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The purpose of this study is to do the work that is necessary and sufficient for setting up an appropriate multi-center, randomized clinical trial (RCT) of a new therapy for heart failure: inorganic nitrate. The investigators will first determine the effects and palatability of ~12.8mmol KNO3 (an oral pill) as compared to the roughly equivalent amount of nitrate in 2 beetroot juice (BRJ) Sports Shots (by James White Drinks). Next, the investigators will determine the effects of inorganic nitrate (KNO3 in an oral pill format) on blood pressure, blood nitrate levels, breath nitric oxide (NO) levels, and exercise performance in a dose-response study. Third, the investigators will perform a small phase II chronic treatment study that will allow them to determine the best primary endpoint and the numbers of patients the investigators will need to study in the large, multi-center RCT to follow this project. In the small study and in the RCT to follow, the investigators will determine whether inorganic nitrate can improve aerobic exercise capacity, muscle power, and speed of muscle contraction, and lessen the effort of breathing during exercise.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 10mmol KNO3 | Experimental | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. |
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| 20mmol KNO3 | Experimental | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KNO3, potassium nitrate | Drug | Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
| Measure | Description | Time Frame |
|---|---|---|
| VO2peak | peak oxygen consumption during treadmill exercise | acute - 2.5 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Peak Muscle Power | Participants completed measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement). | acute - 2 hours post dose |
| Blood Nitrite Levels |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Linda R Peterson, MD | Washington University School of Medicine | Principal Investigator |
| Andrew R Coggan, PhD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
HIPPA-related data will not be available for publishing. Study results will be published in accordance with journal, institution, and HIPPA guidelines.
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| ID | Title | Description |
|---|---|---|
| FG000 | 10mmol KNO3, Then 20mmol KNO3 | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10mmol KNO3) in 2 gelatin capsules during dose visit 1 and the otherv20 mmol KNO3 during dose visit 2. KNO3, potassium nitrate: Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
| FG001 | 20mmol KNO3, Then 10mmol KNO3 | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and 10mmol KNO3 during dose visit 2. KNO3, potassium nitrate: Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 or 20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 or 20 mmol KNO3) during dose visit 2. The dose order will be randomized. KNO3, potassium nitrate: Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | VO2peak | peak oxygen consumption during treadmill exercise | Posted | Mean | Standard Deviation | mL/kg/min | acute - 2.5 hours post dose |
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Adverse events were monitored throughout the study period (about 6 weeks)
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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 | 10mmol KNO3 | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (10 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (20 mmol KNO3) during dose visit 2. The dose order will be randomized. KNO3, potassium nitrate: Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Lauren Park | Washington University in St. Louis | 3143633915 | l.park@wustl.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 | Jan 7, 2020 | Oct 3, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 15, 2018 | Oct 3, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C023844 | potassium nitrate |
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Subjects will receive one drug dose on the first dose visit and the second drug dose on the second dose visit. The order of the two drug doses (10 and 20 mmol KNO3) will be randomized, so that some subjects will receive the lower dose first and others will receive the higher dose first
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Both the participant and the investigator will be masked to which KNO3 dose is administered at each visit. However, it is known at the outset that each patient will receive 10 mmol KNO3 during one visit and 20 mmol KNO3 at another visit, with the order randomly assigned.
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concentrations of nitrite in the blood |
| time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose) |
| Breath Nitric Oxide (NO) Level | Breath nitric oxide (NO) level will be taken via NIOX breath analyzer | time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose) |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | Peak Muscle Power | Participants completed measurements of leg muscle power by doing knee extension exercises on a dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement). | Posted | Mean | Standard Deviation | Watts/kg | acute - 2 hours post dose |
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| Secondary | Blood Nitrite Levels | concentrations of nitrite in the blood | Posted | Mean | Standard Deviation | micro M | time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose) |
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| Secondary | Breath Nitric Oxide (NO) Level | Breath nitric oxide (NO) level will be taken via NIOX breath analyzer | Posted | Mean | Standard Deviation | ppb | time 0 (before receiving the KNO3 dose) and hourly after receiving KNO3 (1, 2, and 3 hours post-dose) |
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| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | 20mmol KNO3 | Intervention: Subjects with heart failure will receive a single oral dose of potassium nitrate (20 mmol KNO3) in 2 gelatin capsules during dose visit 1 and the other dose (10 mmol KNO3) during dose visit 2. The dose order will be randomized. KNO3, potassium nitrate: Potassium nitrate (KNO3) will be given orally in 2 gelatin capsules, which will be compounded by the Barnes-Jewish Hospital Pharmacy. The doses are 10 mmol and 20 mmol KNO3. | 0 | 6 | 0 | 6 | 0 | 6 |
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| 2 hr post-ingestion KNO3 |
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| 3 hr post-ingestion KNO3 |
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| 2 hr |
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| 3 hr |
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