- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Ezgi Caliskan Guzelce, M.D.
- Phone Number: 857-544-4290
- Email: ecaliskanguzelce@bwh.harvard.edu
Study Contact Backup
- Name: Gail K.Adler, M.D.,PhD.
- Phone Number: 617-732-5666
- Email: gadler@bwh.harvard.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
24-hour ambulatory blood pressure, blood, and urine will be obtained prior to semaglutide therapy and after 20 weeks of semaglutide therapy.
Other Names:
Participants will be on a liberal salt (about 200 mEq sodium/day) diet for 7 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
20 weeks
|
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.
|
20 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Aldosterone response to GLP-1 RA treatment
Time Frame: 20 weeks
|
The secondary outcome will be changes in 24-hour urinary aldosterone levels in response to GLP-1 RA treatment.
|
20 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2023P002452
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Overweight and Obesity
-
University Hospital, LilleNational Research Agency, France; European Union; University of Lille Nord de... and other collaboratorsNot yet recruitingOverweight and Obesity | Overweight, Childhood | Overweight, Infant
-
Washington University School of MedicinePatient-Centered Outcomes Research Institute; Pennington Biomedical Research... and other collaboratorsActive, not recruitingOvernutrition | Nutrition Disorders | Overweight | Body Weight | Pediatric Obesity | Body Weight Changes | Childhood Obesity | Weight Gain | Adolescent Obesity | Obesity, Childhood | Overweight and Obesity | Overweight or Obesity | Overweight AdolescentsUnited States
-
Institut Investigacio Sanitaria Pere VirgiliCompletedObesity, Childhood | Overweight and Obesity | Overweight, ChildhoodSpain
-
Memorial Sloan Kettering Cancer CenterRecruitingObesity | Overweight | Overweight and Obesity | Obese | Overweight or ObesityUnited States
-
Holbaek SygehusUniversity of Copenhagen; University of Florida; University of Minnesota; Hebrew... and other collaboratorsRecruitingChildhood Overweight and ObesityDenmark
-
Universidade do Extremo Sul Catarinense - Unidade...RecruitingObesity | Overweight and Obesity | Obesity; Endocrine | Overweight, Obesity and Other HyperalimentationBrazil
-
Mexican National Institute of Public HealthUNICEFCompleted
-
Universidade do PortoFundação para a Ciência e a Tecnologia; Administração Regional de Saúde do... and other collaboratorsCompletedOverweight and ObesityPortugal
-
University of British ColumbiaTerminatedOverweight and ObesityCanada
-
National Taiwan University HospitalCompleted
Clinical Trials on 24-hour ambulatory blood pressure
-
University of Texas at AustinCompleted
-
University of Texas Southwestern Medical CenterDepartment of UrologyNo longer availableHydronephrosis | Multicystic-dysplastic Kidney
-
University of BurgundyAssociation pour le Développement de la Recherche en Médecine Générale (ADRMG) and other collaboratorsUnknownHypertension | Primary Health Care | Blood Pressure Monitoring, AmbulatoryFrance
-
Insel Gruppe AG, University Hospital BernRecruitingPulmonary Hypertension | Antiphospholipid Syndrome in Pregnancy | Pre-Eclampsia; Complicating PregnancySwitzerland
-
National Heart Centre SingaporeRecruiting
-
Consorci d'Atenció Primària de Salut de l'EixampleInstituto de Salud Carlos IIICompleted
-
Instituto Ecuatoriano del CorazónRecruiting
-
Kaiser PermanentePatient-Centered Outcomes Research InstituteCompleted
-
Karolinska InstitutetDanderyd HospitalRecruitingAtrial Fibrillation | Atrial Flutter | Supraventricular Beat, Premature | Premature Supraventricular Beats | Premature Atrial Complex | Extrasystole, AtrialSweden
-
Mayo ClinicEnrolling by invitationNarcolepsy | Idiopathic HypersomniaUnited States