An Early Phase 1 interventional study of Active lozenge and Placebo in Heart Failure With Normal Ejection Fraction, sponsored by MaineHealth. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-06.
Sponsored by MaineHealth · Early Phase 1, Interventional, and Treatment
The objective of this project is to determine if Neo40, a nitric oxide generating lozenge, when consumed twice daily by subjects with HFpEF, will increase exercise tolerance, decrease symptoms and improve quality of life for patients.
Heart failure (HF) is the most common principal diagnosis for hospital admission in patients over 65 years old. There are two types of HF, those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF). Approximately half of patients with the clinical syndrome of HF have preserved systolic function. HEpEF is becoming more prevalent with aging of the population and obesity. There are only two class I recommendations for the treatment of HFpEF, which are controlling blood pressure and the use of diuretics to relieve symptoms. Exercise training is another approach to improving symptoms, however it may be poorly tolerated.
Nitrate supplement in the form of concentrated beetroot juice was recently shown to improve exercise tolerance in patients with HFpEF. (1) Beetroot juice contains high concentration of nitrate (NO3). This is metabolized to nitrite (NO2). It enters the blood stream, where it is further reduced to nitric oxide (NO) resulting in intense vasodilation.
Patients with diastolic dysfunction are often asymptomatic at rest but complain of dyspnea with exertion. Increase in heart rate with exercise causes reduced diastolic filling time and increases left sided filling pressure. Borloug, et al demonstrated this with right heart catheterization and supine exercise in patients with diastolic dysfunction. Infusion of NO2 resulted in decreased filling pressures and increased cardiac output. (2)
Neo40 is a new product made from concentrated beetroot juice in the form of a lozenge designed to dissolve on the tongue. NO3 supplement causes vasodilatation only in the setting of hypoxia and acidosis resulting in targeted vasodilatation.
Diagnosis of HFpEF, defined as:
Exclusion Criteria:
Subject will take active lozenge (Vitamin C, Vitamin B12, Nitric Oxide Blend, L-citrulline, Sodium Nitrite) for one week, perform cardiac testing then take placebo lozenge for one week and perform cardiac testing.
Dietary Supplement: Active lozenge · Drug: Placebo
Subject will take placebo lozenge for one week, perform cardiac testing then take active lozenge (Vitamin C, Vitamin B12, Nitric Oxide Blend, L-citrulline, Sodium Nitrite) for one week and perform cardiac testing.
Dietary Supplement: Active lozenge · Drug: Placebo
nitric oxide generating lozenge
placebo tablet
Time on Treadmill
change in total time traveled on treadmill
Time frame: after one week of active lozenges compared to one week of placebo lozenges
Metabolic Equivalents
change in metabolic equivalents on treadmill
Time frame: after one week of active lozenges compared to one week of placebo lozenges
E/E Prime
change in E/E prime on exercise echo (E/E prime is a ratio between early mitral inflow velocity and mitral annular early diastolic velocity in order to measure diastolic dysfunction)
Time frame: after one week of active lozenges compared to one week of placebo lozenges
Estimated Right Ventricular Systolic Pressure
change in estimated right ventricular systolic pressure on echo
Time frame: after one week of active lozenges compared to one week of placebo lozenges
This study was a cross over case-control study (each subject was a control for themselves).
| Milestone | Active Lozenge First | Placebo Lozenge First |
|---|---|---|
| Started | 6 | 7 |
| Completed | 4 | 5 |
| Not completed | 2 | 2 |
change in total time traveled on treadmill
| seconds | Active Lozenge | Placebo |
|---|---|---|
| Time on Treadmill | 402.8 (156 to 729) | 181.2 (180 to 660) |
change in metabolic equivalents on treadmill
| cal/min | Active Lozenge | Placebo |
|---|---|---|
| Metabolic Equivalents | 7.99 (4.2 to 12.8) | 8.46 (4.2 to 12.8) |
change in E/E prime on exercise echo (E/E prime is a ratio between early mitral inflow velocity and mitral annular early diastolic velocity in order to measure diastolic dysfunction)
| ratio | Active Lozenge | Placebo Lozenge |
|---|---|---|
| E/E Prime | 1.93 (-6.2 to 8) | -.05 (-6.8 to 2.4) |
change in estimated right ventricular systolic pressure on echo
| mmHg | Active Lozenge | Placebo |
|---|---|---|
| Estimated Right Ventricular Systolic Pressure | 11.79 (5 to 27) | 8.6 (-1.2 to 28) |
Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active Lozenge | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) |
| Placebo Lozenge | 0/9 (0%) | 0/9 (0%) | 0/9 (0%) |
| Age, Categorical(Participants) | Active Lozenge First | Placebo Lozenge First | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 0 | 2 | 2 |
| >=65 years | 4 | 3 | 7 |
| Sex: Female, Male(Participants) | Active Lozenge First | Placebo Lozenge First | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 2 | 4 | 6 |
| Race (NIH/OMB)(Participants) | Active Lozenge First | Placebo Lozenge First | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 5 | 9 |
| Region of Enrollment(participants) | Active Lozenge First | Placebo Lozenge First | Total |
|---|---|---|---|
| United States | 4 | 5 | 9 |
| Diagnosis of HFpEF(Participants) | Active Lozenge First | Placebo Lozenge First | Total |
|---|---|---|---|
| Count of participants | 4 | 5 | 9 |
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