Trial Outcomes & Findings for Oral Nitrite for Older Heart Failure With Preserved Ejection Fraction (NCT NCT02918552)

NCT ID: NCT02918552

Last Updated: 2020-01-22

Results Overview

Assessment of peak Oxygen uptake (VO2) maximum via symptom limited exercise testing

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 15 participants
• Primary outcome timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks
• Results posted on: 2020-01-22

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	7	8
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	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.	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.
Overall Study Failed Pharmacokinetics	1	0
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Sodium Nitrite n=7 Participants 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.	Placebo n=8 Participants 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.	Total n=15 Participants Total of all reporting groups
Age, Continuous	77.1 years STANDARD_DEVIATION 6.2 • n=7 Participants	74.6 years STANDARD_DEVIATION 3.5 • n=8 Participants	75.7 years STANDARD_DEVIATION 4.9 • n=15 Participants
Sex: Female, Male Female	1 Participants n=7 Participants	4 Participants n=8 Participants	5 Participants n=15 Participants
Sex: Female, Male Male	6 Participants n=7 Participants	4 Participants n=8 Participants	10 Participants n=15 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	7 participants n=7 Participants	8 participants n=8 Participants	15 participants n=15 Participants
Ejection Fraction	50.9 Percentage of blood STANDARD_DEVIATION 10.1 • n=7 Participants	54.8 Percentage of blood STANDARD_DEVIATION 9.7 • n=8 Participants	51.4 Percentage of blood STANDARD_DEVIATION 9.7 • n=15 Participants

PRIMARY outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Population: 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.

Assessment of peak Oxygen uptake (VO2) maximum via symptom limited exercise testing

Outcome measures

Measure	Sodium Nitrite n=7 Participants 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.	Placebo n=7 Participants 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.
Cardiorespiratory Fitness VO2 at Rest, last 30 sec, Pre-treatment	4.1 ml/kg/min Standard Deviation 1.5	4.0 ml/kg/min Standard Deviation 0.5
Cardiorespiratory Fitness VO2 at Rest, last 30 sec, Post-treatment	5.1 ml/kg/min Standard Deviation 1.0	4.5 ml/kg/min Standard Deviation 0.8
Cardiorespiratory Fitness VO2 at Peak Exercise, last 30 sec, Pre-treatment	18.6 ml/kg/min Standard Deviation 4.3	19.0 ml/kg/min Standard Deviation 3.9
Cardiorespiratory Fitness VO2 at Peak Exercise, last 30 sec, Post-treatment	19.6 ml/kg/min Standard Deviation 7.9	15.9 ml/kg/min Standard Deviation 7.7
Cardiorespiratory Fitness VO2 at Peak Exercise, last 30 sec, change	1.4 ml/kg/min Standard Deviation 5.2	-3.4 ml/kg/min Standard Deviation 5.2

SECONDARY outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Population: 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.

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.

Outcome measures

Measure	Sodium Nitrite n=7 Participants 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.	Placebo n=7 Participants 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.
Perceived Fatigability RPE during last minute of the test, Pre-treatment	9.1 Units on a scale Standard Deviation 2.6	10.8 Units on a scale Standard Deviation 4.0
Perceived Fatigability RPE during last minute of the test, Change	-1.2 Units on a scale Standard Deviation 2.0	-0.2 Units on a scale Standard Deviation 1.6
Perceived Fatigability RPE during last minute of the test, Post-treatment	8.3 Units on a scale Standard Deviation 1.5	10.3 Units on a scale Standard Deviation 3.3

SECONDARY outcome

Timeframe: Week 3 (pre drug) to week 10(post drug); approx. 8 weeks

Population: Magnetic resonance spectroscopy equipment had unexpected limited availability, which is why so few participants were analyzed.

Phosphocreatine reuptake after exercise during the kicking exercise in the 31P MRS (magnetic resonance spectroscopy)

Outcome measures

Measure	Sodium Nitrite n=2 Participants 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.	Placebo n=1 Participants 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.
Bioenergetics: In-Vivo 31P MRS Respirations K PCr, Pre-treatment	.028 1/s Standard Deviation .003	.019 1/s Standard Deviation 0
Bioenergetics: In-Vivo 31P MRS Respirations K PCr, Post-treatment	.028 1/s Standard Deviation .011	.022 1/s Standard Deviation 0

SECONDARY outcome

Timeframe: Week 5 (pre-drug) to week 16 (post-drug); approx. 8 weeks

Population: Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability.

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.

Outcome measures

Measure	Sodium Nitrite n=4 Participants 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.	Placebo n=5 Participants 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.
Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis O2 Consumption, Pre-treatment	34.6 pmol/(s*mg) Standard Deviation 16.5	57.7 pmol/(s*mg) Standard Deviation 14.8
Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis O2 Consumption, Post-treatment	61.6 pmol/(s*mg) Standard Deviation 36.2	46.0 pmol/(s*mg) Standard Deviation 20.0
Bioenergetics: Ex-Vivo Mitochondrial Respiration Analysis O2 Consumption, Overall change	27.1 pmol/(s*mg) Standard Deviation 27.4	-11.7 pmol/(s*mg) Standard Deviation 11.3

SECONDARY outcome

Timeframe: Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks

Population: Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability.

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.

Outcome measures

Measure	Sodium Nitrite n=2 Participants 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.	Placebo n=3 Participants 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.
Exercise-induced Changes in Pulmonary Arterial Pressure mPAP at Rest, Pre-treatment	11.0 mmHg Standard Deviation 4.2	16.0 mmHg Standard Deviation 2.0
Exercise-induced Changes in Pulmonary Arterial Pressure mPAP at Rest, Post-treatment	17.5 mmHg Standard Deviation 7.8	15.3 mmHg Standard Deviation 1.5
Exercise-induced Changes in Pulmonary Arterial Pressure mPAP at Peak Exercise, Pre-treatment	28.5 mmHg Standard Deviation 5.0	41.7 mmHg Standard Deviation 15.1
Exercise-induced Changes in Pulmonary Arterial Pressure mPAP at Peak Exercise, Post-treatment	29.0 mmHg Standard Deviation 1.4	34.7 mmHg Standard Deviation 13.7

SECONDARY outcome

Timeframe: Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks

Population: Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability.

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.

Outcome measures

Measure	Sodium Nitrite n=2 Participants 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.	Placebo n=3 Participants 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.
Exercise-induced Changes in Pulmonary Capillary Wedge Pressure PCWP at Rest, Pre-treatment	5.5 mmHg Standard Deviation 0.7	8.3 mmHg Standard Deviation 2.1
Exercise-induced Changes in Pulmonary Capillary Wedge Pressure PCWP at Rest, Post-treatment	8.5 mmHg Standard Deviation 12.0	5.7 mmHg Standard Deviation 5.0
Exercise-induced Changes in Pulmonary Capillary Wedge Pressure PCWP at Peak Exercise, Pre-treatment	11.0 mmHg Standard Deviation 0	22.7 mmHg Standard Deviation 5.5
Exercise-induced Changes in Pulmonary Capillary Wedge Pressure PCWP at Peak Exercise, Post-treatment	11.5 mmHg Standard Deviation 7.8	20.3 mmHg Standard Deviation 10.6

SECONDARY outcome

Timeframe: Week 3 (pre-drug) to week 10 (post drug); approx 8 weeks

Population: Smaller amount of subjects were analyzed due to unexpected problems with specialized testing equipment availability.

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.

Outcome measures

Measure	Sodium Nitrite n=2 Participants 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.	Placebo n=3 Participants 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.
Patients With Pulmonary Hypertension	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

Actigraph device-specific activity steps on daily-wear wrist device based on movement.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Steps From Accelerometry Assessment of Daily Activity Steps, Change	-9657 Counts/day Standard Deviation 30110	-366 Counts/day Standard Deviation 18251
Steps From Accelerometry Assessment of Daily Activity Actigraph Steps, Pre-treatment	58399 Counts/day Standard Deviation 22586	54122 Counts/day Standard Deviation 14213
Steps From Accelerometry Assessment of Daily Activity Steps, Post-treatment	48741 Counts/day Standard Deviation 25534	53757 Counts/day Standard Deviation 18107

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Sedentary Events From Accelerometry Assessment of Daily Activity # of sedentary bouts/day, Pre-treatment	29.7 bouts/day Standard Deviation 28.5	24.0 bouts/day Standard Deviation 17.2
Sedentary Events From Accelerometry Assessment of Daily Activity # of sedentary bouts/day, Post-treatment	23.7 bouts/day Standard Deviation 27.6	24.7 bouts/day Standard Deviation 24.3
Sedentary Events From Accelerometry Assessment of Daily Activity # of sedentary bouts/day, Change	-6.0 bouts/day Standard Deviation 31.3	0.7 bouts/day Standard Deviation 17.4

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Light Activity Duration From Accelerometry Assessment of Daily Activity Light activity (sec/day), Pre-treatment	3288 seconds/day Standard Deviation 715	3317 seconds/day Standard Deviation 340
Light Activity Duration From Accelerometry Assessment of Daily Activity Light activity (sec/day), Change	-422 seconds/day Standard Deviation 903	-94 seconds/day Standard Deviation 814
Light Activity Duration From Accelerometry Assessment of Daily Activity Light activity (sec/day), Post-treatment	2866 seconds/day Standard Deviation 501	3224 seconds/day Standard Deviation 793

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Moderate to Vigorous Physical Activity From Accelerometry Assessment of Daily Activity MVPA, Change	-211.5 minutes/day Standard Deviation 589.9	2.333 minutes/day Standard Deviation 254.4
Moderate to Vigorous Physical Activity From Accelerometry Assessment of Daily Activity MVPA, Pre-treatment	719.3 minutes/day Standard Deviation 597.1	545.8 minutes/day Standard Deviation 237.3
Moderate to Vigorous Physical Activity From Accelerometry Assessment of Daily Activity MVPA, Post-treatment	507.8 minutes/day Standard Deviation 456.3	548.2 minutes/day Standard Deviation 255.3

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Vector Magnitude Counts From Accelerometry Assessment of Daily Activity Vector Magnitude, Pre-treatment	1192.5 Counts/day Standard Deviation 379.5	1205 Counts/day Standard Deviation 205
Vector Magnitude Counts From Accelerometry Assessment of Daily Activity Vector Magnitude, Post-treatment	1043 Counts/day Standard Deviation 357	1122.7 Counts/day Standard Deviation 318.5
Vector Magnitude Counts From Accelerometry Assessment of Daily Activity Vector Magnitude, Change	-149.4 Counts/day Standard Deviation 329	-82.3 Counts/day Standard Deviation 337.3

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Sedentary Event Duration From Accelerometry Assessment of Daily Activity Average Sedentary Bout Duration, Pre	14.8 minutes/bout Standard Deviation 3	13.6 minutes/bout Standard Deviation 2.3
Sedentary Event Duration From Accelerometry Assessment of Daily Activity Average Sedentary Bout Duration, Post	14.4 minutes/bout Standard Deviation 2.2	12.0 minutes/bout Standard Deviation 6.0
Sedentary Event Duration From Accelerometry Assessment of Daily Activity Average Sedentary Bout Duration, Chg	-0.4 minutes/bout Standard Deviation 2.4	-1.6 minutes/bout Standard Deviation 4.9

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Light Activity Events Percentage of Day From Accelerometry Assessment of Daily Activity % in Light Activity, Pre-Treatment	.320 % of day Standard Deviation .041	.359 % of day Standard Deviation .026
Light Activity Events Percentage of Day From Accelerometry Assessment of Daily Activity % in Light Activity, Post-Treatment	.306 % of day Standard Deviation .033	.359 % of day Standard Deviation .327
Light Activity Events Percentage of Day From Accelerometry Assessment of Daily Activity % in Light Activity,Change	-0.014 % of day Standard Deviation 0.046	-0.033 % of day Standard Deviation 0.078

SECONDARY outcome

Timeframe: Week 1(pre-drug) to week 16(post-drug); approx. 16 weeks

Population: Only 6 subjects in either arm had functioning accelerometers with data that could be extracted and analyzed.

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.

Outcome measures

Measure	Sodium Nitrite n=6 Participants 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.	Placebo n=6 Participants 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.
Moderate to Vigorous Physical Activity Percentage From Accelerometry Assessment of Daily Activity % in MVPA, Pre-treatment	0.066 Percentage of day Standard Deviation 0.041	0.059 Percentage of day Standard Deviation 0.023
Moderate to Vigorous Physical Activity Percentage From Accelerometry Assessment of Daily Activity % in MVPA, Post-treatment	0.054 Percentage of day Standard Deviation 0.045	0.055 Percentage of day Standard Deviation 0.025
Moderate to Vigorous Physical Activity Percentage From Accelerometry Assessment of Daily Activity % in MVPA, Change	-0.012 Percentage of day Standard Deviation 0.032	-0.004 Percentage of day Standard Deviation 0.023

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks

Change in adiponectin

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 week

Change in blood levels to assess efficacy of study drug

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks

Change in brain natriuretic protein (BNP)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 3 (pre-drug) to week 10 (post drug); approx. 8 weeks

Invasive cardiopulmonary exercise testing

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Non-invasive cardiopulmonary exercise testing

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the Montreal Cognitive Assessment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the Charlson Comorbidity Index

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre drug to week 16 post drug

Medications for comorbidity managment

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre-drug to week 16 post drug

Change in cardiac strain

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the Pittsburgh Fatigability Index

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 screening pre-drug to week 16 post drug

Physician assessment of frailty using the Canadian Clinical Frailty Scale

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 week

Change in DNA from Polymerase Chain Reaction analysis

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 week

Change in glomerular filtration rate (GFR)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 week

Change in glycosylated hemoglobin (HgbA1c)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre drug to week 16 post drug

Change in hematocrit

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre drug to week 16 post drug

Change in hemoglobin

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre drug to week 16 post drug

Change in Blood pressure

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 1 pre drug to week 16 post drug

Change in heart rate

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 week

Change in protein content of muscle fiber

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Assessment of blood flow during exercise

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the McGill Pain Questionnaire

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in score on Standard Physical Performance Battery at visit 2 pre drug and visit 5

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the CHAMPS (Community Healthy Activities Program for Seniors) Activities Questionnaire for Older Adults-physical activity

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the Kansas City Cardiomyopathy Questionnaire subject self reported responses

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in distance on six minute walk test

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 2(pre drug) to Week 10( post drug); approx. 8 weeks

Change in pre and post scores on the Sullivan Cardiac Self Efficacy questionnaire

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 5 (pre drug) to week 16 (post drug); approx. 8 weeks

Change in thyroid stimulating hormone (TSH)

Outcome measures

Outcome data not reported

Adverse Events

Treatment Arm

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Control Arm

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment Arm n=7 participants at risk 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.	Control Arm n=8 participants at risk 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.
Cardiac disorders Low diastolic blood pressure	14.3% 1/7 • Number of events 1 • 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.	0.00% 0/8 • 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.
Gastrointestinal disorders Constipation	14.3% 1/7 • Number of events 2 • 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.	12.5% 1/8 • Number of events 1 • 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.
Cardiac disorders Palpitations	14.3% 1/7 • Number of events 1 • 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.	25.0% 2/8 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Blood and lymphatic system disorders Hematoma	50.0% 1/2 • Number of events 1 • 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.	0.00% 0/3 • 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.
Eye disorders Subconjunctival Hemorrhage	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Cardiac disorders Bradycardia	0.00% 0/7 • 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.	0.00% 0/8 • 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.
Gastrointestinal disorders Chest pain	0.00% 0/7 • 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.	0.00% 0/8 • 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.
Injury, poisoning and procedural complications Pain at Biopsy site	0.00% 0/7 • 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.	0.00% 0/8 • 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.
Skin and subcutaneous tissue disorders Swelling of cheeks	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
General disorders Fatigue	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 2 • 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.
Musculoskeletal and connective tissue disorders Leg Cramping	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 3 • 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.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 3 • 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.
Gastrointestinal disorders Vomiting	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
General disorders Dry Mouth	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Backache	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection-like symptoms	14.3% 1/7 • Number of events 3 • 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.	12.5% 1/8 • Number of events 2 • 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.
Renal and urinary disorders Difficulty Urinating	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 2 • 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.
Psychiatric disorders Depression	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Social circumstances Unable to afford daily medications	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.
Investigations Took investigational drug/placebo early	0.00% 0/7 • 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.	12.5% 1/8 • Number of events 1 • 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.

Additional Information

Tara Sheila Stakich

University of Pittsburgh

Phone: 412-864-2082

Email: tss54@pitt.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place