Weight Loss Interventions for Obesity
Trial Summary
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.
What data supports the effectiveness of the treatment Roux-en-Y Gastric Bypass or Sleeve Gastrectomy for weight loss?
Roux-en-Y gastric bypass is shown to be one of the most effective treatments for long-term weight loss in severely obese individuals, achieving 60% to 70% excess body weight loss. It works by reducing food intake and absorption, and it has multiple effects on the body's hormones and feelings of fullness.12345
Is Roux-en-Y gastric bypass generally safe for humans?
How is the Behavioral Weight Loss Program, Roux-en-Y Gastric Bypass, or Sleeve Gastrectomy treatment different from other obesity treatments?
This treatment is unique because it combines surgical options like Roux-en-Y Gastric Bypass, which changes how your body processes food, with a Behavioral Weight Loss Program that includes lifestyle changes and support. This comprehensive approach not only targets physical weight loss but also addresses psychological and social factors, offering long-term benefits and maintenance of weight loss.23489
What is the purpose of this trial?
Patients and clinicians need better options to prevent the weight regain that almost universally follows a weight loss intervention. In lay terms, a new, higher "set point" seems to occur after people gain weight. Evidence from some research studies reinforces these observations, showing that processes of energy homeostasis vigorously defend the higher level of adiposity for years, if not permanently. Only bariatric surgery appears to "re-set" to a lower level of adiposity. No clear mechanism has been elucidated to date that explains these phenomena. The current proposal endeavors to address this crucial scientific gap by translating preclinical data into human studies testing novel mechanistic hypotheses. Prior studies in rodents show that a high-fat diet causes inflammation and a cellular response, known as gliosis, within hypothalamic regions regulating energy balance and glucose homeostasis. Evidence further suggests that gliosis might play a pathogenic role in obesity and type 2 diabetes mellitus (T2D) because its development precedes weight gain and impaired glucose homeostasis and its inhibition improves metabolic health. Importantly, gliosis is detectable in mice and humans by magnetic resonance imaging (MRI). Using MRI, the investigators discovered the first evidence of gliosis in obese humans and went on to show associations of gliosis with insulin resistance in humans, independent of the level of adiposity. New findings suggest that people with T2D have more extensive gliosis than is seen in nondiabetic obese subjects. Further findings reveal that gliosis improves, but is not completely reversed, 8 mo. after Roux-en-Y gastric bypass (RYGB) surgery in T2D patients. It remains unknown whether gliosis improves similarly when weight loss occurs by lifestyle change or if the efficacy and durability of weight loss via bariatric surgery is partially explained by its ability to reverse gliosis via an as yet unknown mechanism of action. We therefore propose three studies in humans to discover 1) if hypothalamic gliosis is reversed by a standard behavioral weight loss intervention, 2) if the extent of gliosis predicts successful weight loss during, or weight regain after, behavioral weight loss, and 3) the time course of improvement in gliosis after RYGB and the relation of its improvement to the short- and long-term efficacy of RYGB. Future research would define dietary, environmental, or other risk factors for the development of hypothalamic gliosis in humans. Achieving a better understanding of the role of the brain in obesity and its treatment could open new avenues for research, intervention, and prevention.
Research Team
Ellen Schur, MD, MS
Principal Investigator
University of Washington
Eligibility Criteria
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
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Behavioral Weight Loss Intervention
Participants undergo a standard behavioral weight loss program to assess if hypothalamic gliosis is reversed
Surgical Intervention
Participants undergo Roux-en-Y Gastric Bypass Surgery to evaluate the time course of improvement in gliosis
Follow-up
Participants are monitored for safety and effectiveness after interventions, focusing on gliosis improvement and weight regain
Treatment Details
Interventions
- Behavioral Weight Loss Program
- Roux-en-Y Gastric Bypass or Sleeve Gastrectomy
Behavioral Weight Loss Program is already approved in United States, European Union for the following indications:
- Obesity
- Weight Loss
- Type 2 Diabetes Prevention
- Obesity
- Weight Loss
- Type 2 Diabetes Prevention
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Washington
Lead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator