The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF)

Summary

The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction \<45%). The investigators hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, the investors will perform a randomized, double-blind, placebo-controlled, parallel-arm design study.

Detailed Description

Visit 1 - Screening Visit 1 will be considered the screening visit. Participants will not be required to fast for this visit. This visit will be conducted over approximately 1.5 to 2 hours. The following procedures will be completed during this visit: 1. Informed consent, if not already obtained previously. 2. Health questionnaire 3. Review of medical history and concomitant medication usage 4. Review of any patient reported eligibility criteria (e.g., agreeance to using birth control, not using phosphodiesterase, inhibitors, etc.) 5. Labs a. As this is the only blood sample collected during this visit, IV placement is not necessary at this visit. 6. Urine pregnancy test 7. Physical examination 8. NYHA classification 9. Vital signs measurements 10. Height and weight measurements 11. Resting TTE with or without contrast At the conclusion of Visit 1, eligibility criteria for each participant will be reviewed and confirmed by the PI prior to the participant completing Visit 2 procedures. Visit 2 - Baseline Visit 2 will be considered the baseline visit. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur: 1. Review of any changes to medical history and concomitant medication usage 2. Review of compliance on restrictions 3. IV placement 4. Labs 5. Vital signs measurements 6. Height, weight, hip, and waist circumference measurements 7. Low nitrate snack consumption 8. PWV and PWA After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously: 1. 0 Hour 1. Blood sampling for NO3- and NO2- and NT-proBNP 2. Breath Nitric Oxide 3. Hand grip strength assessment 4. KCCQ and MLHFQ 2. 1 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. PWV and PWA 5. DXA Scan 3. 2 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Maximal muscle power test 5. Aerobic capacity test 4. 3 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Hand grip strength assessment 5. 4 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits. After completion of the 4 hour time point, the participant will be discharged from the facility. Visit 3 - Acute Dose Administration This visit will occur within 1 month after Visit 2. Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur: 1. Review of any changes to medical history and concomitant medication usage 2. Review of compliance on restrictions 3. IV placement 4. Labs 5. Vital signs measurements 6. Height, weight, hip, and waist circumference measurements 7. Low nitrate snack consumption 8. PWV and PWA After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously: 1. 0 Hour 1. Blood sampling for NO3- and NO2- and NT-proBNP 2. Breath Nitric Oxide 3. Ingestion of investigational product 4. Hand grip strength assessment 5. KCCQ and MLHFQ 2. 1 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. PWV and PWA 3. 2 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Maximal muscle power test 5. Aerobic capacity test 4. 3 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Hand grip strength assessment 5. 4 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Review of any adverse events specifically associated with investigational medication administration 5. Dispense of 6 weeks' worth of investigational medication Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits. After completion of the 4 hour time point, the participant will be discharged from the facility. Between Visits 3 and 4 Between visits 3 and 4, participants will take the study medication provided daily. Every 2 weeks, participants will be asked to complete a Bi-weekly Adherence Survey to track compliance between Visits 3 and 4. Visit 4 - 6 Week Follow Up/End of Study Participants will be required to fast for this visit. This visit will be conducted over approximately 4 to 5 hours. Upon the participant's arrival, the following will occur: 1. Review of any changes to medical history and concomitant medication usage 2. Review of compliance on restrictions 3. Collection of any remaining investigational product 4. IV placement 5. Labs 6. Vital signs measurements 7. Height, weight, hip, and waist circumference measurements 8. Physical exam 9. Low nitrate snack consumption 10. Resting TTE with contrast 11. PWV and PWA After these procedures have been completed, the following procedures will occur each hour as follows in the order in which they are listed, if not being completed simultaneously: 1. 0 Hour a. Blood sampling for NO3- and NO2- and NT-proBNP f. Breath Nitric Oxide g. Ingestion of investigational product h. Hand grip strength assessment i. KCCQ and MLHFQ 2. 1 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. PWV and PWA 5. DXA scan 3. 2 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Maximal muscle power test 5. Aerobic capacity test 4. 3 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide 4. Hand grip strength assessment 5. 4 Hour 1. Blood sampling for NO3- and NO2- only 2. Vital signs measurements (BP and HR only) 3. Breath Nitric Oxide Note, blood sampling, vital signs, and breath nitric oxide measurements should be collected as close to the beginning of each hourly time point as possible. However, it will not be considered a protocol deviation if they are slightly delayed due to procedures such as exercise testing extending into the next hour. All other procedures can be completed within each hour as time permits. After completion of the 4 hour time point, the participant will be discharged from the facility. At this time, the participant will be considered to have completed the study.

Eligibility Criteria

Interventions