Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a

June 22, 2022 updated by: Benjamin Levine

Hemodynamic Response to Exercise in Heart Failure With Preserved Ejection Fraction (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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75231
        • The Institute for Exercise and Environmental Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

60 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Healthy Senior Control
Fifteen healthy senior subjects will perform light exercise at a fixed heart rate of 100 beats per minute. Subjects will then be given either placebo infusion (normal saline) or Istaroxime infusion for one hour. Subjects will be blinded to which infusion they are receiving. Subjects will then repeat light exercise at a fixed heart rate of 100 beats per minute. Primary outcome is changes in cardiac filling pressures during exercise.
Other: Exercise
Drug: Istaroxime
Subjects will be given Istaroxime, a novel SERCA2a activator one hour prior and during exercise.
Other Names:
  • exercise
EXPERIMENTAL: Heart failure patients
Fifteen HFpEF subjects will perform light exercise at a fixed heart rate of 100 beats per minute. Subjects will then be given either placebo infusion (normal saline) or Istaroxime infusion for one hour. Subjects will be blinded to which infusion they are receiving. Subjects will then repeat light exercise at a fixed heart rate of 100 beats per minute. Primary outcome is changes in cardiac filling pressures during exercise.
Other: Exercise
Drug: Istaroxime
Subjects will be given Istaroxime, a novel SERCA2a activator one hour prior and during exercise.
Other Names:
  • exercise

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Immediate; 90 minutes after infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
90 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Benjamin Levine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Benjamin D Levine, MD, UT Southwestern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 11, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 13, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU 042013-039
  • R01AG017479 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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