, or injectable estrogen or combined estrogen-progestogen preparations
- Radiation exposure for research purposes within the past year such that participation in this study would place them over guideline limits for annual radiation exposure (an effective dose of 5 rem received per year).
- Current, past or anticipated exposure to radiation in the workplace within one year
- Presence of any somatic disorder or medication use that interferes with brain functional networks or metabolic response to food
- Shift work
- Current use of cannabis (any form), cocaine, amphetamines, or other recreational substances with known dopaminergic effects
- Heavy alcohol use, defined as >15 standard drinks per week for men or >8 standard drinks per week for women (National Institute on Alcohol Abuse and Alcoholism thresholds)
- Contraindications for MRI: metal implants incompatible with MRI, claustrophobia, large colored tattoos, or body weight >285 pounds
- Pacemaker in situ or other implanted electronic device
- Childhood-onset obesity (onset before age 10 years)
- Current or past (within last year prior to enrollment) pharmacological obesity treatment
- Past surgical obesity treatment (bariatric surgery)
- Current use of structured meal replacement programs
- Blood donation within 8 weeks prior to study
- Active oral or perioral conditions that may alter taste perception or compromise safety during gustometer use
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Adults with obesity
Four visits per participant: screening, PET practice session, MRI+behavioral assessment, milkshake+PET scan. |
Strawberry, banana, chocolate, or vanilla flavored, delivered through a gustometer during the practice session and PET scan. A next-generation ultra-high-performance dedicated human brain PET scanner.
Outros nomes:
Carbon-11 radiolabeled PET ligand with high affinity and selectivity for postsynaptic dopamine receptors; one of the standard radiotracers for measuring dopamine release in humans.
Outros nomes:
|
|
Experimental: Adults with normal weight
Four visits per participant: screening, PET practice session, MRI+behavioral assessment, milkshake+PET scan. |
Strawberry, banana, chocolate, or vanilla flavored, delivered through a gustometer during the practice session and PET scan. A next-generation ultra-high-performance dedicated human brain PET scanner.
Outros nomes:
Carbon-11 radiolabeled PET ligand with high affinity and selectivity for postsynaptic dopamine receptors; one of the standard radiotracers for measuring dopamine release in humans.
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Dopamine (DA) release
Prazo: Visit 4, approximately week 4. Baseline D2/3R binding potential will be assessed at T=30'. PET time-activity curves are then measured continuously for 60 minutes from milkshake onset.
|
Orosensory and post-ingestive DA release in the ventral and dorsal striatum during and after milkshake consumption |
Visit 4, approximately week 4. Baseline D2/3R binding potential will be assessed at T=30'. PET time-activity curves are then measured continuously for 60 minutes from milkshake onset.
|
|
Time to onset of DA peaks
Prazo: Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Time to onset of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Duration of DA peaks
Prazo: Visit 4, approximately week 4.PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Duration of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4.PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Time to onset of DA peaks between men and women
Prazo: Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Time to onset of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Duration of DA peaks between men and women
Prazo: Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Duration of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
|
Magnitude of DA release between men and women
Prazo: Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Magnitude of orosensory and post-ingestive DA peaks in the ventral and dorsal striatum |
Visit 4, approximately week 4. PET time-activity curves are measured continuously for 60 minutes from milkshake onset (30-90 minutes after initiation of radiotracer administration).
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Glucose
Prazo: Glucose will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Glucose will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
|
Insulin
Prazo: Insulin will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Insulin will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
|
FFA
Prazo: FFA will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
FFA will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset at Visit 4, approximately week 4.
|
|
Gut peptides (tbd)
Prazo: Gut peptides will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset.
|
To assess the relationship between the metabolic response to the milkshake and striatal dopamine release, we will use a machine learning approach including network analysis. |
Gut peptides will be collected after an overnight fast on the morning of the PET scan and at 7.5, 15, 30, and 45 minutes after milkshake onset.
|
|
Yale Food Addiction Scale 2.0 score
Prazo: After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
Total score ranges from 0 to 11. Higher symptom counts indicate more symptoms of addictive-like eating. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
|
Barratt Impulsiveness Scale (BIS-11) score
Prazo: After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
A 30-item self-report questionnaire designed to measure human impulsiveness as a multidimensional personality and behavioral trait. Total score range 30 to 120, with higher scores reflecting greater impulsiveness. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
|
Dietary Fat and Free Sugar - Short Questionnaire (DFS)
Prazo: After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
A 26-item self-report tool to measure how often a person eats foods high in saturated fat and free sugar over the past 12 months. Total score range 26 to 130, with higher scores reflecting more frequent consumption of foods high in saturated fat and/or free sugars. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
|
Change in Delay Discounting Task
Prazo: The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=105' (duration of the task is 10 minutes)
|
A behavioral assessment (computer task) to determine reward sensitivity (how much a person devalues a reward as the wait time for it increases). Calculated as Discount rate (k). Higher k indicates greater preference for immediate rewards. |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=105' (duration of the task is 10 minutes)
|
|
Change in Iowa Gambling Task score
Prazo: The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=115' (duration of the task is 15 minutes)
|
The Iowa Gambling Task is a behavioral task that assesses decision-making under uncertainty by asking participants to select cards from four decks with different rewards and losses. The net score is calculated by subtracting the number of selections from disadvantageous decks from the number of selections from advantageous decks. |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=115' (duration of the task is 15 minutes)
|
|
Behavioral Inhibition System/Behavioral Activation System Scale score
Prazo: After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
The Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) Scales assess sensitivity to punishment and reward. The questionnaire contains 24 items, including 20 scored items and 4 filler items. It yields four subscale scores: Behavioral Inhibition (7-28), BAS Drive (4-16), BAS Fun Seeking (4-16), and BAS Reward Responsiveness (5-20). Higher scores indicate greater sensitivity to punishment, stronger pursuit of goals, greater fun seeking, and greater responsiveness to reward, respectively. |
After screening (visit 1), the PET test session (visit 2), the questionnaire will be administered during visit 3 (duration 10 minutes); after completion of the MRI
|
|
Change in Visual Analogue Scale (VAS) score
Prazo: The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=100' (duration of the task is 2 minutes)
|
VAS to assess hunger and satiety on a scale of 0-100. Higher hunger scores indicate greater hunger, while higher satiety/fullness scores indicate greater satiety/fullness |
The task will be administered at the PET Center after an overnight fast at baseline (before radio tracer administration) and after the PET scan at T=100' (duration of the task is 2 minutes)
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Mireille Serlie, MD PhD, Yale University
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 2000042630
- 1R01DK144194-01A1 (Concessão/Contrato do NIH dos EUA)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Computer codes developed for MRI and PET analysis will be shared on the open-access GitHub platform to support reproducibility. The study protocol and clinical data generated from this study will be uploaded to ClinicalTrials.gov. De-identified neuroimaging and research data will be submitted to appropriate NIH data repositories in compliance with NIH data sharing requirements.
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
produto fabricado e exportado dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .