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

Last updated: January 13, 2025
Sponsor: Brigham and Women's Hospital
Overall Status: Active - Recruiting

Phase

N/A

Condition

Obesity

Hypertriglyceridemia

Treatment

Liberal salt diet

24-hour ambulatory blood pressure

Clinical Study ID

NCT06069622
2023P002452
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age ≥18 years, body mass index (BMI) ≥30.0 kg/m2 or ≥27.0 kg/m2 with the presence ofat least one of the following weight-related comorbidities (treated or untreated):hypertension, prediabetes, dyslipidemia, obstructive sleep apnea,

  • Normal screening laboratory values,

  • Systolic BP < 160 mmHg and diastolic BP < 95 mmHg as determined from measurementduring screening, using a random-zero device in the clinic and normalelectrocardiogram, use of anti-hypertensive medications will be allowed except formineralocorticoid receptor antagonists.

Exclusion

Exclusion Criteria:

  • Diabetes mellitus,

  • Treatment with a glucose-lowering agent(s) or anti-obesity medication within 90 daysof screening,

  • Treatment with a GLP-1 receptor agonist within 180 days,

  • Current treatment with beta-blocker, or steroids,

  • Pregnancy,

  • Personal history of pancreatitis,

  • Personal history of cholelithiasis,

  • Previous surgical obesity treatment,

  • Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2or medullary thyroid carcinoma,

  • Medical illness other than hypertension, prediabetes, obstructive sleep apnea, ordyslipidemia,

  • Alcohol intake >12 oz. per week,

  • Tobacco, or recreational drug use

Study Design

Total Participants: 30
Treatment Group(s): 2
Primary Treatment: Liberal salt diet
Phase:
Study Start date:
November 01, 2023
Estimated Completion Date:
October 30, 2025

Study 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.

Connect with a study center

  • Brigham and Women's Hospital

    Boston, Massachusetts 02115
    United States

    Active - Recruiting

+−

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.