Incretin Therapies in Obesity-related HFpEF
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age40+
SponsorColumbia University
About this trial
The central hypothesis to be tested is that patients with obesity and heart failure with preserved ejection fraction (HFpEF) prescribed tirzepatide will demonstrate reductions in measured plasma volume. In conjunction with state-of-the-art body composition analysis and measures of adipokines, this will establish an important mechanism of clinical benefit and inform disease pathophysiology. To accomplish this, this study will perform a 15-month prospective cohort study in 50 patients with obesity and HFpEF who clinically qualify for treatment with tirzepatide. The investigators will serially measure plasma volume and body composition with quantitative magnetic resonance to determine changes over time with tirzepatide treatment.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of heart failure (HF) per the ACC/AHA guidelines with NYHA class II-III symptoms
Left ventricular ejection fraction >= 45% within 6 months of recruitment
At least one of the following: elevated N-terminal pro- B-type natriuretic peptide (NT-proBNP) >=200 pg/ml (>=600 pg/ml with concurrent atrial fibrillation), evidence of structural heart disease (left atrial (LA) enlargement with LA volume index >29 mL/m2 or LA diameter >=40 mm in males/>38= mm in females), elevated filling pressures (resting wedge >15 mmHg or exercise wedge >25 mmHg, lateral E/e' ratio >12 or septal E/e' > 15)
Body mass index (BMI) >30 kg/m2
Disqualifiers
Acute decompensated HF within 4 weeks of screening
Major cardiovascular event within 90 days of screening (myocardial infarction, stroke)
Alternate cause of HFpEF such as cardiac amyloidosis, infiltrative cardiomyopathy, hypertrophic cardiomyopathy, severe valvular disease
Estimated glomerular fibrilation rate (EGFR) <15 ml/min/1.73m2 or dialysis dependence
Trial design
Design model
Single group
Treatments tested in this trial
Tirzepatide
DrugGlucagon-like 1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: TirzepatideExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Plasma volume
Plasma volume is measured using 131-iodine labeled serum albumin. The isotope is injected via an intravenous line and serial blood samples are taken and analyzed using the Blood Volume Analyzer-100 to derive the participant's blood volume and plasma volume. This will be performed at serial visits to determine the effect of tirzepatide therapy on measured plasma volume over time.
Time frame
12 monthsSecondary outcomes
1
Fat mass
Body composition analysis will be performed with quantitative magnetic resonance (QMR). QMR will be performed early morning in a fasting state with participants in uniform hospital gowns and socks. Briefly, the QMR system generates a signal that modifies the spin of hydrogen atoms and uses an algorithm to evaluate the resulting T1 and T2 relaxation curves specific to one of the components of body composition: fat mass, fat-free mass, total body water. This will be performed at serial visits to determine the effect of tirzepatide therapy on fat mass over time.
Time frame
12 months2
Lean mass
Body composition analysis will be performed with QMR. QMR will be performed early morning in a fasting state with participants in uniform hospital gowns and socks. Briefly, the QMR system generates a signal that modifies the spin of hydrogen atoms and uses an algorithm to evaluate the resulting T1 and T2 relaxation curves specific to one of the components of body composition: fat mass, fat-free mass, total body water. This will be performed at serial visits to determine the effect of tirzepatide therapy on lean mass over time.
Time frame
12 monthsOther outcomes
1
Change in total body water
Body composition analysis will be performed with QMR. QMR will be performed early morning in a fasting state with participants in uniform hospital gowns and socks. Briefly, the QMR system generates a signal that modifies the spin of hydrogen atoms and uses an algorithm to evaluate the resulting T1 and T2 relaxation curves specific to one of the components of body composition: fat mass, fat-free mass, total body water. This will be performed at serial visits to determine the effect of tirzepatide therapy on total body water over time.
Time frame
12 months2
Change in serum leptin
Leptin is a hormone associated with fat mass. Serum leptin will be measured serially on tirzepatide therapy to determine if reductions in serum leptin are associated with reduced plasma volume.
Time frame
12 months3
Change in serum adiponectin
Adiponectin is an adipokine that is inversely associated with fat mass. Serum adiponectin will be measured serially on tirzepatide therapy to determine if increases in serum adiponectin are associated with reduced plasma volume.
Time frame
12 months4
Change in KCCQ clinical summary score
The Kansas City Cardiomyopathy Questionnaire (KCCQ) evaluates health status from several principal domains including physical function, social function, symptoms and quality of life. Higher scores indicate better health status, ranging from 0 to 100 points. The clinical summary score will be the exploratory endpoint of interest.
Time frame
12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov