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NCT Number: NCT06541509

Mechanisms of Semaglutide Therapy in Heart Failure Patients

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.

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Key information

Conditions

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

Age range

20 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University Medical Center Ljubljana, Ljubljana, Slovenia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

semaglutide

Drug

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.

Primary outcomes

  1. Interleukin-6 (IL-6)

    Time frame: 4 months

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

  2. Interleukin-8 (IL-8)

    Time frame: 4 months

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

  3. Tumor Necrosis Factor-alpha (TNF-α)

    Time frame: 4 months

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

  4. Interferon-gamma (IFN-γ)

    Time frame: 4 months

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

  5. B-type Natriuretic Peptide (BNP)

    Time frame: 4 months

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

  6. C-reactive Protein (CRP)

    Time frame: 4 months

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

  7. Hemoglobin A1C (HgA1C)

    Time frame: 4 months

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

  8. Complete Blood Count (CBC)

    Time frame: 4 months

    Measured using automated hematology analyzer. CBC parameters will be measured in their respective units (e.g., cells per microliter).

  9. Comprehensive Metabolic Panel (Chem 7)

    Time frame: 4 months

    Measured using standard laboratory methods. Chem 7 parameters will be measured in their respective units (e.g., mg/dL, U/L).

  10. Liver Function Tests (LFT)

    Time frame: 4 months

    Measured using standard laboratory methods. LFT parameters will be measured in their respective units (e.g., mg/dL, U/L).

  11. Body mass index

    Time frame: 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.

Secondary outcomes

  1. Left ventricular end-systolic volume (LVESV)

    Time frame: 4 months

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

  2. Left ventricular end-diastolic volume (LVEDV)

    Time frame: 4 months

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

  3. Myocardial mass

    Time frame: 4 months

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

  4. Left ventricular ejection fraction (LVEF)

    Time frame: 4 months

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

  5. Left ventricular filling pressures (E/e')

    Time frame: 4 months

    Measured using echocardiography. Units of measure: numerical value

  6. Global longitudinal strain (GLS)

    Time frame: 4 months

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

  7. Exercise capacity

    Time frame: 4 months

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

  8. Lean body mass

    Time frame: 4 months

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

  9. Fat mass

    Time frame: 4 months

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

Study contacts

Contact information is provided by the study sponsor or research team.

Bojan Vrtovec, MD, PhD

CONTACT

[email protected]

+3861 522 1157

Sabina Frljak, MD, PhD

CONTACT

[email protected]

+3861 522 2844

Sponsors and collaborators

Lead sponsor

University Medical Centre Ljubljana

Other

Collaborators

  • Greenstone Biosciences
  • Stanford University

Registry information

Official study title

A Pilot Clinical Trial Investigating Underlying Mechanisms of Semaglutide Therapy in Heart Failure Patients

Acronym: SEMAHEART

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Aug 7, 2024
Registry last updated
Aug 7, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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