Weight Loss for Obesity

Overseen By Sophia Bowen

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Hormone replacements, blood thinners

Disqualifiers: Diabetes, Thyroid disease, Lung disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this intervention study is to learn about how weight loss impacts molecular signaling of intermuscular adipose tissue (IMAT) in individuals with obesity. The main question it aims to answer is how inflammatory molecules secreted by IMAT promote muscle insulin resistance and inflammation, and how these same molecules are diminished after weight loss. Following screening visits involving body composition measures, blood testing, strength testing, and a thigh muscle biopsy, participants will go through a 12-week dietary intervention for weight loss. After 12 weeks, this will be followed by the same testing and biopsies that were completed before the intervention. Researchers will then compare outcomes of individuals who lost weight to individuals who did not lose weight.

Will I have to stop taking my current medications?

The trial requires that you do not take hormone replacement drugs, blood thinners, or thiazoladinediones. If you are on these medications, you would need to stop taking them to participate.

What data supports the effectiveness of the treatment Diet for weight loss in obesity?

Research shows that a combination of dieting and increased exercise is more effective for weight loss than either approach alone, with moderate calorie restriction leading to an average weight loss of about 5 kg after one year. Additionally, adding behavioral therapy, especially with spousal participation, can enhance the effectiveness of dietary measures, resulting in an average weight loss of about 7 kg after one year. ^{1 2 3 4 5}

Is the weight loss treatment generally safe for humans?

There is a lack of rigorous testing and regulatory oversight for many weight loss supplements, which means their safety is not well-established. Some herbal products used for weight loss have been associated with adverse reactions, and several anti-obesity medications have been withdrawn from the market due to safety concerns. ^{6 7 8 9 10}

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

The diet treatment for obesity is unique because it focuses on modifying dietary intake patterns and macronutrient composition, such as low-carbohydrate or low-fat diets, to achieve weight loss through caloric restriction. Unlike drug treatments or surgical options, dietary interventions aim to facilitate adherence and long-term weight maintenance by tailoring the diet to individual needs and preferences. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for generally healthy men and women aged 18-70 with obesity (BMI between 30-40) who exercise less than one hour per week. It includes both pre or postmenopausal individuals. People who don't meet these criteria cannot participate.

Inclusion Criteria

BMI between 30-40

Less than 1 hour of exercise per week

I am a woman who may or may not have gone through menopause.

Exclusion Criteria

Pregnant or breastfeeding

I have a history of lung disease.

Active use of nicotine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo a 12-week dietary intervention for weight loss using low calorie meal replacement shakes

12 weeks

Weekly check-ins (virtual or in-person)

Follow-up

Participants are monitored for changes in muscle strength, insulin sensitivity, IMAT content, body weight, and muscle mass after the intervention

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Diet

Trial Overview The study investigates how a diet-induced weight loss over a period of 12 weeks affects the molecular signaling in muscle fat tissue, which may influence muscle strength and insulin sensitivity in obese individuals.

Participant Groups

Group I: Diet Weight Loss Experimental Treatment 1 Intervention

Low calorie meal replacement shakes

Group II: Delayed Intervention Active Control 1 Intervention

Normal feeding

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

A systematic review of 32 trials found that moderate calorie restriction leads to an average weight loss of about 5 kg after one year, making it the most effective dietary intervention for obesity.

Combining dieting with increased physical activity and active support, such as behavioral therapy, significantly enhances weight loss outcomes, with participants losing around 7 kg after one year when spousal support is included.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity: weight loss without drugs: a balanced diet avoiding high-calorie foods, plus exercise. [2007]

Current dietary treatments for obesity primarily focus on reducing caloric intake based on the assumption that obese individuals eat too much, which has shown limited long-term effectiveness, with an average maximum weight loss of only 8.5%.

The success of these interventions is largely influenced by the initial weight of the participants, suggesting that the approach needs reevaluation to consider the quality of food intake rather than just quantity, and to improve the overall effectiveness of obesity treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatments of obesity. Bennett, W.[2019]

In a study of 397 obese individuals at a university outpatient weight loss clinic, it was found that those with higher initial body weights had unrealistic expectations for weight loss, often desiring losses 2 to 3 times greater than the recommended 5% to 10%.

The study revealed that initial body weight was the strongest predictor of patients' evaluations of their treatment outcomes, indicating a therapeutic challenge where even successful weight loss may be perceived as disappointing by heavier patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obese patients' perceptions of treatment outcomes and the factors that influence them. Foster, GD., Wadden, TA., Phelan, S., et al.[2022]

In an 18-month study involving 101 overweight participants, those on a moderate-fat Mediterranean diet lost an average of 4.1 kg, while those on a low-fat diet gained weight, highlighting the effectiveness of the Mediterranean diet for weight loss.

The moderate-fat diet not only resulted in better weight loss outcomes but also had higher adherence rates, with 54% of participants sticking with the diet compared to only 20% in the low-fat group, suggesting it may be a more sustainable option for long-term weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults. McManus, K., Antinoro, L., Sacks, F.[2022]

In a review of 50 weight-loss studies from the 1980s, participants typically lost an average of 12.8 pounds during a 13-week program but regained about 4.3 pounds in the following 6.5 months, indicating limited long-term efficacy of dieting techniques.

Only one study assessed improvements in physical health during weight loss, and very few participants transitioned from clinical to nonclinical obesity levels, suggesting that traditional dieting methods may not effectively address obesity as a health issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of weight-loss programs. Cogan, JC., Rothblum, ED.[2006]

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]

Diet and exercise alone have not proven effective for sustained weight loss in most obese individuals, while surgical interventions can lead to prolonged weight loss but may result in rebound weight gain over time.

The authors propose a new framework for evaluating medical devices aimed at treating obesity, focusing on a benefit-risk assessment to guide the development and approval of these devices, which was discussed at an FDA workshop and advisory panel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk paradigm for clinical trial design of obesity devices: FDA proposal. Lerner, H., Whang, J., Nipper, R.[2021]

A study analyzing 66 reports of adverse reactions to dietary supplements for weight control found that 64% of these reactions were serious, indicating significant safety concerns associated with their use.

The most commonly affected systems included the cardiovascular (26%) and gastrointestinal (17%) systems, highlighting the potential risks of self-medicating with these herbal products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System. Mazzanti, G., Vitalone, A., Da Cas, R., et al.[2021]

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]

A review of the first 50 websites on 'weight loss diets' revealed that only 3 provided reliable dietary advice, while most promoted questionable supplements and slimming aids.

Many websites failed to address the potential dangers of extreme diets, such as very low calorie diets, which could pose serious health risks to users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slimming on the Internet. Miles, J., Petrie, C., Steel, M.[2020]

Weight reduction is crucial for managing obesity and its related conditions like diabetes and hypertension, and both high-carbohydrate/low-fat and higher-protein/low-carbohydrate diets can lead to fat loss if calorie intake is sufficiently low.

For bariatric patients, low-calorie diets, protein-sparing modified fasts, and modified-carbohydrate diets are the most effective for compliance and long-term weight maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The diet prescription for obesity. What works? Holtmeier, KB., Seim, HC.[2005]

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]

Low-fat diets in obese patients result in modest weight loss of 3-4 kg over 3 years, while calorie-controlled diets show better outcomes with 6-7 kg weight loss at 4 years, although long-term data is limited.

Bariatric surgery, such as gastric bypass, can lead to significant weight loss (up to 25% over 10 years) and reduce mortality and comorbidities, but it carries risks of nutritional deficiencies and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. Clifton, PM.[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]

References

1. France pubmed.ncbi.nlm.nih.gov

Obesity: weight loss without drugs: a balanced diet avoiding high-calorie foods, plus exercise. [2007]

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

Dietary treatments of obesity. [2019]

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

Obese patients' perceptions of treatment outcomes and the factors that influence them. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults. [2022]

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

Outcomes of weight-loss programs. [2006]

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

Dietary supplements and alternative therapies for obesity: A Perspective from The Obesity Society's Clinical Committee. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Benefit-risk paradigm for clinical trial design of obesity devices: FDA proposal. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Suspected adverse reactions associated with herbal products used for weight loss: spontaneous reports from the Italian Phytovigilance System. [2021]

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

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

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

Slimming on the Internet. [2020]

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

The diet prescription for obesity. What works? [2005]

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

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

13. England pubmed.ncbi.nlm.nih.gov

Dietary treatment for obesity. [2022]

14. 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]

15. 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]