Cardiac and Metabolic Effects of Semaglutide in Heart Failure With Preserved Ejection Fraction

NCT05371496 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: 22-000522
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Obesity; Cardiomyopathy; Heart Failure With Preserved Ejection Fraction (HFpEF)

Outcome Measures

Primary Outcomes (1)

• Pulmonary Capillary Wedge Pressure (PCWP)

  Change in PCWP during exercise, reported in mmHG

  Baseline, 12 months

Secondary Outcomes (17)

• Trans-cardiac uptake of free fatty acids (FFA) at rest

  Baseline, 12 months

• Trans-cardiac uptake of free fatty acids (FFA) during exercise

  Baseline, 12 months

• Trans-cardiac uptake of glucose at rest

  Baseline, 12 months

• Trans-cardiac uptake of glucose during exercise

  Baseline, 12 months

• Trans-cardiac uptake of ketone bodies at rest

  Baseline, 12 months

Study Arms (2)

Semaglutide Treatment

ACTIVE COMPARATOR

Subjects will receive Semaglutide once weekly in addition to counselling on healthy lifestyle intervention

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

Drug: Placebo; Behavioral: Counselling on healthy lifestyle intervention

Interventions

Placebo DRUG

Matched placebo with no active drug once weekly for 12 months

Placebo Treatment

Semaglutide DRUG

3.0 mg/ml (titrated to 2.4 mg) subcutaneous once weekly for 12 months

Semaglutide Treatment

Counselling on healthy lifestyle intervention BEHAVIORAL

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.

Placebo Treatment; Semaglutide Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• Mayo Clinic: lead
• United States Department of Defense: collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Cardiomyopathies; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Barry Borlaug, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 12, 2022
• Study Start: September 6, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)