Ultra Crave: An Investigation of Ultra-Processed Food

Study Overview
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Brief Summary
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This study experimentally investigates whether a reduction in ultra-processed (UP) food intake (1) causes aversive withdrawal symptoms in humans, (2) increases the motivational salience of UP food cues and, if so, (3) whether these factors undermine the ability to adhere to a low-UP diet. The following aims and hypotheses are tested: Aim 1: To investigate whether aversive physical, cognitive, and affective withdrawal symptoms emerge in response to reduced UP food intake compared to a calorically equivalent high-UP diet, and whether this predicts failure to adhere to a low-UP diet. H1a: Reducing UP food intake will result in aversive physical, cognitive, and affective withdrawal symptoms, as indicated by 1) ecological momentary assessment (EMA) reports of aversive withdrawal symptoms, and 2) heart rate reactivity and subjective distress to an in-lab stressor. H1b: Aversive symptoms of UP food withdrawal will predict greater UP food intake and higher blood glucose levels when trying to adhere to a low UP diet. Aim 2: To investigate whether increased motivational salience of UP food cues emerges in response to reduced UP food intake, and whether this predicts failure to maintain a low-UP diet. H2a: Reducing UP food intake will result in increased motivational salience of UP food cues, as indicated by 1) EMA reports of UP food craving, 2) heart rate reactivity and subjective craving in a simulated fast-food restaurant, 3) heightened reinforcement value for UP food relative to other reinforcers, and 4) greater reward-related neural response to UP food cues. H2b: Increased motivational salience of UP food cues will predict greater UP food intake and higher blood glucose levels when trying to adhere to a low UP diet.

Detailed Description
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The study will include a combination of in-person, at-home, and virtual activities over the course of  22 days (contingent on scheduling, this duration may vary and particularly between in-person visits #1 and #2). Participants complete three in-lab visits, each followed by a week of remote data tasks (e.g., remote food photography, EMA, continuous glucose monitoring, and physical activity and sleep tracking (Fitbit). During in-lab visit #1, participants will complete questionnaires, behavioral tasks, and interviews, and will have body composition measurements taken (height, weight, Inbody scan). Participants will complete the remote tasks for the following week while eating their typical diet (i.e., baseline period). During in-lab visit #2, participants will complete questionnaires, interviews, and body composition measurements (height, weight, Inbody scan). Participants are randomly assigned to a high or low UP food condition and will be provided with food and beverages consistent with their condition, which they are required to exclusively consume during week 2 of remote data collection (i.e., dietary intervention period). During in-lab visit #3, participants will complete questionnaires, behavioral tasks, body composition measurements (height, weight, InBody scan), and an fMRI scan. All participants are provided with dietary instructions for a low UP diet to follow on their own during week 3 of remote data collection (i.e., dietary adherence period). At the end of the third week of remote data collection, participants are asked to complete additional questionnaires, provide information about their current diet, and complete a remote interview about their experience with the study. Participants are contacted 1- and 3-months later to complete a short follow-up survey and provide information about their current diet.

Official Title
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Ultra Crave: A Biopsychobehavioral Investigation of Withdrawal From Ultra-Processed Food in Humans

Conditions
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Food Addiction

Intervention / Treatment
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* Other: Dietary change (low ultra-processed food)
* Other: Dietary change (high ultra-processed food)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 25 to 60 years of age English-speaking Must own an Android or iPhone Smartphone Live within a 1-hour radius of the laboratory endorsement of > 4 symptoms on the YFAS 2.0 completed during eligibility screener; at the time of consent, symptom count must remain above threshold for food addiction (this discrepany is based on a previously found tendency during pilot testing to overestimate food addiction symptoms at the time of screening) endorse daily intake of multiple UP foods likes chocolate milkshake (fMRI) willing to follow dietary instructions provided by team willing to come to lab 3 times Exclusion Criteria: participants with a self-reported BMI < 18.5 and > 40 current diagnoses of disorders that can impact reward, metabolic functioning, or the ability to complete the imaging protocol (e.g., seizures, Tourette's, cancer, Irritable bowel syndrome, Inflammatory bowel disease, Hypothyroidism, substance use disorder, ADHD) Type 1 or Type 2 diabetes, pre-diabetes, hypoclycemia history of food allergies or restrictive dietary requirements (e.g., vegan) medications that impact appetite or reward functioning (e.g., anti-psychotic medication, insulin) history of diagnosis of a severe mental illness (e.g., bipolar, schizophrenia, psychotic disorder) a diagnosis of a restrictive eating disorder (anorexia nervosa, bulimia nervosa, purging disorder) within the last 5 years more than a 20-pound weight fluctuation in the last three months prior weight loss surgery (e.g., bariatric surgery) current pregnancy, breast-feeding, trying to get pregnant, or within six months of having given birth high levels of caffeine (i.e., average daily intake over 600mg) intake use of tobacco, nicotine, cannabis products within the past month and/or unwillingness to abstain from these substances during the main portion of the study high-risk alcohol use (based on the AUDIT) high levels of picky eating fMRI contraindications (e.g., claustrophobia, metal implants) red/green color blindness frequent (i.e., weekly) night shift work or irregular shifts and for abnormal sleep patterns (i.e., wake up time after 11am) inability to complete a random report within 90 minutes THC Cannabis within the past week

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-method, within subjects, perspectives, experimental design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low UP Food Diet<br> | Other: Dietary change (low ultra-processed food)<br>* This study incorporates within- and between-subject comparisons. All participants complete a series of three in-lab visits with remote data collection: Visit 1 and the following week comprise the baseline assessment period. Visit 2 and the following week comprise the dietary intervention period. Food is provided by the study team for 7 days in accordance with a low UP diet. Visit 3 and the following week comprise the dietary adherence period, during which all participants receive instructions for a low UP diet to follow on their own. All participants will complete remote assessments at 1 week, 1 month, and 3 month follow-up.<br>|
| Active Comparator: High UP Food Diet<br> | Other: Dietary change (high ultra-processed food)<br>* Visit 1 and the following week comprise the baseline assessment period. Visit 2 and the following week comprise the dietary intervention period. Food is provided by the study team for 7 days in accordance with a high UP diet. Visit 3 and the following week comprise the dietary adherence period, during which all participants receive instructions for a low UP diet to follow on their own. All participants will complete remote assessments at 1 week, 1 month, and 3 month follow-up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Withdrawal Symptoms | Withdrawal symptoms (e.g., anger, anxiety) will be assessed using ecological momentary assessment (EMA) on a scale from 1 (not at all) to 7 (extremely); higher scores indicate greater withdrawal symptoms. | Assessed during dietary intervention period for 1 week | 
| Craving of ultra-processed (UP) foods | Craving of UP foods will be assessed using EMA on a scale from 1 (not at all) to 7 (extremely); higher scores indicate greater craving of UP foods. | Assessed during dietary intervention period for 1 week | 
| Low UP food intake | Intake of low UP foods will be assessed using remote food photography method. | Assessed during dietary adherence period for 1 week | 
| Self-Reported Low UP food intake | Intake of low UP foods will be assessed using EMA reports of food intake. Responses will be coded into high and low UP food intake based on the NOVA classification. | Assessed during dietary adherence period for 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactivity to a stressor | Stress reactivity will be assessed using an in-lab stress task that has participants listen to an audio recording of a current stressor in their life. Participants' heart rate in response to the audio recording, relative to a baseline measurement, will be used as an indicator of stress reactivity; an increase in heart rate will be indicative of greater stress reactivity. | Assessed post-dietary change during in-lab Visit 3 (1 day) | 
| Self-reported reactivity to a stressor | Stress reactivity will be assessed using an in-lab stress task that has participants listen to an audio recording of a current stressor in their life. Participants' subjective ratings of reactivity will be assessed at baseline (prior to listening to the audio recording) and immediately after listening to the audio recording using the negative affect subscale from the Positive and Negative Affect Schedule (PANAS); each item is rated on a 1 (very slightly or not at all) to 5 (extremely) scale, with higher numbers indicating greater experienced affect; an increase in score, relative to baseline, will indicate greater stress reactivity. | Assessed post-dietary change during in-lab Visit 3 (1 day) | 
| Cue reactivity to a simulated fast food restaurant | Participants will spend 5 minutes in a simulated fast food restaurant. Participants' heart rate in response to the simulated fast food restaurant, relative to a baseline measurement, will be used as an indicator of cue reactivity; increases in will be indicative of greater cue reactivity. | Assessed post-dietary change during in-lab Visit 3 (1 day) | 
| Self-reported cue reactivity to a simulated fast food restaurant | Participants will spend 5 minutes in a simulated fast food restaurant. Participants' subjective craving will be assessed at baseline (prior to entering the restaurant) and while in the restaurant on a scale from 0 (no craving at all) to 100 (I have never craved food more), with greater numbers indicating higher craving; an increase in score, relative to baseline, will indicate greater cue reactivity. | Assessed post-dietary change during in-lab Visit 3 (1 day) | 
| Level of reinforcement value for ultra processed foods | Participants will complete a computerized task that measures their willingness to work (i.e., reinforcement value) for a UP food gift card relative to a non-food gift card. | Baseline assessed during in-lab Visit 1 (1 day); assessed again post-dietary change during in-lab Visit 3 (1 day) | 
| Magnitude of neural reward-related response to tasting a milkshake | Participants will complete an fMRI paradigm where they see a UP food cue (i.e., picture of a chocolate milkshake) that predict receipt of a UP food (i.e., a chocolate milkshake). The paradigm also includes a control cue (i.e., picture of a water glass) that predicts receipt of a tasteless solution (which contains the ionic components of saliva; 25 mM KCl and 2.5 mM NaHCO3 in distilled water). Participants' activation in neural regions associated with reward (e.g., mOFC, striatum) to the milkshake cue (relative to the water cue) will be used as a measure of increased reward-related response to UP food cues. | Assessed post-dietary change during in-lab Visit 3 (1 day) | 
| Blood Glucose Level | Assessed using a continuous blood glucose monitor. | Assessed during dietary adherence period for 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Withdrawal, Food Addiction, Highly Processed Foods