Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a

Heart Failure, Congestive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02772068
• Other study ID #: STU 042013-039
• Secondary ID: R01AG017479
• Status: Completed
• Phase: Early Phase 1
• Start date: September 15, 2015
• Est. completion date: December 1, 2018

Study information

• Verified date: June 2022
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 1, 2018
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Congestive

Intervention

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

Other:
• Exercise

Locations

Country	Name	City	State
United States	The Institute for Exercise and Environmental Medicine	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Benjamin Levine	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime	Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime	Immediate; 90 minutes after infusion
Secondary	Change in cardiac relaxation time (isovolumic relaxation time) during exercise with Istaroxime	Change in cardiac relaxation time (isovolumic relaxation time) during exercise	90 minutes