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| ID | Type | Description | Link |
|---|---|---|---|
| 1R56AG051637-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This is a randomized double blinded controlled trial of 20-40 mg sodium nitrite tid in subjects with HFpEF. Primary outcomes are measures of physical function with non-invasive and invasive cardiopulmonary exercise testing, and fatigability, skeletal muscle bioenergetics, serology including inflammatory markers and platelet bioenergetics, quality of life measures.
Age-related physiological changes predispose to heart failure with preserved ejection fraction (HFpEF). Thus, HFpEF prevalence is escalating as the older population expands. High mortality and morbidity, diminished quality of life, and spiraling healthcare costs are typical consequences, and no effective HFpEF therapy is known. Therefore, several small exercise training (ExT) trials for HFpEF stand out by showing that ExT result in improved aerobic exercise capacity and infer that ExT constitutes novel substantive therapy. Nonetheless, such benefit was evident only after months of moderate to high intensity ExT; regimens that are unfeasible for most patients. In fact, poor compliance with ExT is typical in most HFpEF patients. The investigators propose there are intrinsic physiological components of HFpEF pathophysiology that predispose to "fatigability". The investigators advance the concept of fatigability by quantifying it as a performance-based measure; i.e., subjective tiring during a standardized steady-state walking (perceived fatigability) and deterioration of self-selected walking speed over time (performance fatigability). The investigators assert that therapies to reduce fatigability will enhance HFpEF outcomes. Ongoing studies reveal pleiotropic benefits of oral inorganic nitrite (NO2), including enhanced performance of skeletal muscle (metabolism and bioenergetics) and vasomotor responses (systemic and pulmonary). The investigators' pilot work shows safety and biological efficacy of oral NO2 capsules. Thus, the investigators propose a randomized, controlled, double-blinded trial to study oral NO2 therapy in older (≥70 years) HFpEF patients. Aim 1 explores the utility of NO2 capsules to reduce perceived and performance fatigability (rated perceived exertion), improve aerobic capacity (peak oxygen uptake) and increase daily activity (accelerometry). Aim 2 delineates the mediating processes by which NO2 benefits are achieved. Skeletal muscle determinants are differentiated from the right and left heart vasomotor dynamics by integrating assessments using 31Phosphorus magnetic resonance spectroscopy and percutaneous needle muscle biopsies with those made using non-invasive and invasive cardiopulmonary exercise testing, near infrared spectroscopy and other techniques. The principal investigator is trained geriatrics and cardiology, and is solidly oriented to the dynamics of aging and cardiovascular disease (clinically and mechanistically) with particular expertise in functional assessment and skeletal muscle gene expression as determinants of performance. The investigative team provides formidable synergies that are well-suited to this translational investigation of systemic, cellular, and sub-cellular physiological dynamics. Our proposal is significant in multiple respects: 1) HFpEF is endemic with aging and constitutes a critical contemporary healthcare challenge today's growing population of older adults. 2) Fatigability is rooted in HFpEF pathophysiology, but it has not previously been addressed as a key part of management. 3) NO2 therapy is a novel and compelling therapeutic strategy. 4) Mechanisms underlying fatigability are clarified; we advance principles of patient-centered care by clarifying mechanisms that underlie a patient's experience of fatigability.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental | 20 or 40 mg sodium nitrite tid |
|
| Control | Placebo Comparator | 20 or 40 mg placebo tid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sodium nitrite | Drug | Subjects to receive active study drug three times daily during treatment period and then post treatment testing period. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cardiorespiratory Fitness | Assessment of peak Oxygen uptake (VO2) maximum via symptom limited exercise testing | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Perceived Fatigability | Assessment of Rate of Perceived Exertion (RPE) during steady state exercise testing at the last minute of the test. The RPE scale (Rate of Perceived Exertion) goes from 6-20 with a higher number indicating more effort and possibly a worse outcome. | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Adiponectin | Change in adiponectin | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks |
| Blood Nitrate | Change in blood levels to assess efficacy of study drug |
Inclusion Criteria:
Age ≥70 years
Diagnosis of HFpEF [adapted from the 2016 European Society of Cardiology (ESC) Guidelines to include:
1. Prior diagnosis of HF via one of these:
medical record diagnosis by attending cardiologist
verbal confirmation of HFpEF with attending cardiologist
PI review of medical record to confirm HFpEF AND 2. Ejection Fraction % ≥40
Clinically stable (euvolemic; baseline heart rate <100 bpm) and without hospitalization or invasive cardiac procedure for 6 weeks
Patients using 81 milligram (mg) aspirin (ASA) will be eligible, but will be asked to hold the medication for 3 days prior to biopsy. This technique has previously been used with consistent safety. Patients will also be asked to avoid non-steroidal anti-inflammatory medications (NSAIDs) for 2 days prior to the biopsy.
Patients using anti-thrombin and anti-platelet therapy will plan to modify prior to muscle biopsies individually in coordination with the participant's primary cardiologist.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel E Forman, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Montefiore Hospital | Pittsburgh | Pennsylvania | 15213 | United States |
De-identified data may be shared with other future investigators as research questions arise.
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A limit in time frame for sharing has not been defined.
Only de-identified data approved for sharing by the PI.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sodium Nitrite | 20 or 40 mg sodium nitrite tid sodium nitrite: Subjects to receive active study drug three times daily during treatment period and then post treatment testing period. |
| FG001 | Placebo | 20 or 40 mg placebo tid Control: Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sodium Nitrite | 20 or 40 mg sodium nitrite tid sodium nitrite: Subjects to receive active study drug three times daily during treatment period and then post treatment testing period. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cardiorespiratory Fitness | Assessment of peak Oxygen uptake (VO2) maximum via symptom limited exercise testing | In the treatment arm, a subject withdrew after pre-treatment testing. 1 subject from the control arm withdrew after randomization but before testing. A second withdrew prior after pre-treatment testing, but before post-treatment testing. | Posted | Mean | Standard Deviation | ml/kg/min | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
|
Adverse event data was collected for the entire 16 weeks the subject was in the study via telephone assessment for interval histories from visits 1-7 and 7 days after visit 7.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment Arm | 20 or 40 mg sodium nitrite tid sodium nitrite: Subjects to receive active study drug three times daily during treatment period and then post treatment testing period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Low diastolic blood pressure | Cardiac disorders | Non-systematic Assessment | DBP 58-59 during pharmacokinetic testing, asymptomatic |
Magnetic Resonance Spectroscopy, Oroboros, and invasive CPET equipment unexpectedly had limited availability.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tara Sheila Stakich | University of Pittsburgh | 412-864-2082 | tss54@pitt.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 9, 2018 | Nov 26, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D012977 | Sodium Nitrite |
| D009573 | Nitrites |
| ID | Term |
|---|---|
| D009608 | Nitrous Acid |
| D017672 | Nitrogen Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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| Control | Drug | Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period. |
|
|
| Bioenergetics: In-Vivo 31P MRS Respirations |
Phosphocreatine reuptake after exercise during the kicking exercise in the 31P MRS (magnetic resonance spectroscopy) |
| Week 3 (pre drug) to week 10(post drug); approx. 8 weeks |
| Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis | Mitochondrial respiration was analyzed by assessing O2 consumption by skeletal muscle mitochondria at Energetic State 3.1 using the Oroboros instrument. This state is generally used a marker for mitochondrial efficiency. Increases in consumption are generally linked to a better outcome. | Week 5 (pre-drug) to week 16 (post-drug); approx. 8 weeks |
| Exercise-induced Changes in Pulmonary Arterial Pressure | Pulmonary arterial pressure, an indication of cardiopulmonary hemodynamics and cardiac function, was measured at rest and at peak exercise during an invasive cardiopulmonary exercise test. | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
| Exercise-induced Changes in Pulmonary Capillary Wedge Pressure | Pulmonary capillary wedge pressure, an indication of cardiopulmonary hemodynamics and cardiac function, was measured at rest and at peak exercise during an invasive cardiopulmonary exercise test. | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
| Patients With Pulmonary Hypertension | Right Ventricular-Pulmonary Artery Coupling, assessed by right ventricular ejection fraction (RVEF) and pulmonary artery systolic pressure (PASP), decreases with worsening right heart failure. We will be measuring this by assessing RVEF and PASP during invasive cardiopulmonary exercise testing in patients that meet criteria for pulmonary hypertension. | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
| Steps From Accelerometry Assessment of Daily Activity | Actigraph device-specific activity steps on daily-wear wrist device based on movement. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Sedentary Events From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Sedentary bout is a triggered stint of time that the patient is not moving or has low level of activity sensed by the accelerometer. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Light Activity Duration From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Light activity is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Moderate to Vigorous Physical Activity From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. MVPA is Moderate-to-vigorous physical activity that is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Vector Magnitude Counts From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Vector Magnitude in counts per day are accelerations in 3 dimensions that indicate activity. More counts is associated with more activity. More counts in a shorter duration of time indicate light, moderate, and vigorous activity. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Sedentary Event Duration From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Sedentary bout is a triggered stint of time that the patient is not moving or has low level of activity sensed by the accelerometer. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Light Activity Events Percentage of Day From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Light activity is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Moderate to Vigorous Physical Activity Percentage From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. MVPA is Moderate-to-vigorous physical activity that is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
| Week 5 (pre drug) to week 16 (post drug); approx. 8 week |
| Brain Natriuretic Protein | Change in brain natriuretic protein (BNP) | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks |
| Cardiopulmonary Exercise Testing: iCPET | Invasive cardiopulmonary exercise testing | Week 3 (pre-drug) to week 10 (post drug); approx. 8 weeks |
| Cardiopulmonary Exercise Testing; nCPET | Non-invasive cardiopulmonary exercise testing | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Cognitive Function | Change in pre and post scores on the Montreal Cognitive Assessment | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Co-morbid Illness | Change in pre and post scores on the Charlson Comorbidity Index | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Co-morbidity Medications | Medications for comorbidity managment | Week 1 pre drug to week 16 post drug |
| Echocardiogram | Change in cardiac strain | Week 1 pre-drug to week 16 post drug |
| Fatigability | Change in pre and post scores on the Pittsburgh Fatigability Index | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Frailty Index Assessment | Physician assessment of frailty using the Canadian Clinical Frailty Scale | Week 1 screening pre-drug to week 16 post drug |
| Gene Expression | Change in DNA from Polymerase Chain Reaction analysis | Week 5 (pre drug) to week 16 (post drug); approx. 8 week |
| Glomerular Filtration Rate | Change in glomerular filtration rate (GFR) | Week 5 (pre drug) to week 16 (post drug); approx. 8 week |
| Glycosylated Hemoglobin | Change in glycosylated hemoglobin (HgbA1c) | Week 5 (pre drug) to week 16 (post drug); approx. 8 week |
| Hematocrit | Change in hematocrit | Week 1 pre drug to week 16 post drug |
| Hemoglobin | Change in hemoglobin | Week 1 pre drug to week 16 post drug |
| Hemodynamics; Blood Pressure | Change in Blood pressure | Week 1 pre drug to week 16 post drug |
| Hemodynamics; Heart Rate | Change in heart rate | Week 1 pre drug to week 16 post drug |
| Muscle Protein | Change in protein content of muscle fiber | Week 5 (pre drug) to week 16 (post drug); approx. 8 week |
| Near Infrared Spectroscopy | Assessment of blood flow during exercise | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Pain | Change in pre and post scores on the McGill Pain Questionnaire | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Physical Frailty and Balance | Change in score on Standard Physical Performance Battery at visit 2 pre drug and visit 5 | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Physical Activity | Change in pre and post scores on the CHAMPS (Community Healthy Activities Program for Seniors) Activities Questionnaire for Older Adults-physical activity | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Quality of Life | Change in pre and post scores on the Kansas City Cardiomyopathy Questionnaire subject self reported responses | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Submaximal Exercise Performance | Change in distance on six minute walk test | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Self-efficacy | Change in pre and post scores on the Sullivan Cardiac Self Efficacy questionnaire | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
| Thyroid Stimulating Hormone | Change in thyroid stimulating hormone (TSH) | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks |
| Lost to Follow-up |
|
20 or 40 mg placebo tid
Control: Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Ejection Fraction | Mean | Standard Deviation | Percentage of blood |
|
20 or 40 mg placebo tid
Control: Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period.
|
|
| Secondary | Perceived Fatigability | Assessment of Rate of Perceived Exertion (RPE) during steady state exercise testing at the last minute of the test. The RPE scale (Rate of Perceived Exertion) goes from 6-20 with a higher number indicating more effort and possibly a worse outcome. | In the treatment arm, a subject withdrew after pre-treatment testing. 1 subject from the control arm withdrew after randomization but before testing. A second withdrew prior after pre-treatment testing, but before post-treatment testing. | Posted | Mean | Standard Deviation | Units on a scale | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks |
|
|
|
| Secondary | Bioenergetics: In-Vivo 31P MRS Respirations | Phosphocreatine reuptake after exercise during the kicking exercise in the 31P MRS (magnetic resonance spectroscopy) | Magnetic resonance spectroscopy equipment had unexpected limited availability, which is why so few participants were analyzed. | Posted | Mean | Standard Deviation | 1/s | Week 3 (pre drug) to week 10(post drug); approx. 8 weeks |
|
|
|
| Secondary | Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis | Mitochondrial respiration was analyzed by assessing O2 consumption by skeletal muscle mitochondria at Energetic State 3.1 using the Oroboros instrument. This state is generally used a marker for mitochondrial efficiency. Increases in consumption are generally linked to a better outcome. | Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability. | Posted | Mean | Standard Deviation | pmol/(s*mg) | Week 5 (pre-drug) to week 16 (post-drug); approx. 8 weeks |
|
|
|
| Secondary | Exercise-induced Changes in Pulmonary Arterial Pressure | Pulmonary arterial pressure, an indication of cardiopulmonary hemodynamics and cardiac function, was measured at rest and at peak exercise during an invasive cardiopulmonary exercise test. | Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability. | Posted | Mean | Standard Deviation | mmHg | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
|
|
|
| Secondary | Exercise-induced Changes in Pulmonary Capillary Wedge Pressure | Pulmonary capillary wedge pressure, an indication of cardiopulmonary hemodynamics and cardiac function, was measured at rest and at peak exercise during an invasive cardiopulmonary exercise test. | Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability. | Posted | Mean | Standard Deviation | mmHg | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
|
|
|
| Secondary | Patients With Pulmonary Hypertension | Right Ventricular-Pulmonary Artery Coupling, assessed by right ventricular ejection fraction (RVEF) and pulmonary artery systolic pressure (PASP), decreases with worsening right heart failure. We will be measuring this by assessing RVEF and PASP during invasive cardiopulmonary exercise testing in patients that meet criteria for pulmonary hypertension. | Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability. | Posted | Count of Participants | Participants | Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks |
|
|
|
| Secondary | Steps From Accelerometry Assessment of Daily Activity | Actigraph device-specific activity steps on daily-wear wrist device based on movement. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | Counts/day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Sedentary Events From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Sedentary bout is a triggered stint of time that the patient is not moving or has low level of activity sensed by the accelerometer. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | bouts/day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Light Activity Duration From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Light activity is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | seconds/day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Moderate to Vigorous Physical Activity From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. MVPA is Moderate-to-vigorous physical activity that is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | minutes/day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Vector Magnitude Counts From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Vector Magnitude in counts per day are accelerations in 3 dimensions that indicate activity. More counts is associated with more activity. More counts in a shorter duration of time indicate light, moderate, and vigorous activity. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | Counts/day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Other Pre-specified | Adiponectin | Change in adiponectin | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Blood Nitrate | Change in blood levels to assess efficacy of study drug | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 week | Participants |
| Other Pre-specified | Brain Natriuretic Protein | Change in brain natriuretic protein (BNP) | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Cardiopulmonary Exercise Testing: iCPET | Invasive cardiopulmonary exercise testing | Not Posted | Week 3 (pre-drug) to week 10 (post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Cardiopulmonary Exercise Testing; nCPET | Non-invasive cardiopulmonary exercise testing | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Cognitive Function | Change in pre and post scores on the Montreal Cognitive Assessment | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Co-morbid Illness | Change in pre and post scores on the Charlson Comorbidity Index | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Co-morbidity Medications | Medications for comorbidity managment | Not Posted | Week 1 pre drug to week 16 post drug | Participants |
| Other Pre-specified | Echocardiogram | Change in cardiac strain | Not Posted | Week 1 pre-drug to week 16 post drug | Participants |
| Other Pre-specified | Fatigability | Change in pre and post scores on the Pittsburgh Fatigability Index | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Frailty Index Assessment | Physician assessment of frailty using the Canadian Clinical Frailty Scale | Not Posted | Week 1 screening pre-drug to week 16 post drug | Participants |
| Other Pre-specified | Gene Expression | Change in DNA from Polymerase Chain Reaction analysis | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 week | Participants |
| Other Pre-specified | Glomerular Filtration Rate | Change in glomerular filtration rate (GFR) | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 week | Participants |
| Other Pre-specified | Glycosylated Hemoglobin | Change in glycosylated hemoglobin (HgbA1c) | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 week | Participants |
| Other Pre-specified | Hematocrit | Change in hematocrit | Not Posted | Week 1 pre drug to week 16 post drug | Participants |
| Other Pre-specified | Hemoglobin | Change in hemoglobin | Not Posted | Week 1 pre drug to week 16 post drug | Participants |
| Other Pre-specified | Hemodynamics; Blood Pressure | Change in Blood pressure | Not Posted | Week 1 pre drug to week 16 post drug | Participants |
| Other Pre-specified | Hemodynamics; Heart Rate | Change in heart rate | Not Posted | Week 1 pre drug to week 16 post drug | Participants |
| Other Pre-specified | Muscle Protein | Change in protein content of muscle fiber | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 week | Participants |
| Other Pre-specified | Near Infrared Spectroscopy | Assessment of blood flow during exercise | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Pain | Change in pre and post scores on the McGill Pain Questionnaire | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Physical Frailty and Balance | Change in score on Standard Physical Performance Battery at visit 2 pre drug and visit 5 | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Physical Activity | Change in pre and post scores on the CHAMPS (Community Healthy Activities Program for Seniors) Activities Questionnaire for Older Adults-physical activity | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Quality of Life | Change in pre and post scores on the Kansas City Cardiomyopathy Questionnaire subject self reported responses | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Submaximal Exercise Performance | Change in distance on six minute walk test | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Self-efficacy | Change in pre and post scores on the Sullivan Cardiac Self Efficacy questionnaire | Not Posted | Week 2(pre drug) to Week 10( post drug); approx. 8 weeks | Participants |
| Other Pre-specified | Thyroid Stimulating Hormone | Change in thyroid stimulating hormone (TSH) | Not Posted | Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks | Participants |
| Secondary | Sedentary Event Duration From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Sedentary bout is a triggered stint of time that the patient is not moving or has low level of activity sensed by the accelerometer. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | minutes/bout | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Light Activity Events Percentage of Day From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. Light activity is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | % of day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| Secondary | Moderate to Vigorous Physical Activity Percentage From Accelerometry Assessment of Daily Activity | Assessment of daily activity using accelerometry on a daily-wear wrist device. MVPA is Moderate-to-vigorous physical activity that is a triggered stint of time that the patient has a slightly elevated amount of activity based on biometrics such as movement and heart rate. | Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed. | Posted | Mean | Standard Deviation | Percentage of day | Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 3 |
| 7 |
| EG001 | Control Arm | 20 or 40 mg placebo tid Control: Subjects randomized to placebo to receive three times daily during treatment period and then post treatment testing period. | 0 | 8 | 0 | 8 | 7 | 8 |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment | Took bicosadyl with relief |
|
| Palpitations | Cardiac disorders | Non-systematic Assessment |
|
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Hematoma | Blood and lymphatic system disorders | Non-systematic Assessment | Small, at wrist for iCPET (not all subjects in either arm at risk) |
|
| Subconjunctival Hemorrhage | Eye disorders | Non-systematic Assessment | Asymptomatic, and 100% clear |
|
| Bradycardia | Cardiac disorders | Non-systematic Assessment | Beta blocker dose was adjusted prior to administration of study drug/placebo |
|
| Chest pain | Gastrointestinal disorders | Non-systematic Assessment | Cardiologist advised likely GI in origin, resolved with OTC antacid |
|
| Pain at Biopsy site | Injury, poisoning and procedural complications | Non-systematic Assessment | Greater than usual. Brief episode. Resolved spontaneously without issue. |
|
| Swelling of cheeks | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Leg Cramping | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dry Mouth | General disorders | Non-systematic Assessment |
|
| Backache | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Upper respiratory infection-like symptoms | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Difficulty Urinating | Renal and urinary disorders | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | Non-systematic Assessment |
|
| Unable to afford daily medications | Social circumstances | Non-systematic Assessment |
|
| Took investigational drug/placebo early | Investigations | Non-systematic Assessment |
|
Not provided
Not provided
| D000838 |
| Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D009930 | Organic Chemicals |
| RPE during last minute of the test, Post-treatment |
|
|
| RPE during last minute of the test, Change |
|
|
| O2 Consumption, Overall change |
|
| mPAP at Peak Exercise, Pre-treatment |
|
| mPAP at Peak Exercise, Post-treatment |
|
| PCWP at Peak Exercise, Pre-treatment |
|
| PCWP at Peak Exercise, Post-treatment |
|
| Steps, Change |
|
| # of sedentary bouts/day, Change |
|
| Light activity (sec/day), Change |
|
| MVPA, Change |
|
| Vector Magnitude, Change |
|
| Average Sedentary Bout Duration, Chg |
|
| % in Light Activity,Change |
|
| % in MVPA, Change |
|