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

NCT06069622 | Recruiting DMC

• 1 other identifier: 2023P002452
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Overweight and Obesity

Keywords

GLP-1 receptor agonist; Weight loss; CAV-1; Blood pressure; ALDO

Outcome Measures

Primary Outcomes (2)

• Blood pressure response to GLP-1 RA treatment

  The primary outcome will be the change (pre- treatment minus post-treatment) in mean 24-hour ambulatory systolic BP on a controlled dietary sodium intake in both CAV1 non-risk and risk genotypes.

  20 weeks

• Weight loss response to GLP-1 RA treatment

  The primary outcome will be the mean percent change (pre- treatment minus post-treatment) in body weight in both CAV1 non-risk and risk genotypes.

  20 weeks

Secondary Outcomes (1)

• Aldosterone response to GLP-1 RA treatment

  20 weeks

Study Arms (1)

Overweight and Obese individuals

A group of overweight and obese men and women whose body mass index (BMI) is ≥30.0 kg/m2 or ≥27.0 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, prediabetes, dyslipidemia, obstructive sleep apnea whose treating clinicians have elected to start on semaglutide.

Diagnostic Test: 24-hour ambulatory blood pressure; Dietary Supplement: Liberal salt diet

Interventions

24-hour ambulatory blood pressure DIAGNOSTIC_TEST

24-hour ambulatory blood pressure, blood, and urine will be obtained prior to semaglutide therapy and after 20 weeks of semaglutide therapy.

Also known as: Blood collection, Urine collection

Overweight and Obese individuals

Liberal salt diet DIETARY_SUPPLEMENT

Participants will be on a liberal salt (about 200 mEq sodium/day) diet for 7 days.

Overweight and Obese individuals

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Age ≥18 years, men and women who have body mass index (BMI) ≥30.0 kg/m2 or ≥27.0 kg/m2 with the presence of at least one of the weight-related comorbidities

You may qualify if:

• Age ≥18 years, body mass index (BMI) ≥30.0 kg/m2 or ≥27.0 kg/m2 with the presence of at 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 measurement during screening, using a random-zero device in the clinic and normal electrocardiogram, use of anti-hypertensive medications will be allowed except for mineralocorticoid receptor antagonists.

You may not qualify if:

• Diabetes mellitus,
• Treatment with a glucose-lowering agent(s) or anti-obesity medication within 90 days of 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 2 or medullary thyroid carcinoma,
• Medical illness other than hypertension, prediabetes, obstructive sleep apnea, or dyslipidemia,
• Alcohol intake \>12 oz. per week,
• Tobacco, or recreational drug use

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Charles A. King Trust Postdoctoral Fellowship Program: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

White blood cells

MeSH Terms

Conditions

Overweight; Obesity; Weight Loss

Interventions

Blood Specimen Collection; Urine Specimen Collection

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Ezgi Caliskan Guzelce, M.D.

CONTACT

857-544-4290; ecaliskanguzelce@bwh.harvard.edu

Gail K.Adler, M.D.,PhD.

CONTACT

617-732-5666; gadler@bwh.harvard.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 26, 2023
• First Posted: October 6, 2023
• Study Start: November 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)