Carbohydrate Consumption for Understanding Food Reward Mechanisms

(CARB Trial)

Overseen By Alexandra G DiFeliceantonio, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Must not be taking: Antiglycemics, Thyroid, Sleep medications

Disqualifiers: Nicotine, Alcohol dependence, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how carbohydrates affect the brain's reward system and influence food choices. By testing different carbohydrate drinks, researchers aim to understand how the brain responds to the energy content in foods and why processed foods are so appealing. The trial involves three groups receiving different types of carbohydrate drinks to observe how quickly or slowly the energy reaches the brain. Individuals with a BMI between 18.5 and 30, who are not on special diets and live near Roanoke, may be suitable for this study.

As an unphased trial, participants can contribute to groundbreaking research on diet and brain health.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to influence study measures, such as antiglycemic agents (medications that lower blood sugar), thyroid medications, and sleep medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments under study, including CS- Beverage, CS+Fast, and CS+Slow, are generally well-tolerated. For CS- Beverage, studies have examined the effects of carbohydrates and found mild side effects. However, excessive sugar consumption can affect the brain's reward system, making sugary foods more appealing.

For CS+Fast, no direct evidence of safety issues exists, but research indicates that ultra-processed foods, similar to fast-releasing carbohydrates, can be linked to health problems. Positively, some evidence suggests carbohydrates can support gut health.

The CS+Slow treatment involves slow-release carbohydrates, which appear beneficial. They release sugar into the blood more gradually, helping manage insulin levels and support gut health, suggesting they are safe to consume.

Overall, these treatments are being studied for their effects on food reward experiences, and current data suggest they are safe for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover how different timing and methods of carbohydrate consumption can influence food reward mechanisms in our brains. Unlike standard dietary approaches that generally focus on the nutritional value or caloric intake, this study explores how the speed of carbohydrate ingestion—either rapidly with CS+Fast or more slowly with CS+Slow—affects our brain's reward system. By understanding these mechanisms, scientists hope to develop new strategies for managing eating behaviors and potentially addressing issues like overeating or obesity.

What evidence suggests that this trial's treatments could be effective for understanding food reward mechanisms?

Research has shown that the pleasure derived from eating, known as food reward, is linked to the calorie content of foods. This trial will explore different carbohydrate consumption patterns. Participants in the "CS-First" arm will receive a conditional stimulus beverage. Those in the "CS+Fast First" arm will consume fast-acting carbohydrates, which studies have found can enhance brain and behavior responses related to food enjoyment. Meanwhile, participants in the "CS+Slow First" arm will receive slower-acting carbohydrates. Evidence suggests that these slower-acting carbohydrates provide a steadier energy release and might influence food preferences differently. The speed at which these carbohydrates affect the body and brain could impact eating habits and food choices. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking adults with a BMI of 18.5-30, living near Roanoke or able to visit the Fralin Biomedical Research Institute. It's not for those who are pregnant, have high blood sugar levels (Hemoglobin A1C >5.7%), work night shifts, had weight loss surgery, use inhaled nicotine, have metal implants that affect MRI scans, or have certain medical conditions like diabetes.

Inclusion Criteria

You are located in or able to travel to Roanoke for sessions at the Fralin Biomedical Research Institute.

Your body mass index (BMI) is between 18.5 and 30, which means you have a healthy weight for your height.

You are not expecting or planning a pregnancy during the study.

Exclusion Criteria

You have had a problem with alcohol addiction in the past.

I have been diagnosed with diabetes or thyroid issues.

I am currently taking medication that could affect the study's results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intervention beverages and undergo various assessments including energy expenditure, substrate oxidation, and blood glucose response.

5 weeks

Weekly visits for assessments

Follow-up

Participants are monitored for changes in preference and physiological responses after the intervention.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CS- Beverage
• CS+Fast
• CS+Slow

Trial Overview The study examines how different types of carbohydrate-rich beverages influence brain activity and food preferences. Participants will try three kinds: a control beverage (CS-), one that releases carbs slowly (CS+Slow), and another that releases them quickly (CS+Fast). The goal is to see if the speed at which carbs hit the system affects their rewarding properties.

How Is the Trial Designed?

Group I: CS- First Experimental Treatment 3 Interventions

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

Group II: CS+Slow First Experimental Treatment 3 Interventions

Participants who receive the CS+Slow First

Group III: CS+Fast First Experimental Treatment 3 Interventions

Participants who receive the CS+Fast First

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Published Research Related to This Trial

Glucose rapidly increases in the nucleus accumbens of rats after intravenous delivery, showing a strong dose-dependent response, while fructose only produces a minimal effect at high doses.

Rats demonstrate a significant preference for glucose over fructose, which develops over time with repeated exposure, suggesting that glucose's direct action in the brain plays a crucial role in its consumption and preference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain. Wakabayashi, KT., Spekterman, L., Kiyatkin, EA.[2023]

Intraperitoneal injections of glucose significantly suppressed sham feeding by about 42%, indicating that postprandial glucose levels can reduce the motivation to eat based on taste, especially when glucose is administered alongside taste stimulation.

The effectiveness of glucose in inhibiting eating was enhanced when the gastric cannula was closed, suggesting that glucose works together with other signals from the stomach to signal fullness, rather than causing discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postabsorptive glucose decreases excitatory effects of taste on ingestion. Bédard, M., Weingarten, HP.[2017]

In a study involving 68 adults with type 2 diabetes, empagliflozin (25 mg daily) combined with dietary energy restriction led to the most significant weight loss of 5.74 kg over 24 weeks, compared to other groups.

Despite the weight loss, the changes in appetite-regulating peptides like PYY and GLP-1 did not show significant differences between the treatment groups and the placebo, suggesting that these peptides may not explain the observed weight loss with empagliflozin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of empagliflozin, dietary energy restriction, or both on appetite-regulatory gut peptides in individuals with type 2 diabetes and overweight or obesity: The SEESAW randomized, double-blind, placebo-controlled trial. Sargeant, JA., King, JA., Yates, T., et al.[2022]

In a study involving 18 healthy individuals, dapagliflozin did not significantly affect overall energy intake or appetite ratings compared to a placebo, suggesting it may not influence eating behavior in this population.

Although not statistically significant, dapagliflozin trended towards increasing the desire for salty and sweet foods, which may relate to its effects on sodium and glucose excretion, indicating potential areas for further research, especially in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Dapagliflozin Affect Energy Intake and Appetite? A Randomized, Controlled Exploratory Study in Healthy Subjects. Bertran, E., Berlie, HD., Nixon, A., et al.[2021]

The novel GLP-1/Dexa conjugate significantly reduced food motivation and intake in obese mice, showing a sustained effect for up to 20 hours, which is longer than the 4-hour effect seen with GLP-1 alone.

Importantly, treatment with GLP-1/Dexa led to weight loss without negatively impacting mood or memory, suggesting it could be a safe and effective strategy for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1/dexamethasone inhibits food reward without inducing mood and memory deficits in mice. Décarie-Spain, L., Fisette, A., Zhu, Z., et al.[2019]

In a study involving 18 subjects with type 2 diabetes, liraglutide significantly reduced appetite and energy intake compared to placebo, with participants reporting lower hunger ratings and higher fullness after treatment.

The estimated energy intake was 18% lower with liraglutide, suggesting that its appetite-suppressing effects may play a key role in promoting weight loss in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The once-daily human GLP-1 analogue liraglutide impacts appetite and energy intake in patients with type 2 diabetes after short-term treatment. Flint, A., Kapitza, C., Zdravkovic, M.[2015]

Intraperitoneal administration of gut hormones CCK, GLP-1, and PYY3-36 significantly reduced the consumption of a highly palatable sucrose solution in mice, indicating their potential to suppress hedonic-driven sugar intake.

The doses of these hormones did not cause conditioned taste aversion, suggesting that their effects on reducing sugar consumption are not associated with unpleasant side effects, making them a promising avenue for controlling excessive sugar intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of anorexic gut peptide hormones impairs hedonic-driven sucrose consumption in mice. Yamaguchi, E., Yasoshima, Y., Shimura, T.[2018]

Mice lacking the mGlu5 receptor weighed less than control mice despite similar food intake, indicating that mGlu5 plays a role in body weight regulation independent of food consumption.

The mGlu5 antagonist MTEP effectively reduced food intake and prevented weight gain in diet-induced obese rats, suggesting that targeting mGlu5 could be a potential strategy for managing obesity and enhancing energy expenditure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. Bradbury, MJ., Campbell, U., Giracello, D., et al.[2014]

In a study involving diet-induced obese mice treated with the mGluR5 negative allosteric modulator VU0409106 for 14 days, significant reductions in food intake, body weight, and inflammation in adipose tissue were observed, suggesting its potential as an obesity treatment.

VU0409106 also showed effectiveness in reducing binge-like eating behaviors, indicating that targeting mGluR5 could be beneficial not only for obesity but also for related eating disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior. Oliveira, TPD., Gonçalves, BDC., Oliveira, BS., et al.[2023]

Intracerebroventricular administration of metformin significantly reduced food intake in rats by blocking the appetite-stimulating effects of the peptide ghrelin, demonstrating a dose-dependent response.

Metformin's mechanism involves the inhibition of ghrelin-induced activation of hypothalamic AMPK signaling pathways and restoration of mTOR activity, which are crucial for regulating appetite.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebroventricular administration of metformin inhibits ghrelin-induced Hypothalamic AMP-kinase signalling and food intake. Stevanovic, D., Janjetovic, K., Misirkic, M., et al.[2013]

In a 24-week study involving 15 overweight/obese participants with type 1 diabetes, adding liraglutide to their insulin therapy led to a significant reduction in total food intake and fat consumption, while increasing carbohydrate intake.

Participants also experienced decreased appetite sensations, including reduced hunger and desire to eat, and an increased feeling of fullness after meals, indicating improved eating behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of liraglutide on food consumption, appetite sensations and eating behaviours in overweight people with type 1 diabetes. Dubé, MC., D'Amours, M., Weisnagel, SJ.[2021]

In a study of 13 obese participants with varying degrees of insulin resistance, those with higher insulin resistance showed a stronger preference for sugar-sweetened yogurts over monkfruit-sweetened options, indicating that insulin resistance may increase the desire for sugary foods.

The preference for sugar-sweetened yogurt was significantly correlated with measures of insulin resistance and blood glucose levels, suggesting that managing insulin resistance could be key in helping individuals make healthier dietary choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin Resistance and Glycated Hemoglobin in Obesity Are Associated With Preference for Sugar-Sweetened Yogurt: A Pilot Study. Epstein, LH., Biondolillo, MJ., Rizwan, A., et al.[2023]

Mild hypoglycemia increases the desire for high-calorie foods by activating specific brain regions, while normal glucose levels reduce interest in food stimuli, highlighting the role of glucose in food motivation.

Obese individuals show a lack of the normal brain response to higher glucose levels, suggesting that they may lose the ability to regulate their desire for high-calorie foods, which could contribute to overeating.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. Page, KA., Seo, D., Belfort-DeAguiar, R., et al.[2023]

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Potential Role of Intermittent Fasting on Food Reward‐ ... IF improves eating behavior by modulating central mechanisms such as food reward, reducing neuroinflammation, and restoring both homeostatic ...