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

60 Participants Needed

Trial Summary

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.

What data supports the effectiveness of a reduced-calorie diet treatment for obesity?

Research shows that lower-calorie diets can lead to significant short-term weight loss, and when combined with other treatments like medication, they can help maintain weight loss over a longer period. ^{1 2 3 4 5}

Is a reduced-calorie diet safe for treating obesity?

Very low-calorie diets (VLCDs) have been used for about ten years and are generally safe when patients are properly selected, given high-quality protein supplements, and monitored by healthcare professionals. However, there have been concerns about safety, especially when liquid protein diets were sold over the counter, which were linked to deaths. Proper monitoring and support are crucial to ensure safety. ^{6 7 8 9 10}

How does the reduced-calorie diet treatment for obesity differ from other treatments?

The reduced-calorie diet treatment for obesity is unique because it focuses on significant caloric restriction, often under medical supervision, which can lead to rapid weight loss. Unlike other treatments, it emphasizes a very-low-calorie diet (400 to 800 kcal/d) combined with behavior modification to help maintain weight loss over time. ^{11 12 13 14 15}

What is the purpose of this trial?

For weight loss to occur, energy intake needs to be reduced to incur an energy deficit. One dietary strategy that may facilitate reducing energy intake and enhancing weight loss is consuming a diet low in dietary energy density (ED). The ED of a given food, defined as the ratio of energy of the food to the weight of the food (kcal/g), is largely determined by water content, but is also affected by fat and fiber. Although the 2010 Dietary Guidelines encourage an eating pattern low in energy density (ED) to manage weight, it is currently not known what the best strategy is for reducing ED in the diet. Eating a greater number of foods low in ED or reducing the number of foods high in ED may reduce overall dietary ED. As ED is believed to reduce intake by allowing a greater weight of food relative to total energy consumed assisting with enhancing feelings of fullness, it is anticipated that either increasing consumption of low-ED foods in the diet alone or combining an increase in consumption of low-ED foods with a decrease in consumption of high-ED foods may be the best strategies for reducing overall dietary ED for weight loss.

Eligibility Criteria

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 am in a weight loss program or taking medication for it, or I've lost more than 5% of my body weight in the last 6 months.

I have a significant psychiatric condition or brain disorder.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Review of 3-year outcomes of a very-low-energy diet-based outpatient obesity treatment programme. [2016]

2. England pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic outpatient clinic: a pilot study. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic outpatient clinic - a pilot study. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Dietary interventions for obesity: clinical and mechanistic findings. [2022]

5. England pubmed.ncbi.nlm.nih.gov

What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions. [2018]

6. Spain pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of Very Low Calory Diets in obese patients]. [2018]

7. Netherlands 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Post-marketing withdrawal of anti-obesity medicinal products because of adverse drug reactions: a systematic review. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Serious adverse events reported for antiobesity medicines: postmarketing experiences from the EU adverse event reporting system EudraVigilance. [2018]

11. Germany pubmed.ncbi.nlm.nih.gov

[Long-term weight reduction. Current therapy approaches in obesity]. [2015]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Nutritional and behavioral modification therapies of obesity: facts and fiction. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Medical management of obesity. [2005]

14. United States pubmed.ncbi.nlm.nih.gov

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

15. United States pubmed.ncbi.nlm.nih.gov

Obesity. Part II--Treatment. [2018]