Reduced-Calorie Diet for Obesity

(Lower CD Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Tennessee, Knoxville

Must not be taking: Weight loss medication

Disqualifiers: Heart condition, Major psychiatric diseases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a diet low in energy density (ED) might aid weight loss. Researchers aim to determine if consuming more low-ED foods, such as fruits and vegetables, reduces calorie intake and promotes fullness. Participants will either focus on eating many low-ED foods or combining them with fewer high-ED foods, like cookies and chips. This trial suits individuals with a body mass index (BMI) between 27 and 45 who are not currently in a weight loss program and can walk at least two blocks without stopping. As an unphased trial, it offers participants the chance to contribute to innovative research in dietary approaches to weight management.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications. However, if you are taking weight loss medication, you cannot participate in the trial.

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

Research has shown that eating fewer calories is generally safe for most people and can lead to significant weight loss. A typical plan involves consuming between 1,000 to 1,500 calories a day, which helps burn more calories than consumed.

Regarding safety, past studies have found these diets to be well-tolerated. In one study on a very low-calorie diet, participants did not report any serious side effects. Most people can follow the diet without major problems, although some might initially experience mild hunger or tiredness.

Overall, these diets have a strong track record for being safe and effective in helping people lose weight. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the reduced-calorie diet trial for obesity because it introduces a unique focus on energy density (ED) of foods as a guiding principle. Unlike other treatments that might focus solely on calorie counting or macronutrient balance, this approach encourages consuming foods with low energy density, such as fruits, vegetables, and broth-based soups, which can be more filling and nutritious. The COMBINATION arm further refines this by setting specific goals for the consumption of low-ED foods and limiting high-ED foods like crackers and cookies, aiming to foster healthier eating habits. This method could provide a more sustainable and intuitive way to manage weight, potentially offering a fresh perspective in obesity treatment strategies.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will compare two dietary strategies for weight loss. One group will follow the INCREASE condition, focusing on consuming at least 10 foods with an energy density (ED) of ≤ 1.0 kcal/g, such as fruits, vegetables, and broth-based soups. The COMBINATION group will have similar goals but will also limit high-ED foods and substitute them with low-ED options. Studies have shown that eating foods with fewer calories per bite can aid weight loss. Research indicates that consuming more foods like fruits, vegetables, and broth-based soups increases fullness, leading to reduced overall intake. One study found that increasing fruits and vegetables while reducing fatty foods is particularly effective for weight loss. Another study confirmed that diets with fewer calories per bite allow people to reduce calorie intake without decreasing food volume. Overall, these strategies help create a calorie deficit, which is necessary for losing weight. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a BMI of 27-45 kg/m2 who are not currently in a weight loss program or taking weight loss meds, haven't lost more than 5% body weight recently, don't have major heart conditions or psychiatric diseases, aren't pregnant or post-partum within six months, and can walk two blocks without stopping.

Inclusion Criteria

Body mass index (BMI) between 27 and 45 kg/m2

Exclusion Criteria

Report a heart condition, chest pain during periods of activity or rest, or loss of consciousness on the Physical Activity Readiness Questionnaire (PAR-Q)

I have a significant psychiatric condition or brain disorder.

Intend to move outside of the metropolitan area within the time frame of the investigation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a diet low in dietary energy density for weight loss

12 weeks

Weekly check-ins (virtual or in-person)

Follow-up

Participants are monitored for changes in weight, dietary intake, and physical activity

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Common components of intervention

Trial Overview

The study tests whether eating foods low in energy density (calories relative to food weight) helps with weight loss. It explores if it's better to increase low-energy-dense foods like fruits and vegetables or decrease high-energy-dense foods like fats.

How Is the Trial Designed?

Group I: COMBINATION Active Control 1 Intervention

This condition will be identical to the INCREASE condition, except it will also have a goal regarding the number of high-ED foods to consume and substituting low-ED foods for high-ED foods. Thus, this condition will have ED goals to consume at least 10 foods ≤ 1.0 kcal/g (i.e., fruits and vegetables, broth based soups, non-fat yogurts, some legumes, egg substitutes, some white fish, etc.) and no more than 2 foods ≥ 3.0 kcal/g (i.e., crackers, chips, cookies, hard cheeses, hot dogs, salad dressings, etc.) per day. Foods with an ED \>1.0 kcal/g but \< 3.0 kcal/g will be unlimited; however, lower ED foods will be strongly encouraged. Furthermore, additions to beverages (i.e., sugar, cream) will count toward the \> 3.0 kcal/g goal if the additions meet that ED criteria.

Group II: INCREASE Active Control 1 Intervention

This condition will be instructed to make food consumption decisions based solely upon the ED of a food. The goal of the ED condition will be to consume at least 10 foods ≤ 1.0 kcal/g (i.e., fruits and vegetables, broth based soups, non-fat yogurts, some legumes, egg substitutes, some white fish, etc.) per day.

Who Is Running the Clinical Trial?

The University of Tennessee, Knoxville

Lead Sponsor

Trials

93

Recruited

19,500+

Published Research Related to This Trial

A total of 4941 adverse event (AE) reports were identified for antiobesity medicines in Europe from 2007 to 2014, with over 90% classified as serious, including 159 deaths, highlighting significant safety concerns associated with these medications.

The most commonly reported serious AEs were cardiac (19%) and psychiatric disorders (18%), particularly linked to orlistat and rimonabant, indicating a need for ongoing safety monitoring despite the withdrawal of some products from the market.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. Aagaard, L., Hallgreen, CE., Hansen, EH.[2018]

Patients on a conventional 1200 kcal/d diet with behavior modification lose about 8.5 kg in 20 weeks and maintain two-thirds of this weight loss after one year.

Those on a medically supervised very-low-calorie diet (400 to 800 kcal/d) can lose around 20 kg in 12 to 16 weeks, but both diets show weight regain over time, which can be managed with ongoing care and participation in maintenance programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of obesity by moderate and severe caloric restriction. Results of clinical research trials. Wadden, TA.[2019]

Very low calorie diets (VLCD) can be effective for weight loss, but maintaining that weight loss requires follow-up support, including behavior modification and increased physical activity.

Safety concerns have arisen from the use of liquid protein supplements, which were linked to deaths; however, monitoring and using high-quality protein supplements have mitigated these risks, based on clinical experience with over 4000 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low calorie diets--history, safety and recent developments. Vertes, V.[2009]

A combination of dietary measures, including fat-reduced and carbohydrate-enhanced diets, can lead to significant weight loss in many obese patients, especially when paired with exercise and behavior modification.

If conservative methods fail after several years, adjunctive drug treatments or surgical options may be necessary for effective long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term weight reduction. Current therapy approaches in obesity]. Lichtenstein, S., Schulz, B., Hamann, A.[2015]

Medical therapy for obesity often fails in the long term, but successful weight loss programs are on the rise, emphasizing the importance of structured approaches.

An effective weight loss program should include caloric restriction, nutritional education, personalized exercise plans, behavioral modification, and ongoing support to help prevent weight regain and manage obesity as a chronic condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical management of obesity. Piziak, VK.[2005]

In a study of 44 patients with obesity, a Very Low Calorie Diet (VLCD) resulted in an average weight loss of 7 kg and a weight loss rate of 1.2 kg per week, indicating its effectiveness for weight management.

While 33% of participants reported mild side effects, such as constipation and dizziness, the majority (84%) adhered to the VLCD, suggesting that with proper support, adherence can be maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of Very Low Calory Diets in obese patients]. Sáez Belló, M., Segarra Villalba, C., Gras Colomer, E., et al.[2018]

A total of 25 anti-obesity medications were withdrawn between 1964 and 2009, primarily due to adverse reactions related to their effects on monoamine neurotransmitters, with 80% of withdrawals supported by case reports.

The most common reasons for withdrawal included psychiatric disturbances, cardiotoxicity, and drug dependence, raising concerns about the safety of using medications that target neurotransmitters for obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. Onakpoya, IJ., Heneghan, CJ., Aronson, JK.[2022]

In a study involving 53 overweight patients, those following a healthy eating diet lost an average of 6.0 kg over 12 weeks, which was significantly more than the 4.2 kg lost by those on an energy prescription diet.

Both dietary approaches resulted in clinically significant weight loss, but the healthy eating diet proved to be more effective, suggesting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic outpatient clinic: a pilot study. Taylor, F., Irons, L., Finn, P., et al.[2007]

In a study involving 53 overweight patients, those following a healthy eating diet lost an average of 6.0 kg over 12 weeks, which was significantly more than the 4.2 kg lost by those on an energy prescription diet.

Both dietary approaches resulted in clinically significant weight loss, but the healthy eating diet proved to be more effective, suggesting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic outpatient clinic - a pilot study. Taylor, FC., Irons, LJ., Finn, P., et al.[2019]

Lower-calorie diets consistently lead to greater short-term weight loss (less than 6 months) compared to higher-calorie diets, but this advantage tends to diminish over the long term (beyond 12 months).

While different macronutrient compositions (like low-carb vs. low-fat) may show short-term benefits, there are few significant long-term differences in weight loss, highlighting the importance of dietary adherence for sustained results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary interventions for obesity: clinical and mechanistic findings. Chao, AM., Quigley, KM., Wadden, TA.[2022]

Current guidelines recommend a comprehensive treatment for obesity that includes diet, exercise, and behavior therapy, emphasizing the importance of cognitive change for better long-term results.

Cognitive behavioral therapy combined with the Mediterranean diet has shown effectiveness in promoting weight loss and improving health markers, making it a practical approach for managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional and behavioral modification therapies of obesity: facts and fiction. Vranešić Bender, D., Krznarić, Z.[2018]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

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