Clinical trial NCT06165952: Effects of Processed Foods on Brain Reward Circuitry and Food Cue Learning
Official title: Effects of Processed Foods on Brain Reward Circuitry and Food Cue Learning
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ultra-processed Foods (UP)
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
name: Oregon Research Institute
First posted: 2023-12-12
Enrollment: 162
Sex: ALL
Minimum age (years): 13
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community sample

Brief summary: Examine if ultra-processed (UP) foods are more effective in activating reward, attention, and memory brain regions and in promoting food cue learning than minimally-processed foods. Assess individual differences in neurobehavioral responses to UP foods.

Detailed description: Obesity is the second leading cause of premature death. Consumption of ultra-processed foods is theorized to be a key cause of obesity. Ultra-processed foods are formulations of cheap industrial sources of dietary energy and nutrients plus additives such as fat, sugar, and flavors that enhance acceptability of the foods.

A cross-over experiment with overweight adults found that ad lib access to an ultra-processed diet for 2-weeks resulted in increased caloric intake (508 kcal/day) and more weight gain versus ad lib access to a minimally-processed diet matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. The fact that ad lib access to ultra-processed foods resulted in a large increase in caloric intake and weight gain implies that ultra-processed foods may more effectively activate brain regions implicated in reward processing, attention/salience, and memory that influence eating behavior.

However, no brain imaging study has experimentally tested whether ultra-processed foods are more effective in activating brain regions implicated in reward, attention, and memory than minimally-processed foods or experimentally investigated the relative role of the elevated caloric density versus the flavor enhancers of ultra-processed foods in driving greater activation of these brain regions. Preliminary data showed that tastes of ultra-processed high-calorie chocolate milkshake produced greater activation in regions implicated in reward valuation (caudate, nucleus accumbens), attention/salience (precuneus), and memory retrieval (medial temporal gyrus, dorsomedial prefrontal cortex) than tastes of ultra-processed low-calorie chocolate milkshake.

The investigators propose to evaluate the efficacy of ultra-processed foods to activate reward, attention, and memory regions compared to minimally-processed foods, investigate the relative role of the higher caloric content versus the flavor additives/enhancers of ultra-processed foods to engage this circuitry using a 2 x 2 experimental design, test whether ultra-processed foods are more effective in increasing the incentive salience of food cues than minimally-processed foods, which is important because elevated reward region response to food cues/images increases risk for excess weight gain, and test whether individuals who show the greatest responsivity of reward, attention, and memory regions to ultra-processed foods and stronger food reward cue learning are at risk for greater ad lib intake of ultra-processed foods and future body fat gain.

Aim 1: Test the hypothesis that tastes, anticipated tastes, and images of ultra-processed foods activate reward, attention, and memory brain regions more than tastes, anticipated tastes, and images of minimally-processed foods, and evaluate the relative role of the higher caloric content versus flavor additives/enhancers in activating these regions using a 2 x 2 experimental design.

Aim 2: Test the hypothesis that ultra-processed foods foster stronger learning of cues that predict impending tastes of ultra-processed foods than minimally-processed foods, reflected by greater increases in striatal response over the course of cue exposure and quicker responses to cues for tastes of ultra-processed foods.

Aim 3: Test the hypothesis that participants who show greater activation in reward/attention/memory regions in response to tastes, anticipated tastes, and images of ultra-processed foods will consume more ultra-processed foods ad libitum (Aim 3a) and show greater future body fat gain (Aim 3b). Exploratory analyses will establish neural fingerprints that predict ad lib intake of ultra-processed foods and body fat gain (Aim 3c).

Aim 4: Test the hypothesis that participants who show the most pronounced reward cue learning in response to ultra-processed foods will consume more ultra-processed foods ad libitum (Aim 4a) and show greater future body fat gain (Aim 4b).

Eligibility criteria: Inclusion Criteria:

* female and male adolescents 13-15 years of age
* age- and sex- adjusted zBMI scores between the 25th and 75th percentile
* participant and their guardian must be able to read and speak English to gather valid consent

Exclusion Criteria:

* current eating disorders or other major psychiatric disorders (e.g., depression, bipolar, schizophrenia, substance use disorder)
* fMRI contra-indicators (e.g., metal implants, braces, claustrophobia, pregnancy)
* serious medical problems (e.g., Type 2 diabetes, cancer)
* history of food allergies or restrictive dietary requirements (e.g., lactose intolerance, vegan)
* use of psychoactive drugs more than once weekly
* medications that impact appetite or reward functioning (e.g., metformin, anti-psychotic medication, insulin)

Primary outcomes:
measure: Body Fat
timeFrame: Baseline, 1-year, 2-year, 3-year, 4-year follow-up
measure: Baseline functional magnetic resonance imaging (fMRI) Ultra-Processed Foods Taste, Anticipated Taste, and Picture Paradigm
timeFrame: Baseline
measure: Baseline fMRI Ultra-Processed Food Picture Paradigm
timeFrame: Baseline
measure: Baseline fMRI Ultra-Processed Food Cue Learning Paradigm
timeFrame: Baseline
measure: Baseline Post-fMRI Ad Lib Food Intake
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Eric Stice, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hall KD, Ayuketah A, Brychta R, Cai H, Cassimatis T, Chen KY, Chung ST, Costa E, Courville A, Darcey V, Fletcher LA, Forde CG, Gharib AM, Guo J, Howard R, Joseph PV, McGehee S, Ouwerkerk R, Raisinger K, Rozga I, Stagliano M, Walter M, Walter PJ, Yang S, Zhou M. Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell Metab. 2019 Jul 2;30(1):67-77.e3. doi: 10.1016/j.cmet.2019.05.008. Epub 2019 May 16.
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citation: Stice E, Yokum S, Rohde P, Cloud K, Desjardins CD. Comparing healthy adolescent females with and without parental history of eating pathology on neural responsivity to food and thin models and other potential risk factors. J Abnorm Psychol. 2021 Aug;130(6):608-619. doi: 10.1037/abn0000686.
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