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Heart FailurePhase 2INABLENCT02713126

Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training)

A Phase 2 study testing Sodium Nitrite, Accelerometer and Cardiac Exercise Training in people with Heart Failure, run by Barry Borlaug at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Participants with heart failure with preserved ejection fraction will undergo 12 weeks of cardiac rehabilitation for exercise training (ET) and be randomized to either sodium nitrite or placebo through the training period. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Heart Failure
What is being tested?
Sodium Nitrite, Accelerometer and Cardiac Exercise Training
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
92 participants
Where
1 siteUnited States
Study dates
Sep 2016to 12 Apr 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 40 years
  • Symptoms of dyspnea (II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
  • Ejection Fraction (EF) of > or = 50% determined on most recent imaging study within the preceding 5 years, with no change in clinical status suggesting potential for deterioration in systolic function
  • One of the following:
  • Previous hospitalization for Heart Failure (HF) with radiographic evidence (pulmonary venous hypertension, vascular congestion, interstitial edema, pleural effusion) of pulmonary congestion or
  • Catheterization documented elevated filling pressures at rest (Pulmonary Capillary Wedge Pressure (PCWP)= ≥15 or Left Ventricular End-Diastolic Pressure (LVEDP) ≥18) or with exercise (PCWP ≥25) or
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  • Elevated Natruretic Peptide-proBNP (>400 pg/ml) or B-Type Natriuretic Peptide (BNP)(>200 pg/ml) or
  • Echo evidence of diastolic dysfunction/elevated filling pressures manifest by medial E/e' ratio≥15 and/or left atrial enlargement and chronic treatment with a diuretic for signs or symptoms of heart failure
  • Heart failure is primary factor limiting activity as indicated by answering # 2 to the following question:
  • My ability to be active is most limited by:
  • Joint, foot, leg, hip or back pain
  • Shortness of breath and/or fatigue and/or chest pain
  • Unsteadiness or dizziness
  • Lifestyle, weather, or I just don't like to be active
  • No chronic nitrate therapy or not using intermittent sublingual nitroglycerin (requirement for >1 sublingual nitroglycerin per week).
  • No daily use of phosphodiesterase 5 (PDE5) inhibitors or soluble guanylyl cyclase activators and willing to withhold as needed use of PDE5 inhibitors for duration of study
  • Ambulatory (not wheelchair / scooter dependent)
  • Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process.
  • Willingness to wear the accelerometer belt for the duration of the trial

Who cannot join

  • Recent (< 1 month) hospitalization for heart failure
  • Ongoing requirement for PDE5 inhibitor, organic nitrate or soluble guanylyl cyclase activators
  • Hemoglobin (Hgb) < 8.0 g/dl within 30 days prior to randomization
  • Glomerular Filtration Rate (GFR) < 20 ml/min/1.73 m2 within 30 days prior to randomization
  • Systolic blood pressure < 115 mmHg seated or < 90 mmHg standing
  • Resting Heart Rate > 110
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  • Previous adverse reaction to the study drug which necessitated withdrawal of therapy
  • Significant chronic obstructive pulmonary disease that is a primary contributor to symptoms, in the opinion of the Investigator.
  • Ischemia thought to contribute to dyspnea, in the opinion of the Investigator.
  • Documentation of previous Ejection Fraction < 40%
  • Acute coronary syndrome within 3 months defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g., troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
  • Percutaneous Coronary Intervention, coronary artery bypass grafting, or new biventricular pacing within past 3 months
  • Obstructive hypertrophic cardiomyopathy
  • Known infiltrative cardiomyopathy (amyloid)
  • Constrictive pericarditis or tamponade
  • Active myocarditis
  • Complex congenital heart disease
  • Active collagen vascular disease
  • More than mild aortic or mitral stenosis
  • Intrinsic (prolapse, rheumatic) valve disease with more than moderate mitral, tricuspid or aortic regurgitation
  • Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ratio (INR) > 1.7 in the absence of anticoagulation treatment
  • Terminal illness (other than HF) with expected survival of less than 1 year
  • Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
  • Inability to comply with planned study procedures
  • Pregnancy or breastfeeding mothers

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF)

Participants with heart failure with preserved ejection fraction will undergo 12 weeks of cardiac rehabilitation for exercise training (ET) and be randomized to either sodium nitrite or placebo through the training period. Study drug is administered 3 times daily with one of these doses being 30 minutes prior to onset of ET sessions throughout the12 week trial. The objective is to determine if the sodium nitrite improves the clinical responses and tolerability of ET.

Conditions
Heart Failure
Being tested
Placebo, Sodium Nitrite, Accelerometer, Cardiac Exercise Training
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    administered orally or inhaled, taken every 4 hours or 3 times per day during waking hours for 12 weeks

  • Sodium NitriteDrug

    Also called Nitrite

    administered orally or inhaled, 40 mg, taken every 4 hours or 3 times per day during waking hours for 12 weeks

  • AccelerometerDevice

    External triaxial accelerometer is worn externally at the hip during exercise training sessions, and day/night to continuously measure activity levels, removed for bathing only.

  • Cardiac Exercise TrainingOther

    Cardiac rehabilitation exercise training consisting of supervised endurance and strength exercise training of approximately one hour, 3 times per week for 12 weeks.

Study groups in NCT02713126
Study groupRoleWhat they receive
PlaceboPlacebo comparatorSubjects will undergo cardiac exercise training and receive inhaled or oral placebo three times per day for 12 weeks while wearing an accelerometer
Receives: Drug: Placebo; Device: Accelerometer; Other: Cardiac Exercise Training
Sodium NitriteActive comparatorSubjects will undergo cardiac exercise training and receive inhaled or oral sodium nitrite three times per day for 12 weeks while wearing an accelerometer
Receives: Drug: Sodium Nitrite; Device: Accelerometer; Other: Cardiac Exercise Training

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Peak Rate of Oxygen (VO2)

    Exercise capacity as measured by the peak rate of oxygen (VO2) consumption achieved during exercising testing. Peak VO2 is expressed as milliliters of oxygen per kilogram of body mass per minute.

    Measured: Baseline, 12 weeks

Secondary outcomes (4)

  1. Change in Daily Activity Levels

    The change in daily activity levels as assessed by accelerometer data and reported as average accelerometry units.

    Measured: Baseline, 12 weeks

  2. Change in Cardiac Hemodynamics

    The change in cardiac hemodynamics as measured by echocardiography. The E/e' ratio is a marker used to evaluate the left ventricular (LV) filling pressures during exercise. An E/e' ratio of <8 is considered to be normal, a ratio >15 is considered to reflect an increase in the LV filling pressure.

    Measured: Baseline, 12 weeks

  3. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score

    The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a self-administered questionnaire that provides a measure of symptoms and physical limitations associated with heart failure. The overall summary score ranges from 0-100, where the higher the score the better the health status.

    Measured: Baseline, 12 weeks

  4. Change in Six Minute Walk Test

    The six minute walk test is an exercise test used to assess aerobic capacity and endurance. The total distance covered over six minutes is measured in meters.

    Measured: Baseline, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2016 (estimated)
  2. Study startSep 2016
  3. Primary completion12 Apr 2022
  4. Study completion12 Apr 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02713126
Sponsor's protocol ID
16-001467
Other IDs
R01HL128526
Acronym
INABLE
Status last verified
Apr 2023
First submitted
15 Mar 2016
Last updated
26 Apr 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Borlaug BA, Koepp KE, Reddy YNV, Obokata M, Sorimachi H, Freund M, Haberman D, Sweere K, Weber KL, Overholt EA, Safe BA, Omote K, Omar M, Popovic D, Acker NG, Gladwin MT, Olson TP, Carter RE. Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction: The INABLE-Training Trial. Mayo Clin Proc. 2024 Feb;99(2):206-217. doi: 10.1016/j.mayocp.2023.08.031. Epub 2023 Dec 21.

    PubMed 38127015

  • Alogna A, Koepp KE, Sabbah M, Espindola Netto JM, Jensen MD, Kirkland JL, Lam CSP, Obokata M, Petrie MC, Ridker PM, Sorimachi H, Tchkonia T, Voors A, Redfield MM, Borlaug BA. Interleukin-6 in Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2023 Nov;11(11):1549-1561. doi: 10.1016/j.jchf.2023.06.031. Epub 2023 Aug 9.

    PubMed 37565977

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sodium Nitrite, Accelerometer and Cardiac Exercise Training in people with Heart Failure, run by Barry Borlaug 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 19 inclusion and 25 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 26 Apr 2023. 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. Some participants in this study may receive a placebo. 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Peak Rate of Oxygen (VO2) (time frame: Baseline, 12 weeks). 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 NCT02713126, which also lists 2 linked publications.

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 26 Apr 2023.

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