Clinical trial NCT02772068: Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a
Official title: Hemodynamic Response to Exercise in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients After Upregulation of SERCA2a
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Heart Failure, Congestive
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2016-05-13
Enrollment: 26
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two separate groups of subjects (senior controls and patients with HFpEF) receiving istaroxime
Primary purpose: BASIC_SCIENCE

Brief summary: Heart failure with preserved ejection fraction or HFpEF, represents nearly 50% of all heart failure cases and is particularly common in the elderly. The disease has no current treatment options. Symptoms typically occur during exertion or exercise and is likely the result of increased cardiac and pulmonary congestion as a result of impaired diastolic function. Istaroxime is a novel activator of SERCA2a, an important regulator of calcium uptake within the myocyte. We will test the hypothesis that Istaroxime will improve diastolic function during exercise in HFpEF patients which in turn will reduce cardiac and pulmonary congestion.

Detailed description: About half of all elderly patients with a diagnosis of congestive heart failure have apparently normal systolic function, so called "heart failure with a preserved ejection fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because of failure to discern key pathophysiologic pathways.

An extensive amount of pre-clinical work has identified that altered sarcoplasmic reticulum (SR) Ca2+ uptake, storage, and release play a major role in the changes in cardiac relaxation associated with aging, especially regarding sequestration of Ca++ by the sarcoplasmic reticular Ca++-ATPase (SERCA2a), which causes cardiac muscle relaxation by reducing cytosolic Ca++. Istaroxime is a relatively new drug that augments lusitropic function by upregulating SERCA2a activity in the heart.

Because of the clear importance of slowed relaxation in HFpEF, and the evidence that depressed SERCA2a activity contributes to the slowed relaxation with aging, the proposed study may be establish the "impairment of SERCA2a" hypothesis as a mechanism of impaired relaxation in HFpEF subjects.

Eligibility criteria: Healthy Senior Controls

Inclusion Criteria:

* age \> 60 years

Exclusion Criteria:

* Coronary Ischemia
* No chronic medical problems
* BMI \> 30 kg/m2

HFpEF Subjects

Inclusion Criteria:

* age \> 60 years
* signs and symptoms of heart failure
* ejection fraction \> 50%
* objective evidence of diastolic dysfunction

Exclusion Criteria:

* Coronary Ischemia
* Chronic Kidney Disease, stage 4 or greater
* Persistent atrial fibrillation
* Severe valvular disease
* BMI \> 45 kg/m2

Primary outcomes:
measure: Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime
timeFrame: Immediate; 90 minutes after infusion
Secondary outcomes:
measure: Change in cardiac relaxation time (isovolumic relaxation time) during exercise with Istaroxime
timeFrame: 90 minutes
Other outcomes:
Locations:
city: Dallas
country: United States
facility: The Institute for Exercise and Environmental Medicine
state: Texas
Study officials:
affiliation: UT Southwestern
name: Benjamin D Levine, MD
role: PRINCIPAL_INVESTIGATOR
References: