CardiomyopathyPhase 4NCT05371496
Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction
A Phase 4 study testing Semaglutide and Counselling on healthy lifestyle intervention in people with Cardiomyopathy and Heart Failure With Preserved Ejection Fraction (HFpEF), run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this research is to find out if an aggressive intervention to lose weight, will improve symptoms in patients with obesity-related cardiomyopathy, which is also known as the obese phenotype of heart failure with preserved ejection fraction (HFpEF). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiomyopathy, Heart Failure With Preserved Ejection Fraction (HFpEF), Obesity
- What is being tested?
- Semaglutide and Counselling on healthy lifestyle intervention
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2022to 17 Jul 2026
- Phase
- Phase 4
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
Who may be able to join
- BMI ≥ 30.0 kg/m2.
- NYHA Class II-IV.
- LVEF ≥ 50 % within the preceding year.
- No hospitalizations due to heart failure in the preceding 30 days.
- At least one of the following:
- Mean PCWP ≥ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≥ 15 mmHg documented during catheterization at rest, or PCWP or LVEDP ≥ 25 mmHg documented during catheterization at exercise.
- If BMI < 35.0: NT-proBNP ≥ 220 pg/mL (for patients with sinus rhythm) or NT-proBNP ≥ 660 pg/mL (for patients with persistent/permanent atrial fibrillation); if BMI ≥ 35.0: NT-proBNP ≥ 125 pg/mL (for patients in sinus rhythm) or NT-proBNP ≥ 375 pg/mL (for patients with persistent/ permanent atrial fibrillation) at screening (NT-proBNP analyzed by the central laboratory) in combination with at least one of the following (documented by echocardiography within 12 months prior to or at screening): i. Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥ 15. ii. PA systolic pressure > 35 mmHg. iii. Left atrial (LA) enlargement (LA width ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20.0 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2). iv. LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm
- Hospitalization with a primary diagnosis of decompensated heart failure which required intravenous (IV) loop diuretic treatment, within the previous 12 months in combination with at least two of the following (documented by echocardiography within 12 months prior to or at screening): i. Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥ 15. ii. PA systolic pressure > 35 mmHg. iii. LA enlargement (LA width ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20.0 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2). iv. LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm. v. Ongoing use of diuretic therapy for at least 30 days prior to screening.
Who cannot join
- Cardiovascular-related:
- Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
- Systolic blood pressure > 160 mmHg at screening.
- Planned coronary, carotid or peripheral artery revascularization.
- Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, primary pulmonary arterial hypertension, chronic obstructive pulmonary disease, right heart failure due to pulmonary disease, complex congenital heart disease, anemia, or more than moderate mitral or aortic heart valve disease).
- Amyloid cardiomyopathy may be present in 5-15% of patients presenting with the clinical syndrome of HFpEF,60-62 and patients with amyloid may respond differently to WL intervention. To enhance the scientific rigor of the trial by ensuring a homogenous population of true primary HFpEF, we will carefully evaluate for the presence of amyloid using the approach outlined in a recent scientific statement from the AHA,63 which is also consistent with our current clinical practice.
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- Specifically, potential participants will be evaluated for clues or risk factors for underlying cardiac amyloid including intolerance to antihypertensives, hypotension, orthostatic intolerance, persistent low-grade elevation in troponin, low QRS voltage on ECG, unexplained AV block or prior pacemaker, unexplained LV or RV wall thickening, impaired LV global longitudinal strain with apical sparing by echocardiography, family history of cardiomyopathy, neuropathy, autonomic dysfunction, carpal tunnel syndrome, lumbar spinal stenosis, family history of polyneuropathy, or black race. Patients with these risk factors will undergo screening evaluation for amyloid prior to consent in CAMEO-SEMA as part of best clinical practice. This includes screening for monoclonal light chain as first step, followed by hematology consultation if the screen is positive. Patients with risk factors but no monoclonal light chain will then undergo Tc-99m-PYP scan to rule out cardiac amyloid.
- Obesity-related:
- Bariatric surgery prior to screening within 5 years of screening or planned bariatric surgery within the trial time course.
- A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records.
- Glycemia-related:
- HbA1c ≥ 10.0% based on latest available value from medical records, not older than 3 months
- History of type 1 diabetes (history of gestational diabetes is allowed).
- Treatment with any GLP-1 receptor agonist within 90 days prior to the day of screening.
- General health and safety:
- Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- Presence of acute pancreatitis within the last 180 days prior to screening.
- History or presence of chronic pancreatitis.
- End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis.
- Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.
- Known or suspected hypersensitivity to trial product(s) or related products.
- Participation in any clinical trial of an approved or non-approved device for the treatment of heart failure or obesity within 30 days before screening.
- Receipt of any investigational medicinal product within 30 days before screening.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
- Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Evaluation of the Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction (CAMEO-SEMA)
The purpose of this research is to find out if an aggressive intervention to lose weight, will improve symptoms in patients with obesity-related cardiomyopathy, which is also known as the obese phenotype of heart failure with preserved ejection fraction (HFpEF).
- Being tested
- Semaglutide, Placebo, Counselling on healthy lifestyle intervention
- Keywords
- Semaglutide, Hemodynamics, Pathophysiology
- Medical subject headings
- Cardiomyopathies, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
3.0 mg/ml (titrated to 2.4 mg) subcutaneous once weekly for 12 months
PlaceboDrug
Matched placebo with no active drug once weekly for 12 months
Counselling on healthy lifestyle interventionBehavioural
All participants will receive counselling on healthy lifestyle intervention including limiting consumption of salt, red meat, saturated or trans fats, sweets, and sugar-sweetened beverages, and how to restrict calorie intake (500 kcal/day deficit) in consultation with a trained study dietician. Regular physical activity >150 minutes per week will be encouraged.
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide Treatment | Active comparator | Subjects will receive Semaglutide once weekly in addition to counselling on healthy lifestyle intervention Receives: Drug: Semaglutide; Behavioral: Counselling on healthy lifestyle intervention |
| Placebo Treatment | Placebo comparator | Subjects will receive matching placebo once weekly in addition to counselling on healthy lifestyle intervention Receives: Drug: Placebo; Behavioral: Counselling on healthy lifestyle intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Capillary Wedge Pressure (PCWP)
Change in PCWP during exercise, reported in mmHG
Measured: Baseline, 12 months
Secondary outcomes (28)
Trans-cardiac uptake of free fatty acids (FFA) at rest
Change in trans-cardiac uptake of FFA will be measured using arterial and coronary sinus blood samples collected at rest during cardiac catheterization procedure.
Measured: Baseline, 12 months
Trans-cardiac uptake of free fatty acids (FFA) during exercise
Change in trans-cardiac uptake of FFA will be measured using arterial and coronary sinus blood samples collected during the exercise portion of the cardiac catheterization procedure.
Measured: Baseline, 12 months
Trans-cardiac uptake of glucose at rest
Change in trans-cardiac uptake of glucose will be measured using arterial and coronary sinus blood samples collected at rest during the cardiac catheterization procedure.
Measured: Baseline, 12 months
Trans-cardiac uptake of glucose during exercise
Change in trans-cardiac uptake of glucose will be measured using arterial and coronary sinus blood samples collected during the exercise portion of the cardiac catheterization procedure.
Measured: Baseline, 12 months
Trans-cardiac uptake of ketone bodies at rest
Change in trans-cardiac uptake of ketone bodies will be measured using arterial and coronary sinus blood samples collected at rest during the cardiac catheterization procedure.
Measured: Baseline, 12 months
Trans-cardiac uptake of ketone bodies during exercise
Change in trans-cardiac uptake of ketone bodies will be measured using arterial and coronary sinus blood samples collected during the exercise portion of the cardiac catheterization procedure.
Measured: Baseline, 12 months
Left ventricular (LV) global longitudinal strain
Change in LV global longitudinal strain will be assessed by echocardiography conducted during the cardiac catheterization procedure
Measured: Baseline, 12 months
Left Atrial (LA) reservoir strain
Change in LA reservoir strain will be assessed by echocardiography conducted during the cardiac catheterization procedure
Measured: Baseline, 12 months
Right Ventricular (RV) free wall strain
Change in RV free wall strain will be assessed by echocardiography conducted during the cardiac catheterization procedure
Measured: Baseline, 12 months
Myocardial mass
Change in myocardial mass will be measured by CMR imaging.
Measured: Baseline, 12 months
Myocardial volume
Change in myocardial volume will be measured by CMR imaging.
Measured: Baseline, 12 months
Myocardial fat content
Change in myocardial fat content will be measured by CMR imaging.
Measured: Baseline, 12 months
Body fat mass
Change in body fat mass will be measured using dual X-ray absorptiometry (DEXA)
Measured: Baseline, 12 months
Visceral fat content
Change in visceral fat content will be measured using limited abdominal MRI
Measured: Baseline, 12 months
Total blood volume
Change in total blood volume will be assessed by using the radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY).
Measured: Baseline, 12 months
Total plasma volume
Change in total plasma volume will be assessed by using the radiolabeled iodinated albumin (131I, 5-25 μCu) indicator dilution technique (BVA-100 Blood Volume Analyzer, Daxor Corp, NY).
Measured: Baseline, 12 months
Change in Quality of Life (QOL) as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 (worst) and 100 (the best possible status), where the higher score reflected better health status.
Measured: Baseline, 12 months
Change in skeletal muscle mass
Change in skeletal muscle mass will be determined using DEXA scan
Measured: Baseline, 12 months
Change in cardiac chamber mass
Change in cardiac chamber mass and volumes will be measured by CMR imaging
Measured: Baseline, 12 months
Proportion of patients that no longer fulfill hemodynamic criteria for HFpEF at end of trial
Proportion of patients that no longer fulfill hemodynamic criteria for HFpEF at end of trial, defined as resting PAWP<15 and exercise PAWP<25
Measured: 12 months
Change in peak volume of oxygen
Volume of Oxygen (VO2)
Measured: Baseline, 12 months
Change in markers of insulin sensitivity
Insulin (mIU/L)
Measured: Baseline, 12 months
Change in adipocyte cell size
Adipocyte cell size will be determined using methylene blue staining and microscopy.
Measured: Baseline, 12 months
Change in pulmonary arterial pressure at rest
Pulmonary Arterial Pressure is the measure of pressure that the heart uses to pump blood from the heart to the lungs. Pulmonary Arterial Pressure will be determined by a right heart catheterization at rest and measured in mmHg.
Measured: Baseline, 12 months
Change in pulmonary arterial pressure at exercise
Pulmonary Arterial Pressure is the measure of pressure that the heart uses to pump blood from the heart to the lungs. Pulmonary Arterial Pressure will be determined by a right heart catheterization at exercise and measured in mmHg.
Measured: Baseline, 12 months
Change in right atrial pressure
Right Atrial Pressure is the blood pressure in the right atrium.
Measured: Baseline, 12 months
Change in cardiac output
Cardiac output (L/min) is the total volume of blood moved by the heart per minute. Cardiac output is measured during right heart catheterization at exercise
Measured: Baseline, 12 months
Change in pulmonary vascular resistance from rest to peak exercise
Change in pulmonary vascular resistance will be measured in ΔWoods Units
Measured: Baseline, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2022
- Study start6 Sep 2022
- Primary completion17 Jul 2026
- Study completion17 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CardiomyopathyStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Barry Borlaug, Mayo Clinic
- Investigators
- Barry Borlaug, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05371496
- Sponsor's protocol ID
- 22-000522
- Status last verified
- Aug 2026
- First submitted
- 9 May 2022
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No