Effects of Ad Libitum Ultra-Processed Diet on Brain Dopamine in Humans
Background:
Dopamine is a chemical that the brain makes when a person expects a reward. Researchers want to learn more about how eating different types of food affects dopamine levels in the brain.
Objective:
To test how eating different foods affects dopamine levels in the brains of healthy people.
Eligibility:
Healthy people aged 18 to 45 years old.
Design:
Participants will be divided into 2 groups (cohorts). Both will have overnight stays in the clinic.
All participants will be screened. They will talk to a dietitian about their eating habits. They will have a test of how much energy their body uses: They will lie on a table with a clear hood over their heads to measure the gases as they breathe.
During the 3 weeks before participants stay at the clinic, a dietitian will call at 3 random times to ask what they ate the day before. They will complete questionnaires. Cohort 1 will wear a device to track their step count for at least 7 days; these participants will be given food to eat for 2 days before they stay in the clinic.
Cohort 1 will stay in the clinic for 14 days. They will eat as much or as little as they would like on 2 different diets for 5 days each and a normal diet on the other days. They will have blood collected multiple times. They will have 2 d ifferent types of imaging scans. For 1 type, they will receive a drug through a vein to show how much dopamine is in their brains.
Cohort 2 will stay in the clinic for 2 days. They will eat only the foods provided. They will have imaging scans before and after drinking a milkshake. For both scans, they will receive a drug through a vein to show how much dopamine is in their brains. They will have blood collected multiple times.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
Study Description:
In this single-site study, we will recruit a cohort of 32 adult volunteers to a randomized crossover diet study to investigate change in dopamine D2 receptor availability (via [11C]raclopride binding potential). During their participation, after a 2-day outpatient stabilization diet, participants will be admitted for a 14-day, 13-night inpatient stay at the NIH Clinical Center. Following 2 days of inpatient stabilization diet, participants will consume two ad libitum test diets with distinct proportions of ultra-processed food for 5 days each in random order separated by 1 day of stabilization diet. We will collect information via Positron Emission Tomography (PET) about dopamine D2 receptor availability under fasting conditions and dopamine response to an oral stimulus solution. Additionally, magnetic resonance spectroscopy and imaging (MRS, MRI) will be used to collect information on changes in brain GABA tone, white matter hyperintensities, brain iron content, and brain activity in response to the two test diets. Further, we will additionally recruit a cohort of 36 adult volunteers for a 2 day/1night stay at the Clinical Center to measure dopamine D2 receptor availability in the extended post ingestive state to determine whether dopamine release may be quantified in this period of the postprandial state.
Objectives:
- Primary Objective: To determine the impact of two 5-day ad libitum test diets differing in proportion of ultra-processed, energy-dense, hyper-palatable foods on fasting striatal [11C]raclopride dopamine D2 receptor binding potential (D2BP) as well as the magnitude of any change from baseline.
- Secondary Objective: To determine differences in spatiotemporal components of striatal dopamine response (rDA) to a milkshake after two 5-day ad libitum test diets matched for presented nutrients but different in proportion of ultra-processed, energy-dense, hyperpalatable foods.
- Secondary Objective: To determine change in whole striatal dopamine D2BP in the extended post-ingestive period, beginning 1.5 - 3 hours following consumption of a UPF milkshake, as measured by [11C]raclopride
Endpoints:
- Primary Endpoint: Dopamine D2 receptor binding potential (D2BP) in the striatum after two test diets will be quantified during steady state portion of 20mCi [11C]raclopride infusion PET neuroimaging.
- Secondary Endpoint: Regionally and temporally specific dopamine response to in-scanner milkshake consumption and digestion after 5 days of each test diet will be determined voxelwise (spatial) over a duration of [11C]raclopride infusion (temporal), compared to equivalent endpoints for "tasteless" oral stimulus.
- Secondary Endpoint: D2BP in the striatum will be quantified using a bolus of 20mCi [11C]raclopride in both the overnight fasted state and delayed post-ingestive state for each participant.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Nan Zhai, C.R.N.P.
- Número de teléfono: (301) 827-3324
- Correo electrónico: nan.zhai@nih.gov
Copia de seguridad de contactos de estudio
- Nombre: Valerie L Darcey
- Número de teléfono: (301) 402-9689
- Correo electrónico: valerie.darcey@nih.gov
Ubicaciones de estudio
-
-
Maryland
-
Bethesda, Maryland, Estados Unidos, 20892
- National Institutes of Health Clinical Center
-
Contacto:
- Valerie Darcey
- Número de teléfono: 301-402-9689
- Correo electrónico: valerie.darcey@nih.gov
-
-
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
- INCLUSION CRITERIA
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
-
Aged 18 to 45 years old
-
In good general health as evidenced by medical history
-
Weight stable (< +/- 5% change in last 6 months), based on self-report
-
BMI
- Cohort 1: 18.5 - 24.9 kg/m^2
- Cohort 2: >= 18.5 kg/m^2
EXCLUSION CRITERIA
An individual who meets any of the following criteria will be excluded from participation in this study:
- Body weight > 400 lbs. (weight limit of PET scanner)
- History or current self-report of conditions that may influence appetite, in the opinion of the study investigators, including but not limited to cancer, diabetes mellitus, evidence of metabolic dysfunction, changes in senses of smell or taste (e.g., covid-related), or metabolic/bariatric surgery
- History or current neurological, mood, eating, or substance use disorders by self-report, history/physical, Eating Disorder Examination Questionnaire, and/or DSM-5 Cross-cutting symptom measure.
- Measured resting energy expenditure +/- 30% of that predicted by Mifflin St-Jeor equation.
- Uncontrolled hypertension, with blood pressure >140/90 mm Hg
- Pregnancy or lactation
- Known allergic reactions to components of the PET agent, [C-11] raclopride.
- Having had previous radiation exposure within the last year for either medical or research purposes (e.g. X-rays, PET scans, etc.) that would exceed research limits. Excessive radiation exposure will be determined at the discretion of the PI and/or study team
- Inability or unwillingness (e.g. due to claustrophobia) to tolerate lying flat on their back for extended periods of time in PET/MR or MRI scanner or (Cohort 1 only) inability to tolerate swallowing drops of liquid delivered onto tongue while lying down on bed.
- Having metal implants incompatible with MRI (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).
- Left-handedness, by self-report and confirmation via Edinburgh Handedness Survey
- Self-report of daily alcohol intake > 3 drinks (males) or > 2 drinks (females)
- Current nicotine use (e.g. cigarette, vaping) determined by participant report or nicotine dependence confirmed by Fagerstrom Nicotine Dependence (score >= 4)
- Current use of medications or drugs of abuse which may influence appetite or have central effects, in the opinion of study investigators
- Caffeine consumption > 300 mg/day (roughly >=3 cups coffee or 2-3 energy drinks)
- Significant dietary restrictions, based on evaluation by nutrition staff and results of nutrition screener (rating fewer than 75% of foods listed as a 4 or higher score on The Food Enjoyment Questionnaire)
- Unable or unwilling to provide informed consent
- Unable or unwilling to adhere to study diet, procedures, schedule, and lifestyle considerations
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Ciencia básica
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Experimental: MPF-UPF
Participants will be randomized to the one of two diet sequences (study arms: UPF-MPF vs MPF-UPF) by NIH dietitians after enrollment, in advance of admission. A total of n=32 participants will be evenly grouped into 16 batches according to date of inpatient admission. Within each batch of 2 participants, participants will be randomly assigned to one of the two diet sequences, ensuring any order effects will be counterbalanced and maintaining balance across diet sequence assignments. |
The drug is intended for use as a radiopharmaceutical for positron emission tomography (PET) administered at a maximum prescribed dose of 20mCi and will be administered intravenously via indwelling catheter The ~8 oz liquid meal will be high in both dietary fat and sugar and ultra-processed designation based on ingredients and will be prepared by the NIH Clinical Center Metabolic Kitchen for participant consumption during the PET scans at the end of both test dietary intervention periods (Cohort 1) or for consumption between the PET scans (Cohort 2). The control stimulus is a non-rewarding tasteless solution with viscosity distinct from pure water (i.e., artificial saliva). Four dilutions of 25mM potassium chloride + 2.5mM sodium bicarbonate will be prepared by NIH Clinical Center Pharmacy for participant oral stimulus taste test The minimally processed diet will derive ~80% of calories from minimally processed foods and will contain no ultra-processed foods, (NOVA 1-3), as defined by the degree, extent, and purpose of processing according to the NOVA classification system. The minimally processed diet will be matched to the ultra-processed diet for presented macronutrients, sugar, sodium, and fiber. This diet will be low in both non-beverage energy density and hyper-palatable foods The baseline (control) diet will be composed of 50% of energy from ultra-processed foods while matching distribution of macronutrients presented in test diets and total sugar, sodium, and fiber). Energy needs will be estimated using resting energy expenditure multiplied by an appropriate activity factor collected at screening visit to facilitate production by the NIH Metabolic Kitchen. |
|
Experimental: UPF-MPF
Participants will be randomized to the one of two diet sequences (study arms: UPF-MPF vs MPF-UPF) by NIH dietitians after enrollment, in advance of admission. A total of n=32 participants will be evenly grouped into 16 batches according to date of inpatient admission. Within each batch of 2 participants, participants will be randomly assigned to one of the two diet sequences, ensuring any order effects will be counterbalanced and maintaining balance across diet sequence assignments. |
The drug is intended for use as a radiopharmaceutical for positron emission tomography (PET) administered at a maximum prescribed dose of 20mCi and will be administered intravenously via indwelling catheter The ~8 oz liquid meal will be high in both dietary fat and sugar and ultra-processed designation based on ingredients and will be prepared by the NIH Clinical Center Metabolic Kitchen for participant consumption during the PET scans at the end of both test dietary intervention periods (Cohort 1) or for consumption between the PET scans (Cohort 2). The control stimulus is a non-rewarding tasteless solution with viscosity distinct from pure water (i.e., artificial saliva). Four dilutions of 25mM potassium chloride + 2.5mM sodium bicarbonate will be prepared by NIH Clinical Center Pharmacy for participant oral stimulus taste test The baseline (control) diet will be composed of 50% of energy from ultra-processed foods while matching distribution of macronutrients presented in test diets and total sugar, sodium, and fiber). Energy needs will be estimated using resting energy expenditure multiplied by an appropriate activity factor collected at screening visit to facilitate production by the NIH Metabolic Kitchen. The ultra-processed diet will derive ~80% of energy from ultra-processed foods (NOVA 4), as defined by the degree, extent, and purpose of processing according to the NOVA classification system. The ultra processed diet will be matched to the minimally processed diet for presented macronutrients, sugar, sodium, and fiber. This diet will be high in both non-beverage energy density and hyper-palatable foods. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Dopamine D2 receptor binding potential (D2BP) during steady portion of [11C]raclopride infusion PET neuroimaging
Periodo de tiempo: 5 days
|
Fasting (steady state) whole striatal dopamine D2 receptor binding at the conclusion of three diet periods (on 4th day of control diet, after 5 full days ad libitum UPF, and after 5 full days ad libitum MPF) |
5 days
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
The magnitude of striatal dopamine responses to orosensory and post-ingestive milkshake exposure
Periodo de tiempo: 5 days
|
Measured at the conclusion of three diet periods (on 4th day of control diet, after 5 full days ad libitum UPF, and after 5 full days ad libitum MPF). |
5 days
|
|
The difference between striatal dopamine D2 receptor binding potential
Periodo de tiempo: 90-180 minutes
|
Measured while fasting and 1.3 -3 hours after a palatable liquid meal (Cohort 2). |
90-180 minutes
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Investigadores
Investigadores
- Investigador principal: Valerie L Darcey, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- 10002388
- 002388-DK
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Data published in Harvard Dataverse (https://dataverse.harvard.edu/) will be accessible to the research community for the long-term. Terms of access to data to require requestors to log in and provide information including their identity and intended use to initiate an access request to Dr. Darcey, the PI.
Marco de tiempo para compartir IPD
Data will be made available as soon as possible or at the time of associated publication, whichever comes first
Criterios de acceso compartido de IPD
Terms of access to data to require requestors to log in and provide information including their identity and intended use to initiate an access request to Dr. Darcey, the PI.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- CIF
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .