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Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 20 Years and 80 Years
Eligible Sex
All
Accepts 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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Semaglutide Therapy 		Timepoints: - 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
  • Drug: Semaglutide
    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.

Recruiting Locations

Greenstone Biosciences
Palo Alto, California 94304
Contact:
Mukhtar Ahmed, PhD
mukhtarahmed@greenstonebio.com

Stanford Cardiovascular Institute
Stanford, California 94305
Contact:
Joseph C Wu, MD, PhD
650-736-2246
joewu@stanford.edu

More Details

Status
Recruiting
Sponsor
University Medical Centre Ljubljana

Study Contact

Bojan Vrtovec, MD, PhD
+3861 522 1157
bojan.vrtovec@kclj.si

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.