Calorie Reduction for Obesity

(CARE Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Antipsychotics, MAO inhibitors, Corticosteroids, Chemotherapy

Disqualifiers: Hypertension, Cancer, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two weight loss programs to determine which is more effective: consistent calorie reduction or varied calorie reduction. One group will maintain a steady calorie cut, while the other will alternate between eating less and eating even less. It suits adults who have lived with obesity for some time and are willing to try a structured eating plan. Participants should not have recently experienced significant weight loss or have serious health issues that could impact their ability to participate safely. As an unphased trial, this study allows participants to contribute to innovative research in weight management strategies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including antipsychotic agents, monoamine oxidase inhibitors, systemic corticosteroids, antibiotics for HIV or TB, chemotherapeutic drugs, and prescription weight loss medications.

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

Research has shown that reducing calorie intake can safely aid in weight loss. Studies have found that consuming fewer calories helps people lose weight without causing serious health issues. One study discovered that strict calorie-cutting programs led to significant weight loss in young people with obesity. Importantly, most participants tolerated these programs well, reporting no major negative effects.

Calorie reduction works by lowering the body's energy use, and people typically adjust to this change without harm. Some might experience slight hunger or reduced energy, but these side effects are usually manageable. Overall, calorie reduction is considered safe for most people when done with guidance. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the calorie reduction strategies being tested for obesity because they offer a fresh approach to weight loss. Unlike traditional methods that often prescribe a single, consistent calorie reduction, the "Variable Energy Reduction" method introduces alternating levels of calorie reduction. This dynamic approach may help sustain weight loss by potentially preventing the body's metabolism from adapting to a constant calorie intake. On the other hand, the "Fixed Energy Reduction" approach provides a straightforward moderate reduction, which could be easier for some participants to maintain consistently. By comparing these two methods, researchers hope to uncover more effective and sustainable strategies for managing obesity.

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

This trial will compare two approaches to calorie reduction for weight loss. Research has shown that varying daily calorie intake, known as variable energy reduction, can aid in weight loss. Participants in the variable energy reduction arm will alternate between two levels of calorie reduction. One study found that a diet of approximately 1,365 calories per day led to weight loss in obese participants. This approach may better manage energy levels, potentially making it more effective for weight loss. Another study supports that various methods of calorie reduction, including this one, can help reduce obesity-related health issues. The body might respond better to these changing calorie levels, making them a promising option for weight loss. Meanwhile, participants in the fixed energy reduction arm will maintain a consistent moderate calorie reduction until achieving their weight loss goal. ^{6 7 8 9 10}

Who Is on the Research Team?

Gareth R Dutton, PhD

Principal Investigator

University of Alabama at Birmingham, Department of Medicine, Division of Preventive Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 21-75 with obesity (BMI of 30-50). It's not suitable for those with certain chronic diseases, uncontrolled high blood pressure, recent heart attacks or strokes, major psychiatric disorders, or a history of significant weight loss or bariatric surgery. Pregnant women and those planning pregnancy are excluded.

Inclusion Criteria

I am between 21 and 75 years old.

Body mass index (BMI) 30-50 kg/m2

Exclusion Criteria

I have had weight loss surgery in the past.

My blood pressure is not higher than 160/100 mm Hg.

I have not had unstable chest pain in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow either a fixed or variable calorie reduction plan to achieve weight loss

18 months

Regular visits for monitoring and support

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Energy Reduction

Trial Overview The CARE Trial aims to compare two diet programs focusing on different methods of calorie reduction to see which one is more effective at helping participants lose weight. Participants will be randomly assigned to follow either a fixed calorie reduction plan or a varied calorie reduction plan.

How Is the Trial Designed?

Group I: Variable Energy (or Calorie) Reduction Experimental Treatment 1 Intervention

Participants randomly assigned to this arm will be instructed to alternate between two levels of calorie reduction. One level will be a small amount of calorie reduction, while the other will be a more significant amount of calorie reduction. At the instruction of the research team, participants will periodically alternate back and forth between these two goals until their weight loss goal is achieved.

Group II: Fixed Energy (or Calorie) Reduction Active Control 1 Intervention

Participants randomly assigned to this arm will be instructed to reduce their food intake by a moderate amount and stay at this level of moderate reduction until their weight loss goal is achieved.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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]

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]

Weight loss supplements in the U.S. are not regulated as drugs by the FDA, which means they undergo minimal testing for safety and efficacy, leading to potential risks for consumers.

Healthcare providers need to be aware of the lack of evidence supporting the effectiveness of these supplements and advocate for better regulatory oversight to protect consumers from unproven and possibly harmful products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society's Clinical Committee. Kidambi, S., Batsis, JA., Donahoo, WT., et al.[2021]

Low-calorie diets, particularly those with a 600-kcal deficit, can lead to significant weight loss, averaging around 10 kg, especially in individuals with higher initial body weight.

Despite the effectiveness of low-calorie diets, the best methods for implementing these diets remain uncertain, as few randomized trials exist and various adjunct therapies complicate the evaluation of different dietary approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-calorie diets and sustained weight loss. Finer, N.[2007]

Minor weight loss of 5-10% can significantly reduce health risks associated with obesity, but very low-calorie diets alone are not effective for long-term weight management.

Bariatric surgery is a safe and effective option for morbidly obese patients, especially those with additional cardiovascular risk factors, with adjustable gastric banding being a viable alternative to other surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Overweight. III. Therapeutic strategies for weight reduction]. Pijl, H., Meinders, AE.[2006]

A study involving over 28,000 patients found that orlistat and sibutramine have different safety profiles, with orlistat primarily causing gastrointestinal issues like diarrhea, while sibutramine was associated with central nervous system effects and hypertension.

The findings from prescription-event monitoring (PEM) were consistent with published case reports, confirming that the adverse events linked to these medications align with their distinct mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. Perrio, MJ., Wilton, LV., Shakir, SA.[2021]

In a study of 46 very obese individuals (11 inpatients and 35 outpatients), it was found that their caloric intake was directly related to their level of obesity, with both groups consuming high-calorie density foods and engaging in occasional binge eating.

By replacing high-calorie density foods with lower-calorie options, participants could potentially reduce their caloric intake by 20%, which could significantly aid in weight loss efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food intake of very obese persons: quantitative and qualitative aspects. Strain, GW., Hershcopf, RJ., Zumoff, B.[2007]

Citations

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Calorie Shifting Diet Versus Calorie Restriction Diet Four weeks of CSD caused weight loss in obese subjects by limiting the energy intake to 1,365 calorie per day. CSD helped them approach a significant energy ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5568065/

Body Weight Regulation and the Effects of Diet Composition Reductions in energy intake lead to decreased energy expenditure to a degree that is often greater than expected based on changes in body composition or the ...

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CARE Trial: Comparing Different Levels of Calorie Reducti... This research study will compare two weight loss programs that provide different recommendations for how to reduce your energy (or calorie) ...

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Comparing caloric restriction regimens for effective weight ... Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health ...

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The energy balance model of obesity: beyond calories in, ... We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the ...

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Impact of calorie restriction on energy metabolism in humans Calorie restriction induces a reduction in energy expenditure that is larger than the loss of metabolic mass, ie fat-free mass and fat mass.

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Caloric Restriction in Humans: Impact on Physiological ... This study of nature of caloric restriction resulted in ∼15% weight loss (B), in changes in energy expenditure and physical activity (C), and many ...

8. mdpi.com mdpi.com/2072-6643/16/18/3125

Efficacy, Safety and Acceptability of a Very-Low-Energy ... Our 2019 meta-analysis of 20 studies found VLED programs led to a mean weight loss of 10.1 kg in children and adolescents with obesity following ...

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Obesity: Prevalence, causes, consequences, management ... Obesity has reached epidemic proportions worldwide, with over 1 billion people classified as obese in 2022, representing 13% of the global population.

10. jomes.org jomes.org/journal/view.html?doi=10.7570/jomes.2018.27.4.203

Dynamic Energy Balance and Obesity Prevention Dynamic energy balance can give clinicians important answers for why obesity is so resistant to control.