Incretin Therapies in Obesity-related HFpEF

NCT07554638 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: AAAV9609
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Heart Failure, Diastolic; Obesity; Heart Failure With Preserved Ejection Fraction

Outcome Measures

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.

  12 months

Secondary Outcomes (2)

• Fat mass

  12 months

• Lean mass

  12 months

Other Outcomes (5)

• Change in total body water

  12 months

• Change in serum leptin

  12 months

• Change in serum adiponectin

  12 months

Study Arms (1)

Tirzepatide

EXPERIMENTAL

After a 3-month control period, participants will be prescribed tirzepatide and undergo serial plasma volume measurement and body composition analysis. Participants will be prescribed tirzepatide under the brand name Monjauro if they have diabetes, and under the brand name Zepbound if they do not have diabetes. All participants will be initiated on an initial dose of 2.5 mg injected subcutaneously in the thigh or abdomen every week on same day and at the same time.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Glucagon-like 1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonist

Also known as: Mounjaro

Tirzepatide

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Stable doses of HF medications within 4 weeks of screening with optimal volume control in the opinion of the investigator.

You may not qualify if:

• 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
• Poorly controlled diabetes (A1c \> 9.5%) OR any type 1 diabetes mellitis
• History of acute or chronic pancreatitis
• Personal or family history of multiple endocrine neoplasia (MEN) or medullary thyroid cancer
• Clinically significant gastric emptying abnormality
• Medical comorbidities that limit survival
• Inability to comply with the study protocol
• Pregnancy

Sponsors & Collaborators

• Columbia University: lead

MeSH Terms

Conditions

Heart Failure, Diastolic; Obesity

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Jessica Idumonyi

CONTACT

212-305-1429; joi2102@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: April 28, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share