Low Calorie Diet for Obesity

(SEV Trial)

Recruiting at 1 trial location

Overseen By Kyle Timmons

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Affect study outcomes

Disqualifiers: Diabetes, Liver disease, Excessive alcohol, others

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

Compensation: Varies

Number of Visits: 1

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why some individuals with obesity develop conditions like type 2 diabetes and heart disease, while others do not. Researchers will study how small particles from these individuals affect metabolic function in cells and mice. The trial will include participants with metabolically unhealthy obesity, who will follow a low-calorie diet to observe its effects. It is well-suited for individuals with obesity who have high blood sugar and fat levels and experience insulin resistance. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance the understanding and treatment of obesity-related conditions.

Will I have to stop taking my current medications?

The trial requires that you do not take medications that could affect the study outcome measures, so you may need to stop certain medications. It's best to discuss your specific medications with the study team.

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

Research shows that low-calorie diets can be a safe option for people with unhealthy obesity. Studies have found that most individuals can follow these diets without major problems. For example, one program that included a calorie-restricted diet reported positive results after a year, with participants managing the diet well.

Some individuals might experience mild side effects when starting a low-calorie diet, such as tiredness or hunger. However, these diets usually don't cause serious issues.

Prospective clinical trial participants should consult a healthcare provider to determine if this type of treatment is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the low-calorie diet being tested for people with metabolically unhealthy obesity because it directly tackles insulin resistance and high fat levels in the liver, which are key issues in this condition. Unlike typical obesity treatments that often rely on medications or surgical interventions, this diet-based approach uses a nutritional strategy to manage and improve metabolic health. By focusing on reducing calorie intake, this method may offer a more natural and sustainable way to enhance insulin sensitivity and regulate glucose levels, which could be a game-changer for patients struggling with these metabolic challenges.

What evidence suggests that a low calorie diet might be an effective treatment for obesity?

Research has shown that eating fewer calories can help people with unhealthy obesity. In this trial, participants with metabolically unhealthy obesity will follow a low-calorie diet. Reducing calorie intake can lead to weight loss and may delay health problems like type 2 diabetes. Studies also suggest it can improve the body's insulin use, which is crucial since people with unhealthy obesity often struggle with insulin. Consuming fewer calories may also enhance overall health and reduce inflammation. This makes a low-calorie diet a promising approach to addressing health issues related to obesity. ^{6 7 8 9 10}

Who Is on the Research Team?

Dmitri Samovski, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with obesity and signs of insulin resistance, such as high blood sugar or HbA1c levels. Participants should have a BMI between 30.0-50.0 kg/m2 if they're obese, or 18.5-24.9 kg/m2 if lean and healthy. They shouldn't have diabetes, liver diseases other than NAFLD, engage in regular exercise, drink excessively, take interfering medications, or be pregnant/lactating.

Inclusion Criteria

People with a certain type of obesity must have a specific level of fat in their liver.

My BMI is either between 18.5-24.9 or 30.0-50.0.

People who are lean and metabolically healthy or have a healthy weight but are metabolically unhealthy should have low levels of fat in their liver.

Exclusion Criteria

I am not on medications that could interfere with the study.

You drink more alcohol than what is recommended for your gender each week.

Are pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Baseline testing of metabolically healthy lean, metabolically healthy obese, and metabolically unhealthy obese participants

Baseline only

1 visit (in-person)

Dietary Intervention

Low calorie diet intervention for metabolically unhealthy obese participants to achieve ~10% weight loss

4-5 months

Follow-up

Participants are monitored for changes in insulin sensitivity and other metabolic parameters after intervention

4-5 months

What Are the Treatments Tested in This Trial?

Interventions

• People with Metabolically Unhealthy Obesity

Trial Overview

The study aims to understand why some obese individuals don't develop type 2 diabetes or heart disease while others do. It involves examining the effects of small extracellular vesicles from humans on metabolic functions in cells and mice and includes a low-calorie diet intervention for those with unhealthy obesity.

How Is the Trial Designed?

Group I: People with Metabolically Unhealthy Obesity - Low Calorie Diet Experimental Treatment 1 Intervention

People with Metabolically Unhealthy Obesity - Persons with obesity with plasma glucose and intrahepatic triglyceride (fat) levels higher than recommended in combination with insulin resistance (defined as HOMA-IR ≥2.5). Dietary intervention - Low calorie diet.

Group II: Metabolically healthy lean - Baseline testing only Active Control 1 Intervention

Metabolically healthy lean - Lean individuals that have good glucose (sugar) control (defined as normal fasting glucose, glucose tolerance and hemoglobin A1c), normal insulin sensitivity (defined as Homeostatic Model Assessment of Insulin Resistance \[HOMA-IR\] \<2.5) and normal intrahepatic triglyceride (fat) levels. Dietary intervention - None.

Group III: People with Metabolically Healthy Obesity - Baseline testing only Active Control 1 Intervention

People with Metabolically Healthy Obesity - Persons with obesity that have good glucose (sugar) control, normal insulin sensitivity and normal intrahepatic triglyceride (fat) levels. Dietary intervention - None.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study of 325 participants who underwent a very low calorie diet (VLCD) program 15 years ago, long-term weight loss maintenance was rare, with only 5.9% managing to keep off more than 10% of their initial body weight.

The study found that while some participants experienced remission of type 2 diabetes shortly after the VLCD, lasting remission was uncommon, and 21.4% developed new glucose intolerance, indicating that the VLCD may not effectively prevent diabetes in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body weight, diabetes incidence vascular events and survival 15 years after very low calorie diet in community medical clinics in the UK. Paisey, R., Daniels, C., Howitt, W., et al.[2022]

In a 90-week study involving five seriously overweight individuals, a self-help group model combined with a very-low-calorie diet led to significant and sustained weight loss, with four participants continuing to lose between 33.7 and 66.8 kg.

All subjects maintained a weight well below their starting point, suggesting that this approach may be effective for long-term obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of a self-help very-low-calorie-diet weight-loss program. Cox, JS., Kreitzman, SN., Coxon, AY., et al.[2018]

In a study of 8 severely obese patients on a low-calorie diet (900 kcal/day) for an average of 33 months, participants lost an average of 44 kg (27% of their initial weight) and showed significant improvements in metabolic health, including better glucose control, blood pressure, and lipid profiles.

The low-calorie diet was well tolerated with only minor side effects, suggesting it can be a safe and effective long-term weight loss strategy for patients who are not candidates for surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-term low-calorie diet in severely obese patients non-eligible for surgery. Alabdali, F., Rueda-Clausen, CF., Robbins, S., et al.[2015]

A study involving 105 patients demonstrated that alternating between moderate low-calorie intake (600 to 1,000 calories) and very restrictive low-calorie intake (230 to 300 calories) effectively promotes weight loss in cases of obesity resistant to traditional diets.

This method is well-accepted by patients and is less monotonous compared to extreme dieting approaches, showing particularly better results in younger patients and those with recent, significant obesity, although it remains effective for long-standing cases as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Alternating low calory diets (200 to 1000 calories), their value in the treatment of resistant obesity]. Mirouze, J., Mary, P., Schmouker, Y., et al.[2007]

Low and very low calorie diets can effectively initiate weight loss and improve obesity-related health issues, but they should only be used under professional supervision due to the risk of severe complications.

Sustained long-term weight loss relies on making permanent lifestyle changes in diet and physical activity, rather than solely relying on low-calorie diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low and very low calorie diets. Atkinson, RL.[2019]

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 very low-calorie diet (VLCD) of 567 kcal for 3 weeks led to an average weight loss of 9 kg and a reduction of 3-4 BMI units in 22 severely obese participants, indicating significant efficacy in weight management.

The VLCD also resulted in improvements in metabolic health, including decreased glucose, insulin, and cholesterol levels, as well as enhanced genomic stability, suggesting potential long-term health benefits for severely obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in anthropometric, biochemical, oxidative, and DNA damage parameters after 3-weeks-567-kcal-hospital-controlled-VLCD in severely obese patients with BMI&#160;&#8805;&#160;35&#160;kg&#160;m-2. Ožvald, I., Božičević, D., Duh, L., et al.[2022]

Very-low-energy diets (VLEDs) combined with behavioral programs resulted in a significant weight loss of -3.9 kg at 12 months compared to behavioral programs alone, indicating their efficacy in long-term weight management.

The study found that VLEDs were generally well-tolerated, with a similar rate of treatment discontinuation compared to control groups and only one serious adverse event reported, suggesting they could be safely used more widely than current guidelines recommend.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials. Parretti, HM., Jebb, SA., Johns, DJ., et al.[2022]

Very low calorie diets can lead to significant weight loss, averaging 20 kg in just 12 weeks, making them effective for treating moderate to severe obesity.

When conducted under careful medical supervision for up to 3 months, these diets are considered safe, with no diet-related fatalities reported in over 10,000 cases, contrasting sharply with earlier liquid protein diets that had serious safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very low calorie diets: their efficacy, safety, and future. Wadden, TA., Stunkard, AJ., Brownell, KD.[2022]

A very-low-calorie diet (VLCD) was effective in promoting significant weight loss and improving lipid profiles in 28 extremely obese subjects over one month, indicating its potential as a safe treatment for obesity.

The VLCD also led to a decrease in hyperinsulinism, which, while not statistically significant, suggests metabolic benefits that could reduce the risk of atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of extreme obesity with a very low calorie diet]. Ivković-Lazar, T.[2009]

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]

In a study of 27 obese patients with type 2 diabetes, adding exercise to a very low-calorie diet (VLCD) resulted in greater fat loss and increased skeletal muscle mitochondrial DNA content compared to the VLCD alone.

While both groups showed similar improvements in insulin-stimulated glucose disposal, only the exercise group experienced significant enhancements in maximum aerobic capacity, indicating that exercise provides additional benefits beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of adding exercise to a 16-week very low-calorie diet in obese, insulin-dependent type 2 diabetes mellitus patients. Snel, M., Gastaldelli, A., Ouwens, DM., et al.[2012]

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]

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