Overweight and ObesityNCT06069622
Role of Caveolin 1 (CAV-1) Deficiency in Response to Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Treatment
An observational study of Overweight and Obesity, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Overweight and Obesity
- What is being tested?
- 24-hour ambulatory blood pressure and Liberal salt diet
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2023to 30 Nov 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ezgi Caliskan Guzelce, MD
Clare Dailey
About this study
Official title: 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
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.
Read the 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
- Being tested
- 24-hour ambulatory blood pressure, Liberal salt diet
- Keywords
- GLP-1 receptor agonist, Weight loss, CAV-1, Blood pressure, ALDO
- Medical subject headings
- Overweight, Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
24-hour ambulatory blood pressureDiagnostic test
Also called Blood collection, Urine collection
24-hour ambulatory blood pressure, blood, and urine will be obtained prior to semaglutide therapy and after 20 weeks of semaglutide therapy.
Liberal salt dietDietary supplement
Participants will be on a liberal salt (about 200 mEq sodium/day) diet for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: 24-hour ambulatory blood pressure; Dietary Supplement: Liberal salt diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 20 weeks
Secondary outcomes (1)
Aldosterone response to GLP-1 RA treatment
The secondary outcome will be changes in 24-hour urinary aldosterone levels in response to GLP-1 RA treatment.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start1 Nov 2023
- Primary completion1 Oct 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Overweight and ObesityStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Charles A. King Trust Postdoctoral Fellowship Program
- Responsible party
- Principal investigator, Ezgi Caliskan Guzelce, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06069622
- Sponsor's protocol ID
- 2023P002452
- Status last verified
- Dec 2025
- First submitted
- 26 Sep 2023
- Last updated
- 10 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06069622
- Acronym / sponsor ID
- 2023P002452
- Conditions
- Overweight and Obesity
- Keywords
- GLP-1 receptor agonist, Weight loss, CAV-1, Blood pressure, ALDO
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Charles A. King Trust Postdoctoral Fellowship Program
- Study start
- 1 Nov 2023 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 6 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Overweight and Obese individuals | – | Diagnostic Test: 24-hour ambulatory blood pressure, Dietary Supplement: Liberal salt dietA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 24-hour ambulatory blood pressureAlso: Blood collection, Urine collection24-hour ambulatory blood pressure, blood, and urine will be obtained prior to semaglutide therapy and after 20 weeks of semaglutide therapy. | Diagnostic test | Overweight and Obese individuals |
| Liberal salt dietParticipants will be on a liberal salt (about 200 mEq sodium/day) diet for 7 days. | Dietary supplement | Overweight and Obese individuals |
Primary outcome
Blood pressure response to GLP-1 RA treatment
Time frame: 20 weeks
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.
Weight loss response to GLP-1 RA treatment
Time frame: 20 weeks
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.
1 secondary outcome
Aldosterone response to GLP-1 RA treatment
Time frame: 20 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Overweight and Obesity, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ezgi Caliskan Guzelce, M.D. (857-544-4290, ecaliskanguzelce@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood pressure response to GLP-1 RA treatment (time frame: 20 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2025.