Clinical trial NCT06541509: Mechanisms of Semaglutide Therapy in Heart Failure Patients
Official title: A Pilot Clinical Trial Investigating Underlying Mechanisms of Semaglutide Therapy in Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Heart Failure
Obesity
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Greenstone Biosciences
First posted: 2024-08-07
Enrollment: 10
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Interleukin-6 (IL-6)
timeFrame: 4 months
measure: Interleukin-8 (IL-8)
timeFrame: 4 months
measure: Tumor Necrosis Factor-alpha (TNF-α)
timeFrame: 4 months
measure: Interferon-gamma (IFN-γ)
timeFrame: 4 months
measure: B-type Natriuretic Peptide (BNP)
timeFrame: 4 months
measure: C-reactive Protein (CRP)
timeFrame: 4 months
measure: Hemoglobin A1C (HgA1C)
timeFrame: 4 months
measure: Complete Blood Count (CBC)
timeFrame: 4 months
measure: Comprehensive Metabolic Panel (Chem 7)
timeFrame: 4 months
measure: Liver Function Tests (LFT)
timeFrame: 4 months
measure: Body mass index
timeFrame: 4 months
Secondary outcomes:
measure: Left ventricular end-systolic volume (LVESV)
timeFrame: 4 months
measure: Left ventricular end-diastolic volume (LVEDV)
timeFrame: 4 months
measure: Myocardial mass
timeFrame: 4 months
measure: Left ventricular ejection fraction (LVEF)
timeFrame: 4 months
measure: Left ventricular filling pressures (E/e')
timeFrame: 4 months
measure: Global longitudinal strain (GLS)
timeFrame: 4 months
measure: Exercise capacity
timeFrame: 4 months
measure: Lean body mass
timeFrame: 4 months
measure: Fat mass
timeFrame: 4 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Greenstone Biosciences
state: California
city: Stanford
country: United States
facility: Stanford Cardiovascular Institute
state: California
city: Ljubljana
country: Slovenia
facility: University Medical Center Ljubljana
Study officials:
References: