Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a

NCT02772068 | Completed Early Phase 1 DMC

• 2 other identifiers: STU 042013-039R01AG017479
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure, Congestive

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  90 minutes

Study Arms (2)

Healthy Senior Control

ACTIVE COMPARATOR

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.

Drug: Istaroxime; Other: Exercise

Heart failure patients

EXPERIMENTAL

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.

Drug: Istaroxime; Other: Exercise

Interventions

Istaroxime DRUG

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

Also known as: exercise

Healthy Senior Control; Heart failure patients

Exercise OTHER

Healthy Senior Control; Heart failure patients

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age \> 60 years

You may not qualify if:

• Coronary Ischemia
• No chronic medical problems
• BMI \> 30 kg/m2
• HFpEF Subjects
• age \> 60 years
• signs and symptoms of heart failure
• ejection fraction \> 50%
• objective evidence of diastolic dysfunction
• Coronary Ischemia
• Chronic Kidney Disease, stage 4 or greater
• Persistent atrial fibrillation
• Severe valvular disease
• BMI \> 45 kg/m2

Sponsors & Collaborators

• Benjamin Levine: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

The Institute for Exercise and Environmental Medicine

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• Sarma S, MacNamara JP, Hieda M, Howden EJ, Lawley JS, Livingston S, Samels M, Levine BD. SERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2023 Jul;11(7):760-771. doi: 10.1016/j.jchf.2023.02.006. Epub 2023 Apr 19.

  PMID: 37086245 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Istaroxime; Exercise

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Benjamin D Levine, MD

  UT Southwestern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Two separate groups of subjects (senior controls and patients with HFpEF) receiving istaroxime

Study Record Dates

• First Submitted: May 11, 2016
• First Posted: May 13, 2016
• Study Start: September 15, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: June 29, 2022

Record last verified: 2022-06

Locations

US (1)