Low Calorie Diet for Obesity

(SEV Trial)

Overseen by Dmitri Samovski, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Affect study outcomes

Disqualifiers: Diabetes, Liver disease, Excessive alcohol, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial aims to understand why some people with obesity develop conditions like type 2 diabetes while others do not. Researchers will study tiny particles called small extracellular vesicles (sEVs) from different groups of people to see how they affect insulin use in cells and mice. The findings could lead to new treatments for obesity-related health issues.

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.

What data supports the effectiveness of the low-calorie diet treatment for people with metabolically unhealthy obesity?

Research shows that very low-calorie diets (VLCDs) can lead to significant weight loss, with patients losing about 20 kg in 12 to 16 weeks and maintaining a portion of this loss over time. Additionally, VLCDs have been shown to improve insulin sensitivity in obese patients with type 2 diabetes, suggesting potential benefits for metabolically unhealthy obesity. ^{1 2 3 4 5}

Is a low-calorie diet safe for treating obesity?

Low-calorie diets (LCDs) and very-low-calorie diets (VLEDs) are generally safe for treating obesity, with minor side effects that are self-limiting. They have been shown to improve metabolic and cardiovascular health, though one serious adverse event, cholecystitis (inflammation of the gallbladder), was reported in a study. Overall, these diets are well-tolerated and can be a safe option for weight loss. ^{5 6 7 8 9}

How does a low calorie diet treatment for metabolically unhealthy obesity differ from other treatments?

A low calorie diet treatment for metabolically unhealthy obesity is unique because it involves alternating between moderate and very low calorie intake, which can be more effective and less monotonous than traditional diets. This approach has shown success in difficult cases of obesity and is well accepted by patients, offering a structured yet flexible method for weight loss. ^{5 10 11 12 13}

Research Team

Dmitri Samovski, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

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.

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

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

Trial Timeline

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

Treatment Details

Interventions

• People with Metabolically Unhealthy Obesity (Behavioral Intervention)

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.

Participant Groups

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+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

Findings from Research

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]

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]

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]

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]

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]

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]

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) 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]

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]

References

1. Serbia pubmed.ncbi.nlm.nih.gov

[Treatment of extreme obesity with a very low calorie diet]. [2009]

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

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

3. United States 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. [2012]

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

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

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

Long-term outcome of a self-help very-low-calorie-diet weight-loss program. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of long-term low-calorie diet in severely obese patients non-eligible for surgery. [2015]

7. Netherlands pubmed.ncbi.nlm.nih.gov

[Overweight. III. Therapeutic strategies for weight reduction]. [2006]

8. England 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. [2022]

9. England 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. [2022]

10. France pubmed.ncbi.nlm.nih.gov

[Alternating low calory diets (200 to 1000 calories), their value in the treatment of resistant obesity]. [2007]

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

Very low calorie diets: their efficacy, safety, and future. [2022]

12. England 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. [2022]

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

Low and very low calorie diets. [2019]