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.
Přehled studie
Postavení
Podmínky
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Nan Zhai, C.R.N.P.
- Telefonní číslo: (301) 827-3324
- E-mail: nan.zhai@nih.gov
Studijní záloha kontaktů
- Jméno: Valerie L Darcey
- Telefonní číslo: (301) 402-9689
- E-mail: valerie.darcey@nih.gov
Studijní místa
-
-
Maryland
-
Bethesda, Maryland, Spojené státy, 20892
- National Institutes of Health Clinical Center
-
Kontakt:
- Valerie Darcey
- Telefonní číslo: 301-402-9689
- E-mail: valerie.darcey@nih.gov
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
- 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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Základní věda
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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. |
|
Experimentální: 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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Dopamine D2 receptor binding potential (D2BP) during steady portion of [11C]raclopride infusion PET neuroimaging
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
The magnitude of striatal dopamine responses to orosensory and post-ingestive milkshake exposure
Časové okno: 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
Časové okno: 90-180 minutes
|
Measured while fasting and 1.3 -3 hours after a palatable liquid meal (Cohort 2). |
90-180 minutes
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Valerie L Darcey, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 10002388
- 002388-DK
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu 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.
Časový rámec sdílení IPD
Data will be made available as soon as possible or at the time of associated publication, whichever comes first
Kritéria přístupu pro sdílení 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.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- ICF
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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