Neural and Metabolic Factors in Carbohydrate Reward

NCT06053294 | Recruiting

• 1 other identifier: 19-927
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Dietary factors contributed to nearly 50% of all cardiometabolic deaths in the US in 2012, making it one of the leading causes of preventable death in the US, second only to tobacco use. Human diets and food choices can't help but be influenced by the ubiquitous availability of processed foods of high-energy density and low nutrient content, consumption of which can lead to obesity, type II diabetes, heart disease, and other types of metabolic dysfunction. Surprisingly, food reinforcement does not rely on perceived energy density. Rather food reinforcement is associated with actual energy density and therefore, on an implicit knowledge of caloric content. That implicit knowledge must have a neural signature and a mechanism by which the gut communicates nutritive value to the brain. There is evidence, at least for fat and carbohydrates, that these pathways are separable, but terminate in a common neural structure, the dorsal striatum or caudate. This could be one mechanism by which modern processed foods high in both fat and carbohydrate are so sought after and readily consumed, In fact, when experimentally tested, fat and carbohydrate combinations were more reinforcing calorie for calorie than fat or carbohydrates alone and the level of reinforcement correlated with activity in reward- related brain areas. Beyond simple reinforcing value, it is known from the literature on drugs of abuse that the faster a drug is arrives at the brain, the higher it's abuse potential, however, little is known about how the kinetics of nutrient excursion influence food preference, choice, and brain activity. This project aims to test this specifically for carbohydrate reward.

Conditions

Carbohydrate Metabolism

Outcome Measures

Primary Outcomes (1)

• Change in preference- liking

  Subjective ratings of liking of flavors used in the intervention will be 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.

  at the end of the study; 5 weeks after start of study

Secondary Outcomes (9)

• Change in preference- wanting, rated

  at the end of the study; 5 weeks after start of study

• Change in preference- wanting, ad lib intake

  at the end of the study; 5 weeks after start of study

• Change in preference- wanting, forced choice

  at the end of the study; 5 weeks after start of study

• Blood oxygen level-dependent (BOLD) response to beverages

  at the end of the study; 5 weeks after start of study

• Blood glucose response to beverages

  Each week for 3 weeks during the study

Study Arms (3)

CS- First

EXPERIMENTAL

Participants who receive the conditional stimulus (CS) - first.

Other: CS- Beverage; Other: CS+Fast; Other: CS+Slow

CS+Fast First

EXPERIMENTAL

Participants who receive the CS+Fast First

Other: CS- Beverage; Other: CS+Fast; Other: CS+Slow

CS+Slow First

EXPERIMENTAL

Participants who receive the CS+Slow First

Other: CS- Beverage; Other: CS+Fast; Other: CS+Slow

Interventions

CS- Beverage OTHER

Conditioned Stimulus - (CS-): Flavored beverage solution with sweetness-matched sucralose. Participants will consume flavored beverage solutions sweetened with sucralose to match the sweetness of 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurement over a 2-hour period. 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.

CS+Fast First; CS+Slow First; CS- First

CS+Fast OTHER

(CS+): Flavored beverage solution with 110 calories of sucrose. Participants will consume flavored beverage solutions containing 110 calories of sucrose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurement over a 2-hour period. 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.

CS+Fast First; CS+Slow First; CS- First

CS+Slow OTHER

(CS+): Flavored beverage solution with 110 calories of maltodextrin. Participants will consume flavored beverage solutions containing 110 calories of maltodexrin in 6 exposure sessions within 1 week.One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurement over a 2-hour period. 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.

CS+Fast First; CS+Slow First; CS- First

Eligibility Criteria

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

You may qualify if:

• BMI between 18.5-30 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

You may not qualify if:

• Current inhaled nicotine use
• History of alcohol dependence.
• Current or past diagnosis of diabetes or thyroid problems.
• Taking medications known to influence study measures (including antiglycemic agents, thyroid medications, sleep medications)
• Active medical or neurologic disorder.
• 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 MRI, including pacemaker, aneurysm clips, neurostimulators, cochlear or other implants, metal in eyes, regular work with steel, etc.

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead

Study Sites (1)

Fralin Biomedical Research Institute at VTC

Roanoke, Virginia, 24016, United States

RECRUITING

Related Publications (1)

• Kelly AL, Baugh ME, Ahrens ML, Valle AN, Sullivan RM, Oster ME, Fowler ME, Carter BE, Davy BM, Hanlon AL, DiFeliceantonio AG. Neural and metabolic factors in carbohydrate reward: Rationale, design, and methods for a flavor-nutrient learning paradigm in humans. Contemp Clin Trials. 2024 Dec;147:107717. doi: 10.1016/j.cct.2024.107717. Epub 2024 Oct 15.

  PMID: 39413990 DERIVED

Central Study Contacts

Alexandra G DiFeliceantonio, PhD

CONTACT

5405262285; dife@vt.edu

Study Design

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

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: September 25, 2023
• Study Start: May 1, 2023
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

US (1)