Trial Outcomes & Findings for Oral Nitrite for Older Heart Failure Patients (NCT NCT02457260)
NCT ID: NCT02457260
Last Updated: 2018-09-18
Results Overview
Obtained via analysis of skeletal muscle biopsy of the vastus lateralis, Polymerase chain reaction (PCR) to assess pertinent gene expression within the pathways of ubiquitin \[muscle ring finger protein 1 (MuRF), Atrogin1, Forkhead Box 03 (FoxO)\], additionally Fibronectin type III domain-containing protein 5, the precursor of irisin (FNDC5), Peroxisome proliferator-activated receptor gamma co activator 1-alpha (PGC1α), and Sirtuin 3 were assessed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Baseline; PRE and 4 weeks; POST
Results posted on
2018-09-18
Participant Flow
Participant milestones
| Measure |
Healthy Control
12 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
7 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
2 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
12
|
7
|
2
|
|
Overall Study
COMPLETED
|
10
|
4
|
1
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Oral Nitrite for Older Heart Failure Patients
Baseline characteristics by cohort
| Measure |
Healthy Control
n=12 Participants
12 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
Heart Failure With Preserved Ejection Fraction (HFpEF)
n=7 Participants
7 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
Heart Failure With Reduced Ejection Fraction(HFrEF)
n=2 Participants
2 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: Health Control- 2 and 1 HFrEF participants have missing data for the gene analysis due to muscle samples not providing a clean reference value for inclusion of data analysis.. 6 subjects withdrawn from the study.
Obtained via analysis of skeletal muscle biopsy of the vastus lateralis, Polymerase chain reaction (PCR) to assess pertinent gene expression within the pathways of ubiquitin \[muscle ring finger protein 1 (MuRF), Atrogin1, Forkhead Box 03 (FoxO)\], additionally Fibronectin type III domain-containing protein 5, the precursor of irisin (FNDC5), Peroxisome proliferator-activated receptor gamma co activator 1-alpha (PGC1α), and Sirtuin 3 were assessed.
Outcome measures
| Measure |
Healthy Control
n=8 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- FoX O-POST
|
10.74 Relative Expression
Standard Deviation 0.30
|
10.81 Relative Expression
Standard Deviation 0.61
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- PGC1α-PRE
|
10.03 Relative Expression
Standard Deviation 0.14
|
10.06 Relative Expression
Standard Deviation 0.27
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR -FNDC5 -PRE
|
12.04 Relative Expression
Standard Deviation 0.45
|
11.91 Relative Expression
Standard Deviation 0.53
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- FNDC5-POST
|
11.79 Relative Expression
Standard Deviation 0.48
|
11.76 Relative Expression
Standard Deviation 0.34
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- Sirtuin 3-PRE
|
9.25 Relative Expression
Standard Deviation 0.23
|
9.12 Relative Expression
Standard Deviation 0.10
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR-Sirtuin 3-POST
|
9.10 Relative Expression
Standard Deviation 0.18
|
9.07 Relative Expression
Standard Deviation 0.14
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR-MuRF-PRE
|
11.64 Relative Expression
Standard Deviation 0.25
|
11.90 Relative Expression
Standard Deviation 0.22
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR-MuRF-POST
|
11.46 Relative Expression
Standard Deviation 0.21
|
11.57 Relative Expression
Standard Deviation 0.46
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR-Atrogin1-PRE
|
13.41 Relative Expression
Standard Deviation 0.13
|
13.55 Relative Expression
Standard Deviation 0.38
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR-Atrogin1-POST
|
13.30 Relative Expression
Standard Deviation 0.25
|
13.12 Relative Expression
Standard Deviation 0.48
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- FoX O-PRE
|
10.93 Relative Expression
Standard Deviation 0.27
|
10.95 Relative Expression
Standard Deviation 0.44
|
—
|
|
Skeletal Muscle Bioenergetics- Polymerase Chain Reaction (PCR)
PCR- PGC1α-POST
|
9.96 Relative Expression
Standard Deviation 0.22
|
9.70 Relative Expression
Standard Deviation 0.48
|
—
|
PRIMARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: 2 Controls, 1 HFpEF and 1 HFrEF have no data for mitochondrial function due to no FCCP response or potential cytochrome c response. 6 subjects withdrawn from the study.
Obtained via analysis of skeletal muscle biopsy of the vastus lateralis, Mitochondrial function was assessed using respirometry (State 3.12).
Outcome measures
| Measure |
Healthy Control
n=8 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=3 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Skeletal Muscle Bioenergetics - Mitochondrial Function
Mitochondrial function- Fiber 1 State 3.12 PRE
|
108.88 nmol O / sec/ mg
Standard Deviation 51.69
|
122.99 nmol O / sec/ mg
Standard Deviation 46.75
|
—
|
|
Skeletal Muscle Bioenergetics - Mitochondrial Function
Mitochondrial function- Fiber 1 State 3.12 POST
|
123.59 nmol O / sec/ mg
Standard Deviation 35.82
|
169.77 nmol O / sec/ mg
Standard Deviation 69.33
|
—
|
|
Skeletal Muscle Bioenergetics - Mitochondrial Function
Mitochondrial function- Fiber 2 State 3.12 PRE
|
122.84 nmol O / sec/ mg
Standard Deviation 29.92
|
229.03 nmol O / sec/ mg
Standard Deviation 82.63
|
—
|
|
Skeletal Muscle Bioenergetics - Mitochondrial Function
Mitochondrial function- Fiber 2 State 3.12 POST
|
124.68 nmol O / sec/ mg
Standard Deviation 70.04
|
120.44 nmol O / sec/ mg
Standard Deviation 26.74
|
—
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: Patients that completed pre post testing in each of the three arms were include in analysis. 6 subjects withdrawn from the study.
Platelet bioenergetics (using Seahorse XF analysis), i.e., including glycolytic(OLIGO) as well as basal and maximal respiratory rates and extracellular acidification rate.
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Serology-platelet Bioenergetics
Basal respiratory rates-PRE
|
122.77 pmol/minute
Standard Deviation 35.21
|
110.17 pmol/minute
Standard Deviation 22.89
|
148.71 pmol/minute
Standard Deviation 0
|
|
Serology-platelet Bioenergetics
Basal respiratory rates-POST
|
120.44 pmol/minute
Standard Deviation 31.05
|
120.90 pmol/minute
Standard Deviation 29.67
|
119.78 pmol/minute
Standard Deviation 0
|
|
Serology-platelet Bioenergetics
OLIGO OCR- PRE
|
29.38 pmol/minute
Standard Deviation 14.05
|
34.59 pmol/minute
Standard Deviation 22.80
|
29.49 pmol/minute
Standard Deviation 0
|
|
Serology-platelet Bioenergetics
OLIGO OCR- POST
|
27.28 pmol/minute
Standard Deviation 8.15
|
29.81 pmol/minute
Standard Deviation 11.30
|
11.25 pmol/minute
Standard Deviation 0
|
|
Serology-platelet Bioenergetics
maximal respiratory rates- PRE
|
181.08 pmol/minute
Standard Deviation 56.28
|
157.00 pmol/minute
Standard Deviation 46.64
|
188.09 pmol/minute
Standard Deviation 0
|
|
Serology-platelet Bioenergetics
maximal respiratory rates- POST
|
185.52 pmol/minute
Standard Deviation 52.83
|
144.99 pmol/minute
Standard Deviation 50.01
|
89.31 pmol/minute
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: All patients that have both pre and post data were assessed for all three groups. 6 subjects withdrawn from the study.
Continuous metabolic gas collection or a cardiopulmonary exercise test occurred during a constant speed-steady state treadmill walking protocol (1.5mph at a 0% grade) for 5 minutes. During the final minute of the walking protocol oxygen consumption (VO2) was assessed to determined if the patient reached steady state VO2. Steady state VO2 was assessed by a less than 5% change in VO2 for a 30 second period of time. The 30 second average time is represented below in units of measure ml/kg/min. This is to show change in efficiency of performance of the constant speed test a decrease in VO2 from pre to post indicates greater efficiency.
Outcome measures
| Measure |
Healthy Control
n=9 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Measures of Physical Function- Cardiopulmonary Exercise Test (CPX)
Pre
|
13.29 ml/kg/min
Standard Deviation 4.14
|
11.55 ml/kg/min
Standard Deviation 0.66
|
10.05 ml/kg/min
Standard Deviation 0
|
|
Measures of Physical Function- Cardiopulmonary Exercise Test (CPX)
Post
|
11.27 ml/kg/min
Standard Deviation 2.76
|
11.79 ml/kg/min
Standard Deviation 2.75
|
10.50 ml/kg/min
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: All patients that have both pre and post data were assessed for all three groups. 6 subjects withdrawn from the study.
4 meter gait speed assessed as part of the short performance physical battery (SPPB). This assessment evaluates how long it take a person can cover four meters at their usual walking speed from a stop when a person says go. This was completed twice to find the fastest speed was used as the variable.
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Measures of Physical Function- Gait Speed
Gait Speed- Pre
|
4.32 seconds
Standard Deviation 0.78
|
5.6 seconds
Standard Deviation 2.24
|
4.22 seconds
Standard Deviation 0
|
|
Measures of Physical Function- Gait Speed
Gait Speed- Post
|
4.36 seconds
Standard Deviation 0.74
|
5.36 seconds
Standard Deviation 1.81
|
4.06 seconds
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: All patients that have both pre and post data were assessed for all three groups. 6 subjects withdrawn from the study.
Handgrip is used as a measure of upper body strength. three trials on each hand were completed with the patient seated and the arm at a right angle. For the purposes of this analysis all trials were averaged together.
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Measures of Physical Function- Handgrip
Handgrip- PRE
|
26.53 kg
Standard Deviation 7.69
|
27.02 kg
Standard Deviation 5.15
|
25.25 kg
Standard Deviation 0
|
|
Measures of Physical Function- Handgrip
Handgrip-POST
|
26.5 kg
Standard Deviation 8.61
|
26.02 kg
Standard Deviation 4.23
|
25.41 kg
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: All patients that have both pre and post data were assessed for all three groups. 6 subjects withdrawn from the study.
Balance was assessed as part of the short performance physical battery (SPPB). This assessment evaluates three components of static stand (stands with their feet together), semi tandem (stand with the heal of one foot beside the toe of the other foot), Tandem (stands with one foot directly in front of the other). Each test is held for as many seconds as they can up to ten seconds. Static and semi tandem if held for 10 second counts as 1 point if not held it is 0 points, tandem stand if held for 10 second is 2 points, if held for 3 to9.99 it is 1 point, otherwise 0 points. Total points are added up for all balance tests for a composite score with the higher the score the better and maximum being 4, minimum 0.
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Measures of Physical Function- Balance
SPPB (Balance) - PRE
|
3.5 score on a scale
Standard Deviation 0.71
|
3.25 score on a scale
Standard Deviation 1.5
|
1 score on a scale
Standard Deviation 0
|
|
Measures of Physical Function- Balance
SPPB (Balance)-POST
|
3.4 score on a scale
Standard Deviation 0.52
|
3.75 score on a scale
Standard Deviation 0.5
|
3 score on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: Kansas City Cardiomyopathy Questionnaire (KCCQ)- is a standard tool to assess the quality of life of the heart failure patients. Control patients were not assessed via KCCQ given it is not a valid tool for healthy. All HF patients that completed pre and post assessment were analyzed. 6 subjects withdrawn from the study.
Kansas City Cardiomyopathy Questionnaire (KCCQ)- is a standard tool to assess the quality of life of the heart failure patients. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains with the higher the score (0-100) the better the health status.
Outcome measures
| Measure |
Healthy Control
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Quality of Life Assessment- In Heart Failure
KCCQ- PRE
|
—
|
83.40 scores on a scale
Standard Deviation 13.54
|
94.79 scores on a scale
Standard Deviation 0
|
|
Quality of Life Assessment- In Heart Failure
KCCQ-POST
|
—
|
86.13 scores on a scale
Standard Deviation 18.04
|
84.90 scores on a scale
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: Patients that completed pre post testing in each of the three arms were include in analysis. 6 subjects withdrawn from the study.
Inflammatory marker (C-reactive protein \[CRP\])
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Serology-Inflammatory Marker
CRP-PRE
|
1.37 mg/L
Standard Deviation 1.4
|
0.58 mg/L
Standard Deviation 0.52
|
27.57 mg/L
Standard Deviation 0
|
|
Serology-Inflammatory Marker
CRP-POST
|
0.97 mg/L
Standard Deviation 0.91
|
1.26 mg/L
Standard Deviation 1.14
|
5.43 mg/L
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: On analysis of data for this report it was found that three control samples had been missed on initial running of nitrate/nitrite bring the N=7 for that assessment. 6 subjects withdrawn from the study.
plasma nitrite and plasma nitrate levels pre and post 4 week intervention
Outcome measures
| Measure |
Healthy Control
n=7 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Serology-plasma Nitrite and Nitrate
Plasma Nitrite- PRE
|
2.43 µm
Standard Deviation 2.96
|
0.11 µm
Standard Deviation 0.04
|
0.04 µm
Standard Deviation 0
|
|
Serology-plasma Nitrite and Nitrate
Plasma Nitrite- POST
|
0.50 µm
Standard Deviation 0.33
|
0.35 µm
Standard Deviation 0.15
|
0.11 µm
Standard Deviation 0
|
|
Serology-plasma Nitrite and Nitrate
Plasma Nitrate- PRE
|
61.01 µm
Standard Deviation 15.64
|
34.91 µm
Standard Deviation 10.44
|
39.81 µm
Standard Deviation 0
|
|
Serology-plasma Nitrite and Nitrate
Plasma Nitrate- POST
|
75.30 µm
Standard Deviation 15.64
|
44.2 µm
Standard Deviation 5.97
|
67.68 µm
Standard Deviation 0
|
SECONDARY outcome
Timeframe: Baseline; PRE and 4 weeks; POSTPopulation: Patients that completed pre post testing in each of the three arms were include in analysis. 6 subjects withdrawn from the study.
Platelet bioenergetics (using Seahorse XF analysis), i.e., extracellular acidification rate.
Outcome measures
| Measure |
Healthy Control
n=10 Participants
10 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=4 Participants
4 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=1 Participants
1 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Serology-platelet Bioenergetics-1
extracellular acidification rate -PRE
|
3.78 mpH/min
Standard Deviation 3.06
|
3.22 mpH/min
Standard Deviation 3.02
|
7.34 mpH/min
Standard Deviation 0
|
|
Serology-platelet Bioenergetics-1
extracellular acidification rate -POST
|
3.67 mpH/min
Standard Deviation 2.61
|
3.96 mpH/min
Standard Deviation 3.68
|
0.66 mpH/min
Standard Deviation 0
|
Adverse Events
Healthy Control
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
HFpEF
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
HFrEF
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Healthy Control
n=12 participants at risk
12 healthy adults, age 70 or older to receive 14 Nitrogen (14N) sodium nitrite, 40 mg tid
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFpEF
n=7 participants at risk
7 adults with heart failure and preserved ejection fraction age 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
HFrEF
n=2 participants at risk
2 adults with heart failure and reduced ejection fraction aged 70 or older to receive 14N sodium nitrite, 20 or 40 mg tid depending on dose stratification for safety
14 N Sodium Nitrite: oral formulation of sodium nitrite 40 mg three times daily for 4 weeks
|
|---|---|---|---|
|
Gastrointestinal disorders
Belly Pain
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
3/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Gastrointestinal disorders
Dry Mouth
|
41.7%
5/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Fatigue
|
16.7%
2/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Vascular disorders
Flushing
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Nervous system disorders
Headache
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Vascular disorders
Hypotension
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
71.4%
5/7 • patients were assessed over 4 weeks of the nitrite intervention
|
50.0%
1/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Nervous system disorders
Impaired Depth Perception
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
Knee Strain
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
leg cramps
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
leg twinge
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Lightheadedness
|
25.0%
3/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
50.0%
1/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
Lumbrosacral strain
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Infections and infestations
Malaise With Flu
|
16.7%
2/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness- upper leg
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Infections and infestations
nausea
|
16.7%
2/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Renal and urinary disorders
Nocturia
|
25.0%
3/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Tension in Head
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Renal and urinary disorders
URI
|
16.7%
2/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Vomiting
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Psychiatric disorders
Depression
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Cramp
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Twinge
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
dizzy
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Itchy Eyes
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Blood Blister
|
8.3%
1/12 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Insomnia
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
General disorders
Increase in poor coordination
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Skin and subcutaneous tissue disorders
Scaly itchy patch on thigh
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Cardiac disorders
increased heart rate
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Nervous system disorders
syncopal episode
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Cardiac disorders
Chest tightness
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Cardiac disorders
Change in blood pressure
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
back pain resolved
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
leg cramps resolved
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Cardiac disorders
Diastolic
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
|
Musculoskeletal and connective tissue disorders
Shin spasm pain recurring
|
0.00%
0/12 • patients were assessed over 4 weeks of the nitrite intervention
|
14.3%
1/7 • patients were assessed over 4 weeks of the nitrite intervention
|
0.00%
0/2 • patients were assessed over 4 weeks of the nitrite intervention
|
Additional Information
Daniel E. Forman - Chief of a section of Geriatrics Cardiology
University of Pittsburgh
Phone: 412-864-2507
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place