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Completed

NCT Number: NCT05200845

The Role of Altered Nutrient Partitioning in Food Reward

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.

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Key information

Conditions

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

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Fralin Biomedical Research Institute at Virginia Tech Carilion

Roanoke, Virginia, 24016, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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.)
  • 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. (Note: This is an fMRI-specific exclusion criterion. Participants may be allowed to participate in all other study sessions and measures that do not involve fMRI.)
  • Contraindications for bioelectrical impedance analysis, specifically implanted devices

Treatment and study plan

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-): 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.

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.

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.

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.

Primary outcomes

  1. Change in Preference- Liking

    Time frame: Baseline and at 4 weeks

    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.

Secondary outcomes

  1. Post-test Preference - Wanting

    Time frame: Baseline and at 4 weeks

    Subjective ratings of wanting of flavors used in the intervention will be assessed at baseline and after the intervention. A Visual Analog Scale will be used. Participants select a place on the line that corresponds with their subjective rating, and the score is determined by the place selected (range of scores is 0-100). The line is anchored by polar opposite descriptors ("Do not want at all" and "Want very much"). An increase in score from baseline to post-intervention indicates and increase in wanting.

  2. Change in Preference- Wanting

    Time frame: 30-minute measurement

    Ad libitum intake will be used as a measure of wanting in a post-test session. Participants will be provided each beverage used during the intervention and asked to drink as much or as little of them as they would like over a 30-minute period. Total beverage intake over 30 minutes is reported as the outcome.

  3. Change in Preference- Wanting

    Time frame: 5-minute measurement

    Forced choice will be used as a measure of wanting in a post-test session. Participants will be provided each of the beverages used during the intervention and asked to choose 1 to take home with them. The outcome variable is a count of number of participants who chose each beverage condition during the forced choice test.

  4. Blood Oxygen Level-dependent (BOLD) Response to Beverages

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

    In a post-test session, functional magnetic resonance imaging (fMRI) scans were performed while beverages (without calories) used during the intervention and a tasteless solution 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. Only participants with BMI > 25 were invited to complete this portion of the study, per our protocol. In total, participants receive the CS+, CS-, and tasteless (control) solutions 24 times over the course of 2 runs. Contrasts of interest are the blood oxygen level-dependent (BOLD) response of CS+>tasteless solution and CS->tasteless solution deliveries. Parameter estimates for these contrasts are extracted and reported. A positive outcome reflects greater whole-brain BOLD response for the CS condition compared with a tasteless solution.

  5. Substrate Oxidation Response to Test Meals

    Time frame: 6-hour measurement

    Indirect calorimetry in a metabolic chamber will be used to assess substrate oxidation response to high-fat and high-carbohydrate test meals.

  6. Blood Glucose Response to Beverages

    Time frame: 2-hour measurement

    Blood glucose will be assessed at baseline and at set time points for 1 hour after consumption of intervention beverages in one exposure session.

  7. Blood Insulin Response to Beverages

    Time frame: 2-hour measurement

    Blood insulin will be assessed at baseline and at set time points for 2 hours after consumption of intervention beverages in an exposure session.

  8. Energy Expenditure in Response to Beverages

    Time frame: 1.5-hour measurement

    Indirect calorimetry will be used to determine energy expenditure at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session.

  9. Respiratory Exchange Ratio in Response to Beverages

    Time frame: 1.5-hour measurement

    Indirect calorimetry will be used to determine respiratory exchange ratio (RER) at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session. Areas under the curve for change in RER were calculated for each condition and presented as outcomes.

  10. Substrate Oxidation in Response to Beverages

    Time frame: 1.5-hour measurement

    Indirect calorimetry will be used to determine substrate oxidation at baseline (for 30 minutes) and for 1 hour after consumption of intervention beverages in an exposure session.

Sponsors and collaborators

Lead sponsor

Virginia Polytechnic Institute and State University

Other

Collaborators

  • National Center for Advancing Translational Sciences (NCATS)

Registry information

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Jan 21, 2022
Registry last updated
Sep 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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