Heart Failure, CongestiveEarly Phase 1NCT02772068
Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a
A Early Phase 1 study testing Istaroxime and Exercise in people with Heart Failure, Congestive, run by Benjamin Levine at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 60 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Congestive
- What is being tested?
- Istaroxime and Exercise
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2015to 1 Dec 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age > 60 years
- age > 60 years
- signs and symptoms of heart failure
- ejection fraction > 50%
- objective evidence of diastolic dysfunction
Who cannot join
- Coronary Ischemia
- No chronic medical problems
- BMI > 30 kg/m2
- HFpEF Subjects
- Coronary Ischemia
- Chronic Kidney Disease, stage 4 or greater
Show all 9Show fewer
- Persistent atrial fibrillation
- Severe valvular disease
- BMI > 45 kg/m2
Trial locations and contacts
1 site in 1 country.
United States1 site
The Institute for Exercise and Environmental Medicine
Dallas, Texas, 75231
About this study
Official title: 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.
Read the 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.
- Conditions
- Heart Failure, Congestive
- Being tested
- Istaroxime, Exercise
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IstaroximeDrug
Also called exercise
Subjects will be given Istaroxime, a novel SERCA2a activator one hour prior and during exercise.
ExerciseOther
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Istaroxime; Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Immediate; 90 minutes after infusion
Secondary outcomes (1)
Change in cardiac relaxation time (isovolumic relaxation time) during exercise with Istaroxime
Change in cardiac relaxation time (isovolumic relaxation time) during exercise
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study start15 Sep 2015
- Primary completion1 Dec 2018
- Study completion1 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, CongestiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Two separate groups of subjects (senior controls and patients with HFpEF) receiving istaroxime
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Benjamin Levine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Benjamin Levine, University of Texas Southwestern Medical Center
- Investigators
- Benjamin D Levine, MD, Principal investigator, UT Southwestern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02772068
- Sponsor's protocol ID
- STU 042013-039
- Other IDs
- R01AG017479
- Status last verified
- Jun 2022
- First submitted
- 11 May 2016
- Last updated
- 29 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37086245
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hemodynamic Response to Exercise in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients After Upregulation of SERCA2a
- ClinicalTrials.gov ID
- NCT02772068
- Acronym / sponsor ID
- STU 042013-039
- Conditions
- Heart Failure, Congestive
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Benjamin LevineUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 15 Sep 2015 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 13 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Two separate groups of subjects (senior controls and patients with HFpEF) receiving istaroxime
| Arm | Type | Receives |
|---|---|---|
| Healthy Senior Control | Active comparator | Drug: Istaroxime, Other: ExerciseFifteen 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. |
| Heart failure patients | Experimental | Drug: Istaroxime, Other: ExerciseFifteen 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. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age > 60 years
- age > 60 years
- signs and symptoms of heart failure
- ejection fraction > 50%
- objective evidence of diastolic dysfunction
Key exclusion criteria (9 listed)
- Coronary Ischemia
- No chronic medical problems
- BMI > 30 kg/m2
- HFpEF Subjects
- Coronary Ischemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IstaroximeAlso: exerciseSubjects will be given Istaroxime, a novel SERCA2a activator one hour prior and during exercise. | Drug | Healthy Senior Control, Heart failure patients |
| Exercise | Other | Healthy Senior Control, Heart failure patients |
Primary outcome
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
1 secondary outcome
Change in cardiac relaxation time (isovolumic relaxation time) during exercise with Istaroxime
Time frame: 90 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2022.
- Derived from this study: PubMed 37086245Sarma 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin D Levine, MD principal investigator
UT Southwestern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Istaroxime and Exercise in people with Heart Failure, Congestive, run by Benjamin Levine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cardiac filling pressures (pulmonary capillary wedge pressure) during exercise with Istaroxime (time frame: Immediate; 90 minutes after infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02772068, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2022.