Neural and Metabolic Factors in Carbohydrate Reward

NCT ID: NCT06053294

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-01
• Study Completion Date: 2029-05-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

CS- First

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

Group Type: EXPERIMENTAL

CS- Beverage

Intervention Type: 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

Intervention Type: 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+Slow

Intervention Type: 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

Participants who receive the CS+Fast First

Group Type: EXPERIMENTAL

CS- Beverage

Intervention Type: 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

Intervention Type: 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+Slow

Intervention Type: 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+Slow First

Participants who receive the CS+Slow First

Group Type: EXPERIMENTAL

CS- Beverage

Intervention Type: 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

Intervention Type: 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+Slow

Intervention Type: 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.

Interventions

CS- Beverage

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.

Intervention Type: OTHER

CS+Fast

(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.

Intervention Type: OTHER

CS+Slow

(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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. BMI between 18.5-30 kg/m2

2. Not pregnant or planning to become pregnant during study participation

3. Residing in the Roanoke area and/or willing/able to attend sessions at the Fralin Biomedical Research Institute

4. Able to speak and write in English

Exclusion Criteria

1. Current inhaled nicotine use

2. History of alcohol dependence.

3. Current or past diagnosis of diabetes or thyroid problems.

4. Taking medications known to influence study measures (including antiglycemic agents, thyroid medications, sleep medications)

5. Active medical or neurologic disorder.

6. Current shift work (typical pattern of work/activity overnight)

7. Previous weight loss surgery

8. Adherence to a special diet within the past 3 months (e.g., low-carb or ketogenic diet, exclusion of food groups/specific macronutrients, intermittent fasting, etc.)

9. Allergy to any food or ingredient included in the study diets, meals, or beverages

10. Currently pregnant or planning to become pregnant during study participation

11. Claustrophobia

12. Contraindications for MRI, including pacemaker, aneurysm clips, neurostimulators, cochlear or other implants, metal in eyes, regular work with steel, etc.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Virginia Polytechnic Institute and State University

OTHER

Sponsor Role: lead

Responsible Party

Alexandra DiFeliceantonio

Assitant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fralin Biomedical Research Institute at VTC

Roanoke, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alexandra G DiFeliceantonio, PhD

Role: CONTACT

dife@vt.edu

5405262285

Facility Contacts

Alexandra G DiFeliceantonio, PhD

Role: primary

dife@vt.edu

540-526-2285

References

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.

Reference Type: DERIVED

PMID: 39413990 (View on PubMed)

Other Identifiers

19-927

Identifier Type: -

Identifier Source: org_study_id