Skip to main content
OpenTrials
Completed

NCT Number: NCT02772068

Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Heart Failure, Congestive Cardiovascular Diseases Heart Diseases Heart Failure

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

The Institute for Exercise and Environmental Medicine

Dallas, Texas, 75231, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

istaroxime

Drug

Subjects will be given Istaroxime, a novel SERCA2a activator one hour prior and during exercise.

Other names: exercise

Exercise

Other

Primary outcomes

  1. Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime

    Time frame: Immediate; 90 minutes after infusion

    Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime

Secondary outcomes

  1. Change in cardiac relaxation time (isovolumic relaxation time) during exercise with Istaroxime

    Time frame: 90 minutes

    Change in cardiac relaxation time (isovolumic relaxation time) during exercise

Sponsors and collaborators

Lead sponsor

Benjamin Levine

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Official study title

Hemodynamic Response to Exercise in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients After Upregulation of SERCA2a

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
May 13, 2016
Registry last updated
Jun 29, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.