NCT06069622

Role of Caveolin 1 (CAV-1) Deficiency in Response to Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Treatment

The Role of Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Treatment of Overweight/Obese Individuals for Improving Adverse Cardiometabolic Phenotype Associated With CAV-1 Deficiency

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 30 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Obesity has become an important public health issue that leads to insulin resistance, diabetes, hypertension, dyslipidemia, and cardiovascular diseases. Although weight loss with calorie restriction and increased physical activity improve these complications, many people fail these lifestyle interventions. Therefore, pharmacologic agents have been used for weight management in addition to lifestyle interventions. In the past few years, one of the widely used pharmacologic agents for weight management is Glucagon-like peptide 1 receptor agonists (GLP1 RAs). Overall, this class of medications improves both metabolic and cardiovascular profiles while causing weight loss, but their effects can vary between individuals. Therefore, it is essential to understand who will respond best to this therapy. Based on previous research on the interaction between a cell membrane molecule, caveolin-1, and glucagon-like peptide 1 receptor, we hypothesize that genetic variations in the caveolin-1 gene explain the variable cardiometabolic responses.

Detailed description

Obesity is a chronic, multifactorial, and relapsing disease with an increasing prevalence that leads to insulin resistance, diabetes mellitus, hypertension, dyslipidemia, and cardiovascular diseases. Weight loss is known to improve metabolic and cardiovascular risk profiles. Although calorie restriction and increased physical activity represent the cornerstone of weight management treatment, clinical guidelines suggest adjunctive pharmacotherapy, particularly for adults with a BMI of 30 kg/m2 or greater or 27 kg/m2 or greater with coexisting conditions. Glucagon-like peptide 1 receptor agonists (GLP1 RAs) are highly effective in inducing weight loss in overweight and obese adults and have also been shown to improve cardiovascular outcomes. Elevated blood pressure (BP) is a well-known cardiovascular risk factor. Although GLP1 RAs improve insulin resistance, dyslipidemia, and type 2 diabetes, the beneficial effects of GLP1 RAs on BP are variable. This proposal's fundamental goal is to understand the mechanisms underlying this variable BP response to GLP1 RAs and investigate whether there is a variable response to weight loss. Caveolin 1 is a protein on cell membrane that interacts with the GLP1 receptor and regulates its action. Our research laboratory previously demonstrated that a common polymorphism of the caveolin 1 (CAV1) gene (minor allele \[C\] at rs926198), which is associated with caveolin 1 deficiency, is strongly associated with higher BP and other components of the metabolic syndrome. This proposal will test the hypothesis that CAV-1 genotype will affect the CV and metabolic responses to treatment of overweight/obese individuals with a GLP-1 RA. Overall, demonstrating that a common variant in the CAV1 gene identifies the blood pressure and weight loss responses to GLP-1 RAs would be a very significant clinical outcome as GLP1 RAs use is rapidly increasing and would help lead to personalized therapy for obesity treatment.

Conditions

• Overweight and Obesity

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	24-hour ambulatory blood pressure	24-hour ambulatory blood pressure, blood, and urine will be obtained prior to semaglutide therapy and after 20 weeks of semaglutide therapy.
DIETARY_SUPPLEMENT	Liberal salt diet	Participants will be on a liberal salt (about 200 mEq sodium/day) diet for 7 days.

Timeline

• Start date: 2023-11-01
• Primary completion: 2026-10-01
• Completion: 2026-11-30
• First posted: 2023-10-06
• Last updated: 2025-12-10

Locations

1 site across 1 country: United States