search
Back to results

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

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
Sodium Nitrite
Accelerometer
Cardiac Exercise Training
Sponsored by
Barry Borlaug
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
    • 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:

  1. Joint, foot, leg, hip or back pain
  2. Shortness of breath and/or fatigue and/or chest pain
  3. Unsteadiness or dizziness

  4. 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

Exclusion Criteria:

  • 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
  • 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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Sodium Nitrite

Arm Description

Subjects will undergo cardiac exercise training and receive inhaled or oral placebo three times per day for 12 weeks while wearing an accelerometer

Subjects will undergo cardiac exercise training and receive inhaled or oral sodium nitrite three times per day for 12 weeks while wearing an accelerometer

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
March 15, 2016
Last Updated
April 3, 2023
Sponsor
Barry Borlaug
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02713126
Brief Title
Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF) (INABLE-Training)
Acronym
INABLE
Official Title
Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction (HFpEF)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 2016 (undefined)
Primary Completion Date
April 12, 2022 (Actual)
Study Completion Date
April 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Barry Borlaug
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
92 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will undergo cardiac exercise training and receive inhaled or oral placebo three times per day for 12 weeks while wearing an accelerometer
Arm Title
Sodium Nitrite
Arm Type
Active Comparator
Arm Description
Subjects will undergo cardiac exercise training and receive inhaled or oral sodium nitrite three times per day for 12 weeks while wearing an accelerometer
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
administered orally or inhaled, taken every 4 hours or 3 times per day during waking hours for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Sodium Nitrite
Other Intervention Name(s)
Nitrite
Intervention Description
administered orally or inhaled, 40 mg, taken every 4 hours or 3 times per day during waking hours for 12 weeks
Intervention Type
Device
Intervention Name(s)
Accelerometer
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Cardiac Exercise Training
Intervention Description
Cardiac rehabilitation exercise training consisting of supervised endurance and strength exercise training of approximately one hour, 3 times per week for 12 weeks.
Primary Outcome Measure Information:
Title
Change in Peak Rate of Oxygen (VO2)
Description
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.
Time Frame
Baseline, 12 weeks
Secondary Outcome Measure Information:
Title
Change in Daily Activity Levels
Description
The change in daily activity levels as assessed by accelerometer data and reported as average accelerometry units.
Time Frame
Baseline, 12 weeks
Title
Change in Cardiac Hemodynamics
Description
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.
Time Frame
Baseline, 12 weeks
Title
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Description
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.
Time Frame
Baseline, 12 weeks
Title
Change in Six Minute Walk Test
Description
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.
Time Frame
Baseline, 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry A Borlaug, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

We'll reach out to this number within 24 hrs