Weight Loss for Obesity

Overseen By Jared Greiner, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Boulder

Must not be taking: Blood thinners, Statins

Disqualifiers: Smoking, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 17

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Changes in adipose tissue biology are now recognized as a key factor underlying the increased risk of metabolic and cardiovascular disease with obesity. Clinical interest in adipocyte-derived extracellular vesicles (Ad-EVs) has intensified due to their potential as circulating biomarkers of adipose tissue health and systemic messengers, regulators and mediators of cardiometabolic health and disease with obesity. The investigators hypothesize that elevated Ad-EVs in adults with obesity will be negatively associated with endothelium-dependent vasodilation. Furthermore, the investigators hypothesize that in adults with obesity, intentional weight loss-induced reduction in circulating Ad-EVs is associated with greater endothelium-dependent vasodilation.

Will I have to stop taking my current medications?

The trial requires that you stop taking blood thinners, clotting medications, and statin medications if you are currently on them.

Is the weight loss treatment generally safe for humans?

Some weight loss medications have been linked to serious side effects, including heart and kidney problems, and have been withdrawn from the market due to safety concerns. Dietary supplements for weight loss often lack rigorous testing and regulatory oversight, which means their safety is not well-established. It's important to monitor the safety of these treatments continuously. ^{1 2 3 4 5}

How does the weight loss treatment for obesity differ from other treatments?

This weight loss treatment for obesity is unique because it emphasizes a combination of caloric restriction, nutritional education, exercise, behavioral modification, and ongoing support, rather than relying solely on medication or surgery. It focuses on achieving a healthier weight rather than an ideal weight, and aims to maintain weight loss through lifestyle changes and support. ^{6 7 8 9 10}

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

Surgical weight loss treatments have been shown to improve obesity-related health problems and quality of life, although the long-term sustainability of weight loss and its effects on health are still being studied. Surgery is currently considered the most effective option for significant weight loss in people with severe obesity. ^{11 12 13 14 15}

Who Is on the Research Team?

Christopher DeSouza, PhD

Principal Investigator

University of Colorado, Boulder

Are You a Good Fit for This Trial?

This trial is for adults with obesity who are interested in losing weight without using drugs. The study focuses on how fat cells communicate and influence heart health during weight loss.

Inclusion Criteria

BMI >25 kg/m2 for Phase 2. Rationale for defining obesity as BMI >25 kg/m2

I am 40 years old or older.

My BMI is under 25.

Exclusion Criteria

My blood pressure is very high (>160/100 mmHg).

I am not pregnant or breastfeeding.

Current smoker

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1

Cross-sectional study to compare circulating Ad-EVs association with obesity-related endothelial dysfunction

2 weeks

2 visits (in-person)

Phase 2

Intervention study to determine effects of 12-week weight loss on circulating Ad-EVs and endothelium-dependent vasodilation

12 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Weight loss

Trial Overview The study looks at the effects of intentional weight loss on tiny particles released by fat cells, called Ad-EVs, and their relationship to blood vessel function.

How Is the Trial Designed?

Group I: Experimental: Phase 2 Experimental Treatment 1 Intervention

Phase 2 employs an intervention study design, to determine in adults with obesity, the effects of intentional weight loss (12-weeks) on circulating Ad-EVs and their effect on endothelium-dependent vasodilation.

Group II: No Intervention: Phase 1 Active Control 1 Intervention

Phase 1 is a cross-sectional study to compare whether circulating Ad-EVs are associated with obesity-related endothelial dysfunction in normal weight adults and adults with obesity.

Who Is Running the Clinical Trial?

University of Colorado, Boulder

Lead Sponsor

Trials

128

Recruited

29,600+

Published Research Related to This Trial

Patients in an academic obesity unit had unrealistic weight loss expectations, with women expecting to lose up to 42% and men 29% of their body weight, despite a median BMI of 40.7 kg/m².

Recognizing gender differences in weight loss expectations is crucial for developing effective obesity treatment programs, and setting realistic goals early on can improve patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient expectations of obesity treatment-the experience from a day-care unit. Linné, Y., Hemmingsson, E., Adolfsson, B., et al.[2015]

In a study of 47 patients who underwent videolaparoscopic sleeve gastrectomy, the average percentage of excess weight loss was 85.46%, indicating significant weight reduction post-surgery.

Quality of life improvements were substantial, with 76.6% of patients reporting excellent to good outcomes on the BAROS questionnaire, and all investigated comorbidities showed clinical improvement after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE. Vargas, GP., Mendes, GA., Pinto, RD.[2022]

In a study analyzing data from 34 surgical practices, it was found that considering patients lost to follow-up as treatment failures does not accurately reflect the effectiveness of obesity surgery, as only 61% of patients returned for one-year follow-up.

Using two different methods to define success, the study showed that 67% of patients who were followed achieved at least a 50% excess weight loss, indicating that follow-up rates do not correlate with actual treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Follow-up on Reporting Success for Obesity Surgery. Renquist, KE., Cullen, JJ., Barnes, D., et al.[2019]

Surgical weight loss procedures significantly improve or resolve obesity-related medical issues for most patients, but the long-term effects on sustained weight loss and health improvements are still uncertain.

The American Society of Bariatric Surgery's new computer registry aims to standardize outcome analysis and improve patient selection for surgeries, which could enhance the effectiveness of weight loss interventions and ultimately improve health outcomes for morbidly obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of obesity surgery. Brolin, RE.[2005]

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]

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]

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 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]

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 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]

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]

Achieving a weight loss of 5-10% (about 5-10 kg) within 3-4 months is realistic and leads to significant health benefits, making it unreasonable to aim for an 'ideal' body weight.

Weight maintenance is the primary goal of obesity management, with about 40% of patients able to sustain significant weight loss for over a year through dietary and behavioral techniques, and this success rate increases to 70% with appetite-modifying drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity--what are the current treatment options? Lean, ME.[2016]

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]

Recent studies indicate that a comprehensive group behavioral program can help obese individuals lose about 9% of their initial weight over 20 weeks, with a maintenance of at least 5% weight loss after one year without further treatment.

To enhance long-term weight loss maintenance, strategies such as increasing physical activity, extending behavioral treatment duration, and combining behavioral methods with pharmacological interventions are recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural treatment of the overweight patient. Wadden, TA., Sarwer, DB., Berkowitz, RI.[2019]

Citations

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

Patient expectations of obesity treatment-the experience from a day-care unit. [2015]

2. Brazil pubmed.ncbi.nlm.nih.gov

QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE. [2022]

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

The Effect of Follow-up on Reporting Success for Obesity Surgery. [2019]

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

Results of obesity surgery. [2005]

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

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

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. England pubmed.ncbi.nlm.nih.gov

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

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. Germany pubmed.ncbi.nlm.nih.gov

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

10. 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]

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

Medical management of obesity. [2005]

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

Obesity--what are the current treatment options? [2016]

14. France pubmed.ncbi.nlm.nih.gov

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

15. England pubmed.ncbi.nlm.nih.gov

Behavioural treatment of the overweight patient. [2019]