Weight Loss Interventions for Obesity

Overseen By Roz De Leon

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Washington

Must not be taking: Insulin, DPP-4 inhibitors

Disqualifiers: Hypertension, Coronary artery disease, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different weight loss methods affect the brain and overall metabolic health, with a focus on gliosis, an inflammation in the brain linked to obesity and diabetes. Participants will either follow a Behavioral Weight Loss Program, which emphasizes lifestyle and behavior changes, or undergo bariatric surgery, such as Roux-en-Y Gastric Bypass, to assess the impact on gliosis and weight maintenance. Individuals who have struggled with obesity, particularly those who have previously attempted weight loss methods, may be suitable candidates. The study seeks participants with a BMI of 30 or higher who are not currently in a weight loss program, among other criteria. As an unphased trial, this study offers a unique opportunity to contribute to understanding the impacts of weight loss on brain health.

Will I have to stop taking my current medications?

The trial requires that participants stop using insulin (except for the Surgical Weight Loss group), DPP-4 inhibitors, thiazolidinediones, or medications known to alter metabolic function, such as atypical antipsychotics and corticosteroids.

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

Studies have shown that both the behavioral weight loss program and surgeries like Roux-en-Y gastric bypass and sleeve gastrectomy are generally well-tolerated by patients. Intensive behavioral therapy, which changes eating and exercise habits, has proven effective in many cases without significant side effects. Most participants lose weight safely with this approach.

On the surgical side, research shows that both Roux-en-Y gastric bypass and sleeve gastrectomy lead to significant, long-term weight loss. However, like any surgery, there are some risks. For example, within 30 days after surgery, about 4.6% of patients who underwent sleeve gastrectomy and 6.3% of those who had Roux-en-Y gastric bypass experienced some kind of complication. These rates are relatively low, suggesting that most people handle these surgeries well.

Overall, while both treatments yield positive results, it's important to consider potential risks and discuss them with healthcare providers before deciding on a treatment path. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for obesity because they offer distinct approaches to tackle excess weight. The Behavioral Weight Loss Program emphasizes sustainable lifestyle changes, which can lead to long-term weight management without the need for surgery. Meanwhile, Roux-en-Y Gastric Bypass and Sleeve Gastrectomy are surgical options that often result in significant weight loss more quickly than non-surgical methods by altering the digestive system. These diverse strategies provide options tailored to individual needs, potentially improving outcomes for a broader range of patients.

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

Research has shown that programs focused on changing diet and exercise, such as the Behavioral Weight Loss Program, can help people lose weight and maintain it. In some of these programs, up to 97% of participants lost a significant amount of weight over a year. Participants in this trial may join the Lifestyle Cohort, undergoing the Behavioral Weight Loss Program.

For those considering surgery, Roux-en-Y gastric bypass has resulted in more substantial long-term weight loss. About 68% of people who underwent this surgery lost at least half of their excess weight after three years. Participants in this trial may join the Surgical Cohort, scheduled for Roux-en-Y Gastric Bypass Surgery. Both methods offer advantages, and the best choice depends on individual goals and health needs. ^{1 2 3 6 7}

Who Is on the Research Team?

Ellen Schur, MD, MS

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

This trial is for adults aged 25-64 with obesity, who are eligible for weight loss surgery (Roux-en-Y Gastric Bypass or Sleeve Gastrectomy) and have a BMI of 30-<56 kg/m². Healthy individuals with a BMI of 18.5-24.9 can also participate as controls. Exclusions include poorly controlled hypertension, severe chronic diseases, certain medication use, pregnancy, MRI contraindications, smokers or heavy alcohol users.

Inclusion Criteria

My BMI is between 30 and less than 56 kg/m².

Healthy Weight Controls (HWC): BMI 18.5-24.9 kg/m²

I am between 25 and 64 years old.

Exclusion Criteria

Current smoking/daily use of nicotine containing products (cigarettes, e-cigarettes, vaping or other nicotine containing products) or heavy alcohol use

Severe food allergies

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Behavioral Weight Loss Intervention

Participants undergo a standard behavioral weight loss program to assess if hypothalamic gliosis is reversed

8 months

Surgical Intervention

Participants undergo Roux-en-Y Gastric Bypass Surgery to evaluate the time course of improvement in gliosis

8 months

Follow-up

Participants are monitored for safety and effectiveness after interventions, focusing on gliosis improvement and weight regain

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Weight Loss Program
• Roux-en-Y Gastric Bypass or Sleeve Gastrectomy

Trial Overview The study tests if hypothalamic gliosis related to obesity and diabetes can be reversed by behavioral weight loss programs or bariatric surgery (Roux-en-Y Gastric Bypass or Sleeve Gastrectomy). It will examine the role of brain inflammation in maintaining higher body weights after initial weight loss.

How Is the Trial Designed?

Group I: Lifestyle Cohort Active Control 1 Intervention

Participants Undergoing Behavioral Weight Loss Program

Group II: Surgical Cohort Active Control 1 Intervention

Participants Scheduled for Roux-en-Y Gastric Bypass Surgery

Group III: Healthy Weight Control Cohort Active Control 1 Intervention

Healthy Weight Controls With No Intervention

Behavioral Weight Loss Program is already approved in United States, European Union for the following indications:

Approved in United States as Behavioral Weight Loss Program for:

• Obesity
• Weight Loss
• Type 2 Diabetes Prevention

Approved in European Union as Behavioral Weight Loss Interventions for:

• Obesity
• Weight Loss
• Type 2 Diabetes Prevention

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Bariatric surgery, such as Roux-en-Y gastric bypass and biliopancreatic diversion, is effective for long-term weight loss and reducing health risks in morbidly obese individuals, but it can lead to serious nutritional complications that may require revisional surgery.

In a study of four patients who underwent revisional surgery due to complications, one patient died, highlighting that while revision surgery is rare, it carries increased risks and can involve different surgical approaches depending on the patient's condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisional surgery in severe nutritional complications after bariatric surgical procedures: report of four cases from a single institution and review of the literature. Braga, JGR., Concon, MM., Lima, AP., et al.[2021]

In a study of 85 adolescents who underwent Roux-en-Y gastric bypass (RYGB), adherence to prescribed micronutrient supplementation was only 44-61% over 5 years, leading to significant long-term deficiencies, particularly in iron and vitamin D.

Adolescents who did not adhere to supplementation had lower levels of essential nutrients and a higher prevalence of anemia and deficiencies, highlighting the need for ongoing monitoring and potentially increased supplementation post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Micronutrient intake and biochemistry in adolescents adherent or nonadherent to supplements 5 years after Roux-en-Y gastric bypass surgery. Henfridsson, P., Laurenius, A., Wallengren, O., et al.[2020]

In a study of 617 patients who underwent Roux-en-Y gastric bypass, Medicare beneficiaries experienced similar long-term weight loss and comorbidity resolution as non-Medicare patients after 10 years, indicating the procedure's effectiveness across different insurance statuses.

Despite Medicare patients being older and having a higher preoperative body mass index, their outcomes were equivalent to those of non-Medicare patients, supporting the case for continued Medicare coverage of bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten-year outcomes of Roux-en-Y gastric bypass are equivalent in patients with Medicare disability and non-Medicare patients. Michaels, AD., Mehaffey, JH., Hawkins, RB., et al.[2019]

In a study of 213 type 2 diabetes patients with a BMI of 25 to 32.5 kg/m2, Roux-en-Y gastric bypass (RYGB) was found to be more effective than medical treatment in achieving significant metabolic improvements, with 23.9% of RYGB patients meeting the triple endpoint compared to only 7.0% in the medical group.

However, RYGB was associated with a higher rate of complications (36 vs. 22), highlighting the need to weigh the benefits of improved metabolic outcomes against the risks of surgical complications when considering treatment options for patients with lower BMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year outcomes of Roux-en-Y gastric bypass vs medical treatment in type 2 diabetes with a body mass index lower than 32.5&#160;kg/m2: a multicenter propensity score-matched analysis. Ling, J., Tang, H., Meng, H., et al.[2022]

An interdisciplinary comprehensive weight loss program, combined with a biweekly behavioral maintenance program, helped participants maintain 83% of their initial weight loss after 18 months.

This multi-disciplinary approach, which includes social support and aerobic exercise, is considered the best current treatment for obesity, providing significant long-term health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment of obesity: a behavioral medicine perspective. Pera, V., Clark, MM., Abrams, DB.[2005]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3233993/

Behavioral Treatment of Obesity - PMC This paper provides an overview of the structure and principles of behavioral weight loss treatment. The short- and long-term effectiveness of this approach is ...

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2702878

Behavioral Weight Loss Interventions to Prevent Obesity ... The USPSTF found adequate evidence that behavior-based weight loss maintenance interventions are of moderate benefit. The USPSTF found adequate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5503454/

Behavioral Lifestyle Interventions for Moderate and Severe ... Among the 25 behavioral interventions in the 12 studies, 18 reported percent of participants achieving clinically significant weight loss up to 12 months (32–97 ...

4. hopkinsmedicine.org hopkinsmedicine.org/health/treatment-tests-and-therapies/intensive-behavioral-therapy-for-obesity

Intensive Behavioral Therapy for Obesity Most people find that intensive behavioral therapy can be part of a successful weight-loss plan. This therapy doesn't use any risky weight-loss techniques.

5. cms.gov cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=353

NCD - Intensive Behavioral Therapy for Obesity (210.12) Intensive behavioral counseling and behavioral therapy to promote sustained weight loss through high intensity interventions on diet and exercise. The intensive ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00746265?tab=table

NCT00746265 | Behavioral Treatment for Weight Loss This project compares gold standard cognitive-behavioral therapy (based on LEARN, Diabetes Prevention Program, LOOK Ahead) used in both research and clinical ...

7. apa.org apa.org/obesity-guideline/systematic-evidence-review.pdf

Multicomponent Behavioral Interventions for Weight ... Weight management programs for child and adolescent obesity that included at least 26 hours of contact were effective in helping reduce excess weight. We did ...