Mechanisms of Semaglutide Therapy in Heart Failure Patients

NCT ID: NCT06541509

Last Updated: 2024-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-10

Study Completion Date

2025-09-01

Brief Summary

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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

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Conditions

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Heart Failure Obesity

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Semaglutide

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role collaborator

Greenstone Biosciences

UNKNOWN

Sponsor Role collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Greenstone Biosciences

Palo Alto, California, United States

Site Status RECRUITING

Stanford Cardiovascular Institute

Stanford, California, United States

Site Status RECRUITING

University Medical Center Ljubljana

Ljubljana, , Slovenia

Site Status RECRUITING

Countries

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United States Slovenia

Central Contacts

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Bojan Vrtovec, MD, PhD

Role: CONTACT

+3861 522 1157

Sabina Frljak, MD, PhD

Role: CONTACT

+3861 522 2844

Facility Contacts

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Mukhtar Ahmed, PhD

Role: primary

Joseph C Wu, MD, PhD

Role: primary

650-736-2246

Bojan Vrtovec, MD, PhD

Role: primary

+3861 522 1157

Sabina Frljak, MD, PhD

Role: backup

+3861 522 2844

Other Identifiers

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SEMAHEART

Identifier Type: -

Identifier Source: org_study_id

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