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Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in HFpEF (INABLE-Training) (INABLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Mayo Clinic
Sponsor:
Collaborators:
Aires Pharmaceuticals, Inc.
Mast Therapeutics, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Barry Borlaug, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02713126
First received: March 15, 2016
Last updated: September 22, 2016
Last verified: September 2016
  Purpose
Participants with heart failure with preserved ejection fraction will undergo 12 weeks of cardiac rehabilitation for exercise training (ET) and be randomized to either nebulized sodium nitrite inhalation solution or placebo inhalation solution (normal saline) through the training period. Study drug is administered 3 times daily during daytime hours with one of these doses being immediately prior to onset of ET sessions throughout the 12 week trial. The objective is to determine if the inhaled sodium nitrite improves the clinical responses and tolerability of ET.

Condition Intervention Phase
Heart Failure
Drug: Placebo Solution
Drug: Sodium Nitrite Inhalation Solution
Device: Accelerometer
Other: Cardiac Exercise Training
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Inorganic Nitrite to Enhance Benefits From Exercise Training in Heart Failure With Preserved Ejection Fraction

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in exercise capacity [ Time Frame: Baseline, 12 weeks ]
    Change in exercise capacity as measured by peak oxygen consumption


Secondary Outcome Measures:
  • Change in daily activity levels [ Time Frame: Baseline, 12 weeks ]
    Change in daily activity as assessed by accelerometer data; device worn continuously

  • Change in hemodynamics [ Time Frame: Baseline, 12 weeks ]
    Change in hemodynamics and ventricular function measured during echocardiography

  • Change in Quality of Life score [ Time Frame: Baseline, 12 weeks ]
    Change in Quality of Life score, as measured using the Kansas City Cardiomyopathy Questionnaire

  • Change in symptoms of heart failure [ Time Frame: Baseline, 12 weeks ]

Estimated Enrollment: 80
Study Start Date: September 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects will undergo cardiac exercise training and receive inhaled placebo solution three times per day for 12 weeks while wearing an accelerometer
Drug: Placebo Solution
Placebo solution (normal saline), administered by inhalation over 10-15 minutes using a nebulizer, taken every 4 hours or 3 times per day during waking hours for 12 weeks
Other Name: Saline
Device: Accelerometer
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.
Other: Cardiac Exercise Training
Cardiac rehabilitation exercise training consisting of supervised endurance and strength exercise training of approximately one hour, 3 times per week for 12 weeks.
Active Comparator: Sodium Nitrite
Subjects will undergo cardiac exercise training and receive inhaled sodium nitrite inhalation solution three times per day for 12 weeks while wearing an accelerometer
Drug: Sodium Nitrite Inhalation Solution
Sodium Nitrite Inhalation Solution, 80 mg administered by inhalation over 10-15 minutes using a nebulizer, taken every 4 hours or 3 times per day during waking hours for 12 weeks
Other Name: Nitrite, NaNO2
Device: Accelerometer
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.
Other: Cardiac Exercise Training
Cardiac rehabilitation exercise training consisting of supervised endurance and strength exercise training of approximately one hour, 3 times per week for 12 weeks.

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 50 years
  • Symptoms of dyspnea (II-IV) without evidence of a non-cardiac or ischemic explanation for dyspnea
  • Ejection Fraction (EF) ≥ 50%
  • 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
  • Regularly (> 1x per week) swims or does water aerobics
  • Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
  • Inability to comply with planned study procedures
  • Pregnancy or breastfeeding mothers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02713126

Contacts
Contact: Janet M Gatzke, RN 507-538-7177 gatzke.janet@mayo.edu

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Barry A Borlaug, MD         
Sponsors and Collaborators
Barry Borlaug
Aires Pharmaceuticals, Inc.
Mast Therapeutics, Inc.
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Barry A Borlaug, MD Mayo Clinic
  More Information

Responsible Party: Barry Borlaug, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02713126     History of Changes
Other Study ID Numbers: 16-001467
R01HL128526 ( US NIH Grant/Contract Award Number )
Study First Received: March 15, 2016
Last Updated: September 22, 2016
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Pharmaceutical Solutions

ClinicalTrials.gov processed this record on April 28, 2017