Heart Failure, Obesity
Conditions
Brief summary
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, primarily used for treatment of type-2 diabetes mellitus. GLP-1 receptors are present on pancreatic islet β-cells, δ-cells and α-cells. Their stimulation increases insulin and somatostatin secretion, and decreases glucagon secretion. In addition, GLP-1 receptor agonists appear to have multiple extrapancreatic actions, which remain poorly defined. In large clinical trials, semaglutide improved the outcomes in obese patients, patients with heart failure with preserved ejection fraction, and decreased the heart failure hospitalizations in patients with type 2 diabetes. The aim of the present study is to investigate the underlying mechanisms of the beneficial clinical effects of semaglutide in the setting of chronic heart failure.
Interventions
DRUGSemaglutide
10 overweight patients with heart failure will be enrolled, including 5 patients with heart failure with preserved ejection fraction (HFpEF) and 5 patients with heart failure with reduced ejection fraction (HFrEF). The diagnosis of HFpEF and HFrEF will be based on the most recent European Society of Cardiology guidelines for the diagnosis and treatment of heart failure. After their baseline blood sample collections, all participants will receive once-weekly subcutaneous semaglutide (Ozempyc, Novo Nordisk A/S Bagsvaerd, Denmark) at a dose of 0.25 mg for 2 weeks, 0.5 mg for 2 weeks, and then 1.0 mg for a period of 12 weeks. At the end of the 3-month and 4-month period, blood sample collections will be repeated. All blood samples will be sent to Stanford Cardiovascular Institute for further analyses. At baseline, and again at 4 months transthoracic echocardiography, 6-minute walk test, and body composition assessment will be performed.
Sponsors
Stanford University
Greenstone Biosciences
University Medical Centre Ljubljana
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age: 20-80 years * Presence of heart failure * Body-mass index 27 kg/m2 or greater * Stable optimally tolerated dosages of heart failure therapies for 3 months * N-terminal pro B-type natriuretic peptide levels \>350 pg/mL
Exclusion criteria
* Presence of type 1 or type 2 diabetes or glycated haemoglobin higher than 6.5% * Pregnancy or potential to become pregnant * Cancer * Liver dysfunction (aspartate aminotransferase and/or alanine aminotransferase \> 3 times upper limits of normal or total bilirubin greater than 1.5 times upper limits of normal) * Renal dysfunction (estimated glomerular filtration rate less than 25 mL/min/1.73 m2) * Hospitalization in the past 3 months for reasons other than heart failure * New York Heart Association (NYHA) functional class I or functional class IV symptoms. * Prior or planned bariatric surgery * Self-reported change in body weight \>11 lbs (5 kg) within 3 months before enrollment * Acute or chronic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body mass index | 4 months | Patient weight will be measured in kilograms and height will be measured in meters. Body mass index (BMI) will be calculated according to the standard formula: weight in kilograms divided by height in meters squared. |
| Interleukin-8 (IL-8) | 4 months | Measured using ELISA. Units of Measure: picograms per milliliter (pg/mL). |
| Tumor Necrosis Factor-alpha (TNF-α) | 4 months | Measured using ELISA. Units of Measure: picograms per milliliter (pg/mL). |
| Interferon-gamma (IFN-γ) | 4 months | Measured using ELISA. Units of Measure: picograms per milliliter (pg/mL). |
| B-type Natriuretic Peptide (BNP) | 4 months | Measured using immunoassay. Units of Measure: picograms per milliliter (pg/mL). |
| C-reactive Protein (CRP) | 4 months | Measured using immunoassay. Units of Measure: picograms per milliliter (pg/mL). |
| Hemoglobin A1C (HgA1C) | 4 months | Measured using standard laboratory methods. Units of Measure: percent (%). |
| Complete Blood Count (CBC) | 4 months | Measured using automated hematology analyzer. CBC parameters will be measured in their respective units (e.g., cells per microliter). |
| Comprehensive Metabolic Panel (Chem 7) | 4 months | Measured using standard laboratory methods. Chem 7 parameters will be measured in their respective units (e.g., mg/dL, U/L). |
| Liver Function Tests (LFT) | 4 months | Measured using standard laboratory methods. LFT parameters will be measured in their respective units (e.g., mg/dL, U/L). |
| Interleukin-6 (IL-6) | 4 months | Measured using enzyme linked immunosorbent assay (ELISA). Units of Measure: picograms per milliliter (pg/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular end-diastolic volume (LVEDV) | 4 months | Measured using echocardiography. Units of measure: mililiter (mL) |
| Myocardial mass | 4 months | Measured using echocardiography. Units of measure: gram (g) |
| Left ventricular ejection fraction (LVEF) | 4 months | Measured using echocardiography. Units of measure: percent (%) |
| Left ventricular filling pressures (E/e') | 4 months | Measured using echocardiography. Units of measure: numerical value |
| Global longitudinal strain (GLS) | 4 months | Measured using echocardiography. Units of measure: percent (%) |
| Exercise capacity | 4 months | Measured by 6-minute walk test distance Units of measure: meter (m) |
| Lean body mass | 4 months | Measured using dual-energy X-ray absorptiometry Units of measure: gram (g) |
| Fat mass | 4 months | Measured using dual-energy X-ray absorptiometry Units of measure: gram (g) |
| Left ventricular end-systolic volume (LVESV) | 4 months | Measured using echocardiography. Units of measure: mililiter (mL) |
Countries
Slovenia, United States
Contacts
Primary ContactBojan Vrtovec, MD, PhD
Backup ContactSabina Frljak, MD, PhD
Outcome results
None listed