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Mechanisms of Semaglutide Therapy in Heart Failure Patients

Phase 1
Recruiting
Conditions
Heart Failure
Obesity
Interventions
Registration Number
NCT06541509
Lead Sponsor
University Medical Centre Ljubljana
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
10
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Semaglutide TherapySemaglutideTimepoints: * Baseline (Week 0) * Week 2 (Visit 1) * Week 4 (Visit 2) * Week 12 (Visit 3) * Week 16 (Visit 4) Medication Schedule: Subcutaneous semaglutide (Ozempyc, Novo Nordisk A/S Bagsvaerd, Denmark) First 2 weeks: Semaglutide; 0.25 mg weekly Second 2 weeks: Semaglutide; 0.5 mg weekly Remaining 12 weeks: Semaglutide; 1 mg weekly
Primary Outcome Measures
NameTimeMethod
B-type Natriuretic Peptide (BNP)4 months

Measured using immunoassay. Units of Measure: picograms per milliliter (pg/mL).

Interleukin-6 (IL-6)4 months

Measured using enzyme linked immunosorbent assay (ELISA). Units of Measure: picograms per milliliter (pg/mL).

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).

Interferon-gamma (IFN-γ)4 months

Measured using ELISA. 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).

Interleukin-8 (IL-8)4 months

Measured using ELISA. Units of Measure: picograms per milliliter (pg/mL).

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).

Body mass index4 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.

Tumor Necrosis Factor-alpha (TNF-α)4 months

Measured using ELISA. Units of Measure: picograms per milliliter (pg/mL).

Hemoglobin A1C (HgA1C)4 months

Measured using standard laboratory methods. Units of Measure: percent (%).

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).

Secondary Outcome Measures
NameTimeMethod
Left ventricular filling pressures (E/e')4 months

Measured using echocardiography. Units of measure: numerical value

Myocardial mass4 months

Measured using echocardiography. Units of measure: gram (g)

Global longitudinal strain (GLS)4 months

Measured using echocardiography. Units of measure: percent (%)

Exercise capacity4 months

Measured by 6-minute walk test distance Units of measure: meter (m)

Left ventricular end-systolic volume (LVESV)4 months

Measured using echocardiography. Units of measure: mililiter (mL)

Lean body mass4 months

Measured using dual-energy X-ray absorptiometry Units of measure: gram (g)

Left ventricular ejection fraction (LVEF)4 months

Measured using echocardiography. Units of measure: percent (%)

Left ventricular end-diastolic volume (LVEDV)4 months

Measured using echocardiography. Units of measure: mililiter (mL)

Fat mass4 months

Measured using dual-energy X-ray absorptiometry Units of measure: gram (g)

Trial Locations

Locations (3)

University Medical Center Ljubljana

🇸🇮

Ljubljana, Slovenia

Greenstone Biosciences

🇺🇸

Palo Alto, California, United States

Stanford Cardiovascular Institute

🇺🇸

Stanford, California, United States

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