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The Impact of the Physiological Response to Sugar on Brain Activity and Behavior

The Impact of the Physiological Response to Sugar on Brain Activity and Behavior

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT06015490
Enrollment
7
Registered
2023-08-29
Start date
2023-09-01
Completion date
2024-07-22
Last updated
2025-09-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Food Preferences, Appetitive Behavior

Brief summary

The goal of this pilot study is to test the feasibility of assessing how biological factors and chemical properties of sugars may influence metabolism and food reward in humans. The main questions it aims to answer are: • Can differences in appetitive responses and neural activations to sucrose (table sugar) and its chemical components (glucose and fructose) be measured and quantified? This study is a crossover design, meaning every participant will complete every condition. Participants will consume beverages containing sucrose, glucose, or fructose, which are each novelly flavored, 6 times within a week. During one of the consumption times, energy expenditure, carbohydrate oxidation, and blood glucose will be measured in the lab before and for 2 hours after consumption. After participants have consumed each condition, they will undergo a tasting task in the MRI scanner, neural responses to receipt of the beverages are measured.

Detailed description

Prior studies in humans indicate that while energy expenditure response is similar after consumption of equal amounts of fructose, glucose, and sucrose (a dimer of glucose + fructose), carbohydrate oxidation and blood glucose responses differ. Elevated carbohydrate oxidation responses appear to be driven by the presence of fructose, and elevated blood glucose responses appear to be driven by the presence of glucose. Prior work also suggests that post-ingestive signals of glucose availability, measure specifically as blood glucose levels, intestinal glucose transporter activity, and carbohydrate oxidation rate, are all associated with elevated brain response to calorie-predictive flavor cues and reward learning of these flavor cues. However, in animal models, glucose has been shown to repeatedly and reliably condition these calorie-predictive learning responses, but fructose does not. Human work has indicated that oxidation of glucose is critical for these responses. Thus, it is unclear what roles fructose and glucose each play in conditioning reward responses and flavor-calorie learning. We hypothesize that fructose plays a synergistic role in enhancing flavor-calorie learning without itself conditioning the reward response.

Interventions

OTHERSucrose drink

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 measurements inside a metabolic chamber over a 2-hour period. The other 5 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.

Participants will consume flavored beverage solutions containing 110 calories of glucose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 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.

Participants will consume flavored beverage solutions containing 110 calories of fructose in 6 exposure sessions within 1 week. One exposure session will include pre- and post-consumption blood draws and indirect calorimetry measurements inside a metabolic chamber over a 2-hour period. The other 5 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.

Sponsors

Virginia Polytechnic Institute and State University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)

Eligibility

Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

1. BMI between 18.5-25 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 (FBRI) at Virginia Tech Carilion 4. Weigh at least 110 lbs

Exclusion criteria

1. Current inhaled nicotine use 2. History of alcohol dependence. 3. Current or past diagnosis of cardiometabolic disease or problems, including diabetes, endocrine, heart, or thyroid problems, that may influence study outcomes 4. Hemoglobin A1C \>5.7% 5. Taking medications known to influence study measures (including attention-deficit/hyperactivity disorder (ADHD), allergy, antidepressant, antipsychotic, anxiolytic, birth control, blood pressure, blood glucose, cholesterol, thyroid, sleep, or weight loss medications) 6. Active medical or neurologic disorder, including cardiometabolic conditions or gastrointestinal conditions that may influence study outcomes 7. Recent change in body weight (gain or loss of \> 5 lbs within the past 3 months) 8. Current shift work (typical pattern of work/activity overnight) 9. Previous weight loss surgery 10. 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.) 11. Allergy to any food or ingredient included in the study diets, meals, or beverages 12. Currently pregnant or planning to become pregnant during study participation 13. Claustrophobia 14. 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.) 15. Contraindications for bioelectrical impedance analysis, specifically implanted devices 16. Use of substances (or combinations of substances) in doses and frequencies that could influence neural outcomes of study.

Design outcomes

Primary

MeasureTime frameDescription
Change in Preference- Subjective Liking Ratings for Each Beverage on a ScaleImmediately after informed consent and in the post-test session approximately 5 weeks laterSubjective 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.

Secondary

MeasureTime frameDescription
Post-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the OutcomeAt the end of study; approximately 5 weeks after first sessionAd 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.
Post-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated BeverageAt the end of study; approximately 5 weeks after first sessionForced 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.
Post-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a ScaleAt the end of study; approximately 5 weeks after first sessionSubjective ratings of liking 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.
Blood Glucose Response to BeveragesEach week for 3 weeks during the studyBlood glucose will be assessed at baseline and at set time points for 2 hours after consumption of intervention beverages (baseline, 5-, 20-, 40-, 60-, 90-, and 120-minutes after drink consumption)in one exposure session. Area under the curve is calculated using these time points and reported as the outcome measure.
Energy Expenditure in Response to BeveragesEach week for 3 weeks during the studyIndirect calorimetry will be used to determine energy expenditure at baseline and for 120 minutes after consumption of condition beverages in an exposure session. Area under the curve is calculated as a change from baseline energy expenditure using minute-by-minute resolution across 120 minutes and reported as the outcome measure.
Blood Oxygen Level-dependent (BOLD) Response to BeveragesAt the end of study; approximately 5 weeks after first sessionIn 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. Participants receive the glucose, sucrose, fructose, and tasteless (control) solutions 18 times each over the course of 2 runs. Contrasts of interest are the blood oxygen level-dependent (BOLD) response of glucose+\>tasteless solution, sucrose\>tasteless solution, and fructose\>tasteless deliveries. Parameter estimates for these contrasts are extracted and reported. A positive outcome reflects greater whole-brain BOLD response for the sugar condition compared with a tasteless solution.

Countries

United States

Participant flow

Participants by arm

ArmCount
Sucrose, Then Glucose, Then Fructose
Participants will consume a 110 kcal sucrose drink 6 times during 1 week. Then, they will consume a 110 kcal glucose drink 6 times during 1 week, and then, a 110 kcal fructose drink 6 times during 1 week.
1
Sucrose, Then Fructose, Then Glucose
Participants will consume a 110 kcal sucrose drink 6 times during 1 week. Then, they will consume a 110 kcal fructose drink 6 times during 1 week, and then, a 110 kcal glucose drink 6 times during 1 week.
2
Glucose, Then Fructose, Then Sucrose
Participants will consume a 110 kcal glucose drink 6 times during 1 week. Then, they will consume a 110 kcal fructose drink 6 times during 1 week, and then, a 110 kcal sucrose drink 6 times during 1 week.
0
Glucose, Then Sucrose, Then Fructose
Participants will consume a 110 kcal glucose drink 6 times during 1 week. Then, they will consume a 110 kcal sucrose drink 6 times during 1 week, and then, a 110 kcal fructose drink 6 times during 1 week.
1
Fructose, Then Glucose, Then Sucrose
Participants will consume a 110 kcal fructose drink 6 times during 1 week. Then, they will consume a 110 kcal glucose drink 6 times during 1 week, and then, a 110 kcal sucrose drink 6 times during 1 week.
1
Fructose, Then Sucrose, Then Glucose
Participants will consume a 110 kcal fructose drink 6 times during 1 week. Then, they will consume a 110 kcal sucrose drink 6 times during 1 week, and then, a 110 kcal glucose drink 6 times during 1 week.
2
Total7

Baseline characteristics

CharacteristicSucrose, Then Glucose, Then FructoseTotalFructose, Then Sucrose, Then GlucoseFructose, Then Glucose, Then SucroseGlucose, Then Sucrose, Then FructoseSucrose, Then Fructose, Then Glucose
Age, Continuous25 years
STANDARD_DEVIATION 0
28.4 years
STANDARD_DEVIATION 6.9
22 years
STANDARD_DEVIATION 1.4
31 years
STANDARD_DEVIATION 0
42 years
STANDARD_DEVIATION 0
28.5 years
STANDARD_DEVIATION 0.7
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants7 Participants2 Participants1 Participants1 Participants2 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
1 Participants2 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Black or African American
0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
0 Participants4 Participants2 Participants1 Participants0 Participants1 Participants
Region of Enrollment
United States
1 participants7 participants2 participants1 participants1 participants2 participants
Sex: Female, Male
Female
0 Participants2 Participants1 Participants0 Participants0 Participants1 Participants
Sex: Female, Male
Male
1 Participants5 Participants1 Participants1 Participants1 Participants1 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 60 / 70 / 6
other
Total, other adverse events
0 / 60 / 70 / 6
serious
Total, serious adverse events
0 / 60 / 70 / 6

Outcome results

Primary

Change in Preference- Subjective Liking Ratings for Each Beverage on a Scale

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.

Time frame: Immediately after informed consent and in the post-test session approximately 5 weeks later

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkChange in Preference- Subjective Liking Ratings for Each Beverage on a Scale-12.8 units on a scaleStandard Deviation 26.3
Fructose DrinkChange in Preference- Subjective Liking Ratings for Each Beverage on a Scale-12.0 units on a scaleStandard Deviation 26.2
Sucrose DrinkChange in Preference- Subjective Liking Ratings for Each Beverage on a Scale-12.6 units on a scaleStandard Deviation 26.3
Secondary

Blood Glucose Response to Beverages

Blood glucose will be assessed at baseline and at set time points for 2 hours after consumption of intervention beverages (baseline, 5-, 20-, 40-, 60-, 90-, and 120-minutes after drink consumption)in one exposure session. Area under the curve is calculated using these time points and reported as the outcome measure.

Time frame: Each week for 3 weeks during the study

Population: One participant withdrew from the study prior to the glucose and sucrose drink sessions but completed the fructose drink session.

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkBlood Glucose Response to Beverages16821.25 mg/dl*minStandard Deviation 4861.348755
Fructose DrinkBlood Glucose Response to Beverages11484.58334 mg/dl*minStandard Deviation 1468.61789
Sucrose DrinkBlood Glucose Response to Beverages13760.66666 mg/dl*minStandard Deviation 3813.485448
Secondary

Blood Oxygen Level-dependent (BOLD) Response to Beverages

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. Participants receive the glucose, sucrose, fructose, and tasteless (control) solutions 18 times each over the course of 2 runs. Contrasts of interest are the blood oxygen level-dependent (BOLD) response of glucose+\>tasteless solution, sucrose\>tasteless solution, and fructose\>tasteless deliveries. Parameter estimates for these contrasts are extracted and reported. A positive outcome reflects greater whole-brain BOLD response for the sugar condition compared with a tasteless solution.

Time frame: At the end of study; approximately 5 weeks after first session

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkBlood Oxygen Level-dependent (BOLD) Response to Beverages0.005 arbitrary unitsStandard Deviation 0.085
Fructose DrinkBlood Oxygen Level-dependent (BOLD) Response to Beverages0.109 arbitrary unitsStandard Deviation 0.186
Sucrose DrinkBlood Oxygen Level-dependent (BOLD) Response to Beverages0.050 arbitrary unitsStandard Deviation 0.21
Secondary

Energy Expenditure in Response to Beverages

Indirect calorimetry will be used to determine energy expenditure at baseline and for 120 minutes after consumption of condition beverages in an exposure session. Area under the curve is calculated as a change from baseline energy expenditure using minute-by-minute resolution across 120 minutes and reported as the outcome measure.

Time frame: Each week for 3 weeks during the study

Population: Technical challenges with equipment and data collection resulted in lower sample size for analysis for this outcome.

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkEnergy Expenditure in Response to Beverages-0.89 kcal/min*minStandard Deviation 6.63
Fructose DrinkEnergy Expenditure in Response to Beverages0.940 kcal/min*minStandard Deviation 6.14
Sucrose DrinkEnergy Expenditure in Response to Beverages1.89 kcal/min*minStandard Deviation 3.86
Secondary

Post-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a Scale

Subjective ratings of liking 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.

Time frame: At the end of study; approximately 5 weeks after first session

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkPost-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a Scale42 units on a scaleStandard Deviation 12.7
Fructose DrinkPost-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a Scale54.8 units on a scaleStandard Deviation 12.5
Sucrose DrinkPost-Test Measure of Preference- Subjective Wanting Ratings for Each Beverage on a Scale46.9 units on a scaleStandard Deviation 14.5
Secondary

Post-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the Outcome

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.

Time frame: At the end of study; approximately 5 weeks after first session

ArmMeasureValue (MEAN)Dispersion
Glucose DrinkPost-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the Outcome67.8 ml consumedStandard Deviation 98.1
Fructose DrinkPost-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the Outcome66.0 ml consumedStandard Deviation 99.1
Sucrose DrinkPost-Test Measure of Preference - Wanting (ad Libitum Intake): The Amount Consumed of Each Beverage is Reported as the Outcome66.3 ml consumedStandard Deviation 98.5
Secondary

Post-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated Beverage

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.

Time frame: At the end of study; approximately 5 weeks after first session

Population: In the post-test session, participants are asked to choose among the Glucose, Sucrose, and Fructose Drinks which they would like to take home in a forced choice test. Participants are only allowed to choose one of the three conditions.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Glucose DrinkPost-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated Beverage1 Participants
Fructose DrinkPost-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated Beverage3 Participants
Sucrose DrinkPost-Test Measure of Preference- Wanting (Forced Choice): Number of Participants Who Chose Each Indicated Beverage2 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026