Dietary Nitrate for Heart Failure
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 17
- Locations
- 4
- Primary Endpoint
- Maximal Knee Extensor Power
Study Overview
Brief Summary
The purpose of this study is to determine if nitrates in a food, in this case - beetroot juice (BRJ) - is efficacious in improving exercise tolerance and/or peak power in patients with heart failure. The investigators will also determine if BRJ improves blood pressure, exercise efficiency, vascular and muscle function, and whether blood levels of nitrates increase hourly for a total of 4 hours after BRJ ingestion. A secondary aim is to determine if BRJ-derived nitrates are still effective at 1, 2 and 4 weeks after starting treatment. A tertiary aim is to determine the variation in the 6 minute walk test. Subjects will answer a basic medical information sheet and undergo a 6-minute walk test. After at least a 48 hours rest, subjects will be asked to repeat the 6 minutes' walk. The investigators will (1) determine if BRJ (as compared to placebo) improves peak power output in heart failure patients and controls (at ~ 1½ to 2 hours after ingestion); (2) compare the changes in cardiac muscle (on average ~ 8-12 hours after) BRJ or placebo ingestion in patients who will be undergoing an left ventricle (LV) assist device placement for clinical purposes. (a cross-sectional study); (3) determine if BRJ decreases elevated pulmonary artery (PA) pressures or improves vascular and/or microvascular function (at ~ 1½ - 2 hours after ingestion) in patients who are already coming in for a PA catheter placement for clinical purposes; (4) compare the physiological changes after BRJ ingestion in non-heart failure control subjects with those of patients with heart failure. Endpoints measured at the same time points after ingestion. The investigators hypothesize (1) that patients with heart failure and controls will have improved exercise capacity and power at lower oxygen cost (and thereby greater efficiency) ~ 1½- 2 hours after ingesting beet juice (BRJ) than after ingesting placebo (beet juice without nitrates); (2) that patients with heart failure will have a greater physiologic response to BRJ than non-heart failure controls since the former have worse physiological function to start with; (3) that patients with high pulmonary artery pressures will have an improvement in the pressures after ingestion with BRJ; (4) that myocardial perfusion will be higher after BRJ ingestion than after placebo; (5) that cyclic guanosine monophosphate (cGMP) levels will be increased in left ventricle assist device (LVAD) samples after BRJ ingestion compared with placebo.
Detailed Description
For all studies and sub-studies:
A) All Subjects will be consented. B) All Subjects will give permission for the investigators to review their medical records.
For the BRJ main study (acute dose BRJ intervention):
- After consenting to participate, subjects will be instructed to refrain from spitting or the use of an antibacterial mouthwash, antacids, proton pump inhibitors, or chewing gum during the study.
- Subjects will be asked to answer questionnaires regarding their medical health (basic health questionnaire, Minnesota living with heart failure questionnaire, a magnetic resonance safety -i.e., questions regarding implanted pacemakers, etc...) 2a)Subjects will undergo a physical examination at one time during the study.
- Subjects will be interviewed by a dietician with regards to their typical dietary intake and instructed on a low nitrate diet.
- In study visit #1 subjects will be randomized to receive either a "shot" of BRJ (James White Drinks)or placebo (BRJ without nitrates).
- Before and at 3 time points (~hourly) after receiving the BRJ or placebo, subjects will undergo phlebotomy for plasma nutrient/hormone levels and will have their blood pressure checked. They will also be asked to swish (5 minutes) and spit out a dilute ~ 4tbps solution of nitrate,so we can quantify nitrate to nitrite conversion at ~ 1 1/4 hours after ingestion 5A) Subjects will undergo an echocardiogram just after the swish and spit.
- ~ 1 3/4 hours after ingestion, subjects will undergo a 6 minute walk.
- ~ 2 hours after ingestion, subjects will pedal an ergometer for 6 min at 15, 30, and 45 W (requiring ~50, ~60, and ~70% of oxygen consumption (VO2) peak, i.e., peak oxygen consumption) while VO2 is measured using a ParvoMedics TrueOne (this is the brand) metabolic cart. Five min of rest will be allowed between stages. The average VO2 during the last 2 min of each stage will be used to calculate gross and delta efficiency using stoichiometric equations as previously described. Following a 10 min rest period, peak power and VO2 peak will determined during a continuous exercise test performed using a 10 W/min ramp protocol.
- Subjects will then (immediately afterwards )undergo an Magnetic resonance (MR) study of skeletal muscle (and if there is time cardiac performance) with mild exercise (pushing one foot on a pedal for 6 min of submaximal isometric exercise (1 s contraction at 50% of previously-determined maximal voluntary contraction - according to their VO2 peak levels in their medical charts - every 9 s) with spectra acquired before, during, and after exercise.
During exercise, subjects will have their heart rate, blood pressure and rhythm monitored. 9. Subjects will be asked to undergo a mouth swab for bacterial DNA analyses (after the swish and spit) 9A) Subjects will undergo a Dual-energy Xray absorptiometry (DXA) scan for body composition analysis (either before or after BRJ ingestion - it is a phenotyping measure - not an endpoint) 10. Subjects will undergo a 7 d wash-out period 11. Subjects will come in for study day 2 in which they will receive whichever treatment (BRJ or placebo) that they did not receive at first and then repeat the studies listed above 5)-9).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and women will have a history of heart failure (and/or pulmonary hypertension for PA catheter substudy).
- •Age > or = 18 y and controls of the same age range without heart failure.
Exclusion Criteria
- •Age < 18 y.
- •Those taking phosphodiesterase inhibitors (e.g., Viagra) will be excluded, as these can potentiate NO effects.
- •Those taking proton pump inhibitors, antacids, or xanthine oxidase inhibitors will be excluded as these can affect reduction of nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO).
Outcomes
Primary Outcomes
Maximal Knee Extensor Power
Time Frame: 2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate
Maximal power of the quadriceps muscle group as measured using isokinetic dynamometry
Secondary Outcomes
- VO2peak(2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate)