The Role of Altered Nutrient Partitioning in Food Reward

NCT05200845 | Completed Results

• 1 other identifier: 21-964
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity remains a public health epidemic despite substantial advances in treatment strategies and therapies in the last decade. Effective strategies to support maintenance of improved metabolic health and reduced body weight are still needed. Signals from the gut to the brain are important in regulating metabolism and energy balance and have been linked with food reward and preference in metabolically healthy individuals with normal body mass index. In particular, post-ingestive signaling related to glucose metabolism has been linked with food reward and preference. However, not much is known about how these gut and brain signals interact to influence eating behaviors in states of obesity or altered metabolic health. In addition, evidence in rodent models and human studies indicates obesity is associated with a blunted brain response to foods compared with normal body weight. However, whether altered nutrient utilization, termed metabolic inflexibility, influences the relationship between obesity and food reward has yet to be studied. The overall objective of this proof-of-concept pilot study is to assess the feasibility of measuring reward response following a flavor-nutrient conditioning paradigm across the normal to obese body mass index (BMI) range and in states of altered metabolic health. The aims of this study are: 1) to determine whether differences in reinforcement learning/flavor-nutrient conditioning of carbohydrate can be measured across the body mass index range; and 2) to determine the feasibility of assessing metabolic flexibility and whether a relationship between metabolic flexibility and calorie-predictive reward can be detected.

Conditions

Overweight and Obesity

Outcome Measures

Primary Outcomes (1)

• Change in Preference- Liking

  Subjective ratings of liking of flavors used in the intervention were assessed at baseline and after the intervention. The generalized Labeled Magnitude Scale will be used. The scale is anchored by descriptors of "Most Disliked Sensation Imaginable" and "Most Liked Sensation Imaginable" at the lower and upper ends, respectively. The score is determined by the place on the scale participants select (range of scale is 0-100). An increase in score from baseline to post-intervention indicates an increase in liking.

  Baseline and at 4 weeks

Secondary Outcomes (10)

• Post-test Preference - Wanting

  Baseline and at 4 weeks

• Change in Preference- Wanting

  30-minute measurement

• Change in Preference- Wanting

  5-minute measurement

• Blood Oxygen Level-dependent (BOLD) Response to Beverages

  30-minute measurement that occurs during the post-test, approximately 4 weeks after the first study session

• Substrate Oxidation Response to Test Meals

  6-hour measurement

Study Arms (4)

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal

EXPERIMENTAL

Participants will undergo exposure sessions with flavored beverage solutions containing sucrose first. Then, they will undergo exposure sessions with flavored beverages containing sucralose. Participants will undergo the high fat meal test session inside the metabolic chamber first. Then they will undergo the high carbohydrate test meal session.

Other: Conditioned Stimulus + (CS+): Flavored beverage solution with 75 calories of sucrose; Other: Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose; Other: High-Fat Test Meal Inside a Metabolic Chamber; Other: High-Carbohydrate Test Meal Inside a Metabolic Chamber; Other: fMRI Scan

Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal

EXPERIMENTAL

Participants will undergo exposure sessions with flavored beverage solutions containing sucralose first. Then, they will undergo exposure sessions with flavored beverages containing sucrose. Participants will undergo the high fat meal test session inside the metabolic chamber first. Then they will undergo the high carbohydrate test meal session.

Other: Conditioned Stimulus + (CS+): Flavored beverage solution with 75 calories of sucrose; Other: Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose; Other: High-Fat Test Meal Inside a Metabolic Chamber; Other: High-Carbohydrate Test Meal Inside a Metabolic Chamber; Other: fMRI Scan

Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

EXPERIMENTAL

Participants will undergo exposure sessions with flavored beverage solutions containing sucralose first. Then, they will undergo exposure sessions with flavored beverages containing sucrose. Participants will undergo the high carbohydrate meal test session inside the metabolic chamber first. Then they will undergo the high fat test meal session.

Other: Conditioned Stimulus + (CS+): Flavored beverage solution with 75 calories of sucrose; Other: Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose; Other: High-Fat Test Meal Inside a Metabolic Chamber; Other: High-Carbohydrate Test Meal Inside a Metabolic Chamber; Other: fMRI Scan

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal

EXPERIMENTAL

Participants will undergo exposure sessions with flavored beverage solutions containing sucrose first. Then, they will undergo exposure sessions with flavored beverages containing sucralose. Participants will undergo the high carbohydrate meal test session inside the metabolic chamber first. Then they will undergo the high fat test meal session.

Other: Conditioned Stimulus + (CS+): Flavored beverage solution with 75 calories of sucrose; Other: Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose; Other: High-Fat Test Meal Inside a Metabolic Chamber; Other: High-Carbohydrate Test Meal Inside a Metabolic Chamber; Other: fMRI Scan

Interventions

Conditioned Stimulus + (CS+): Flavored beverage solution with 75 calories of sucrose OTHER

Participants will consume flavored beverage solutions containing 75 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws over a 2-hour period, and one exposure session will include indirect calorimetry measurement pre- and post-consumption. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal; Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose OTHER

Participants will consume flavored beverage solutions sweetened with sucralose to match the sweetness of 75 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws over a 2-hour period, and one exposure session will include indirect calorimetry measurement pre- and post-consumption. The other 4 exposure sessions will occur at specified times outside the laboratory sessions. Subjective ratings of internal state (i.e., hunger, fullness, and thirst) will be collected throughout each exposure. Subjective ratings of liking and wanting of each beverage will also be assessed.

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal; Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

High-Fat Test Meal Inside a Metabolic Chamber OTHER

A high-fat test meal (60% fat, 20% carbohydrate) will be provided after a 1-hour baseline measurement of substrate oxidation during a 6-hour metabolic chamber stay. Postprandial substrate oxidation will be measured for 5 hours.

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal; Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

High-Carbohydrate Test Meal Inside a Metabolic Chamber OTHER

A high-carbohydrate test meal (60% carbohydrate, 20% fat) will be provided after a 1-hour baseline measurement of substrate oxidation during a 6-hour metabolic chamber stay. Postprandial substrate oxidation will be measured for 5 hours.

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal; Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

fMRI Scan OTHER

A subset of participants with BMI \> 25 will be invited to complete an functional magnetic resonance imaging (fMRI) scan as a feasibility measure. fMRI scans will be performed while beverages (without calories) used during the intervention are delivered through a custom manifold fitted to a head coil and connected to a pump system that allows precisely timed and measured delivery of liquids. Because this is feasibility-based measure, the outcome is a count of participants who completed this task.

Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Carb Meal Then High Fat Meal; Conditioned Stimulus+ (CS+) Then Conditioned Stimulus- (CS-), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-) Then Conditioned Stimulus+ (CS+), and High Fat Meal Then High Carb Meal; Conditioned Stimulus- (CS-)Then Conditioned Stimulus+ (CS+) and High Carb Meal Then High Fat Meal

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI between 18.5-40 kg/m2
• Not pregnant or planning to become pregnant during study participation
• Residing in the Roanoke area and/or willing/able to attend sessions at the Fralin Biomedical Research Institute
• Able to speak and write in English
• Specific to fMRI scan only: BMI between 25-35 kg/m2

You may not qualify if:

• Current inhaled nicotine use
• History of alcohol dependence.
• Current or past diagnosis of diabetes or thyroid problems.
• Glycated hemoglobin (Hemoglobin A1C) \>5.7%
• Taking medications known to influence study measures (including antiglycemic agents, thyroid medications, sleep medications)
• Active medical or neurologic disorder.
• Recent change in body weight (gain or loss of \> 5 lbs within the past 3 months)
• Current shift work (typical pattern of work/activity overnight)
• Previous weight loss surgery
• Allergy to any food or ingredient included in the study diets, meals, or beverages
• Currently pregnant or planning to become pregnant during study participation
• Claustrophobia
• Contraindications for bioelectrical impedance analysis, specifically implanted devices

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Fralin Biomedical Research Institute at Virginia Tech Carilion

Roanoke, Virginia, 24016, United States

Location

MeSH Terms

Conditions

Overweight; Obesity

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexandra DiFeliceantonio
• Organization: Virginia Tech

dife@vt.edu

540-526-2285

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 21, 2022
• Study Start: February 23, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: September 8, 2025
• Results First Posted: February 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)