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CompletedNCT01682356Updated Dec 4, 2024Results posted

Dietary Nitrate for Heart Failure

A Phase 1/2 interventional study of Beetroot juice in Heart Failure and Hypertension, Pulmonary, sponsored by Washington University School of Medicine. Completed at 2 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-04.

Sponsored by Washington University School of Medicine · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
17
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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):

  1. 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.
  2. 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.
  3. Subjects will be interviewed by a dietician with regards to their typical dietary intake and instructed on a low nitrate diet.
  4. In study visit #1 subjects will be randomized to receive either a "shot" of BRJ (James White Drinks)or placebo (BRJ without nitrates).
  5. 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.
  6. \~ 1 3/4 hours after ingestion, subjects will undergo a 6 minute walk.
  7. \~ 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.

  8. 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).

(The total time of the study is estimated to take 5 hours)

For the longer 2 (or 4) week BRJ substudy: (subjects include HF (heart failure) patients and nonHF controls, i.e., those without heart failure)

  1. Subjects will be asked to undergo steps 1-9 above, ingest 1 week of BRJ (1 "shot"/day) and then undergo the studies listed 5)-9).
  2. Subjects will be asked to ingest 1 more week of BRJ (1 "shot"/day for a total of 2 weeks) and then undergo a repeat of studies listed 5)-9)

For the BRJ neuromuscular function testing sub-study:

  1. Subjects will be asked to undergo steps 1-6 above
  2. Subjects will be asked to undergo a mouth swab for bacterial DNA analyses.
  3. Subjects will undergo a test of neuromuscular function using an isokinetic dynamometer (a device that measures voluntary muscle force production while controlling the speed of movement) immediately after the echocardiogram at \~2 h after BRJ (or placebo ingestion).

3A) Subjects will be asked to undergo an optional skeletal muscle biopsy immediately after the Biodex study.

3B) Subjects will undergo a dual-energy isokinetic dynamometry study for body composition analysis (at any time point during the study day).

  1. Subjects will undergo a 7 d washout period.
  1. Subjects will come in for Study day 2 in which they will receive whichever treatment (BRJ or placebo) they did not receive at first and then repeat the studies listed above 1-3.

For the Pulmonary artery (PA) pressure sub-study:

NOTE: This study will only be performed in patients who are undergoing a PA catheter placement for clinical purposes (high PA pressures) anyway.

  1. 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.
  2. Subjects will be asked to answer questionnaires regarding their medical health (basic health questionnaire, Minnesota living with heart failure questionnaire, etc.) 2a) Subjects will be asked to undergo a physical examination.
  3. Before and at 3 (hourly) time points after receiving a "shot" of BRJ, subjects will undergo phlebotomy for plasma nutrient/hormone levels and will have their blood pressure checked and will blow into a tube connected to a small machine that will measure the amount of nitric oxide in their breath. Subjects will also have cardiovascular measurements (e.g., cardiac output, PA pressure, etc.) made before and at 3 \~ hourly time points after receiving the BRJ. These measurements will be made using a PA catheter that is being placed for clinical purposes.
  4. If a subject is to undergo an LVAD placement he/she will be randomized to receive BRJ or placebo the evening before surgery (anticipated average \~ 8-12 hours before), and then the LV core will be harvested and immediately frozen for later analysis.
  5. Subjects who will be undergoing myocardial perfusion studies will undergo the same basic studies (breath NO, plasma nitrate/nitrite determination, as mentioned in the neuromuscular aim, but subjects will also undergo a positron emission tomography (PET) study in which they will receive O-15 water for quantification of myocardial blood flow \~ 2 hours after consumption of BRJ or placebo. Then they will undergo a washout phase of 7 d and then repeat the PET study after the other treatment (BRJ or placebo).
02

Conditions studied

  • Heart Failure
  • Hypertension, Pulmonary

Keywords

  • heart failure
  • hypertension, pulmonary
  • oxygen consumption
  • exercise tolerance
03

In context

Hypertension, Pulmonary

1,105 studies on the registry are indexed under Hypertension, Pulmonary; 234 are open to participants now.

This study's enrollment of 17 is below the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.

Browse Hypertension, Pulmonary studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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).
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
17 participants (actual)

Study arms

  • Placebo comparator
    Beetroot juice without nitrate

    Patients will be studied before and after ingestion of beetroot juice without nitrate

    Dietary Supplement: Beetroot juice

  • Active comparator
    Beetroot juice with nitrate

    Patients will be studied before and after ingestion of beetroot juice with nitrate.

    Dietary Supplement: Beetroot juice

Interventions

  • Dietary supplementBeetroot juice

    double-blind placebo-controlled cross-over study

    Also known as: Beet It

06

What researchers measure

Primary outcomes

  1. Maximal Knee Extensor Power

    Maximal power of the quadriceps muscle group as measured using isokinetic dynamometry

    Time frame: 2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate

Secondary outcomes

  1. VO2peak

    Peak oxygen consumption as measured during semi-recumbent cycle ergometer exercise

    Time frame: 2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate

Other outcomes

  1. Baseline Plasma Nitrate

    Nitrate in plasma before ingestion of beetroot juice

    Time frame: 0 h

  2. Plasma Nitrate @ 1 h

    Nitrate in plasma 1 h after ingestion of beetroot juice

    Time frame: 1 h

  3. Plasma Nitrate @ 2 h

    Nitrate in plasma 2 h after ingestion of beetroot juice

    Time frame: 2 h

  4. Plasma Nitrate @ 10 Min Post-exercise

    Nitric oxide in breath 10 min after completion of exercise testing

    Time frame: 10 min post-exercise

  5. Baseline Plasma Nitrite

    Nitrite in plasma before ingestion of beetroot juice

    Time frame: 0 h

  6. Plasma Nitrite @ 1 h

    Nitrite in plasma 1 h after ingestion of beetroot juice

    Time frame: 1 h

  7. Plasma Nitrite @ 2 h

    Nitrite in plasma 1 h after ingestion of beetroot juice

    Time frame: 2 h

  8. Plasma Nitrite @ 10 Min Post-exercise

    Nitrite in plasma 10 min after completion of exercise testing

    Time frame: 10 min post-exercise

  9. Baseline Breath Nitric Oxide

    Nitric oxide in breath before ingestion of beetroot juice

    Time frame: 0 h

  10. Breath Nitric Oxide @ 1 h

    Nitric oxide in breath 1 h after ingestion of beetroot juice

    Time frame: 1 h

  11. Breath Nitric Oxide @ 2 h

    Nitric oxide in breath 2 h after ingestion of beetroot juice

    Time frame: 2 h

  12. Breath Nitric Oxide @ 10 Min Post-exercise

    Nitric oxide in breath 10 min after completion of exercise testing

    Time frame: 10 min post

  13. Baseline Systolic Blood Pressure

    Systolic blood pressure before ingestion of beetroot juice

    Time frame: 0 h

  14. Systolic Blood Pressure @ 1 h

    Systolic blood pressure 1 h after ingestion of beetroot juice

    Time frame: 1 h

  15. Systolic Blood Pressure @ 2 h

    Systolic blood pressure 2 h after ingestion of beetroot juice

    Time frame: 2 h

  16. Systolic Blood Pressure @ 10 Min Post-exercise

    Systolic blood pressure 10 min after completion of exercise testing

    Time frame: 10 min post-exercise

  17. Baseline Diastolic Blood Pressure

    Diastolic blood pressure before ingestion of beetroot juice

    Time frame: 0 h

  18. Diastolic Blood Pressure @ 1 h

    Diastolic blood pressure 1 h after ingestion of beetroot juice

    Time frame: 1 h

  19. Diastolic Blood Pressure @ 2 h

    Diastolic blood pressure 2 h after ingestion of beetroot juice

    Time frame: 2 h

  20. Diastolic Blood Pressure @ 10 Min Post-exercise

    Diastolic blood pressure 10 min after completion of exercise testing

    Time frame: 10 min post-exercise

  21. Cardiac Function

    Subjects undergoing MRI or echocardiography will have various measures of cardiac function made

    Time frame: after ingestion of BRJ or placebo

  22. Pulmonary Artery Pressure

    Each patient who is going to have a PA catheter placed for clinical purposes will have their PA pressures measured before and after ingestion of BRJ.

    Time frame: 1 day intervention

  23. Vascular Function

    Each subject undergoes a laser Doppler test and a brachial artery test after ingesting BRJ or placebo. There is a 10 d washout period and then the test is repeated after the subject ingests the BRJ or placebo (whichever was not taken the first time).

    Time frame: each patient will undergo a study for a maximum of ~ 2 weeks

  24. Myocardial Perfusion

    We will measure perfusion using noninvasive PET imaging

    Time frame: before and after BRJ or placebo ingestion

  25. Myocardial Tissue Changes

    We will measure cyclic GMP and nitrate in LV tissue after LVAD placement and after ingestion of either BRJ or placebo

    Time frame: after BRJ or placebo ingestion

07

Results

Posted Dec 4, 2024
Limitations and caveats
Due to restrictions on research resulting from the COVID-19 pandemic, many outcome measures/planned substudies were not completed.

Participant flow

Participant flow — Overall Study
MilestonePlacebo Then NitrateNitrate Then Placebo
Started107
Completed107
Not completed00

Outcome measures

PrimaryMaximal Knee Extensor Power

Maximal power of the quadriceps muscle group as measured using isokinetic dynamometry

Time frame:
2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate
Reported as:
Mean · W/kg
Maximal Knee Extensor Power
W/kgPlaceboNitrate
Maximal Knee Extensor Power4.20 ± 0.334.74 ± 0.41
Statistical analysis
  • Placebo vs Nitrate · t-test, 2 sided · p = 0.0153Paired
SecondaryVO2peak

Peak oxygen consumption as measured during semi-recumbent cycle ergometer exercise

Time frame:
2-3 h after acute dose of beetroot juice containing or essentially devoid of nitrate
Reported as:
Mean · mL/min/kg
VO2peak
mL/min/kgPlaceboNitrate
VO2peak21.4 ± 2.123.0 ± 2.3
Statistical analysis
  • Placebo vs Nitrate · t-test, 2 sided · p = 0.0131Paired
Other pre-specifiedBaseline Plasma Nitrate

Nitrate in plasma before ingestion of beetroot juice

Time frame:
0 h
Reported as:
Mean · umol/L
Baseline Plasma Nitrate
umol/LPlaceboNitrate
Baseline Plasma Nitrate27 ± 431 ± 4
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.83 (P value adjusted for multiplicity)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrate @ 1 h

Nitrate in plasma 1 h after ingestion of beetroot juice

Time frame:
1 h
Reported as:
Mean · umol/L
Plasma Nitrate @ 1 h
umol/LPlaceboNitrate
Plasma Nitrate @ 1 h25 ± 3334 ± 31
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = <0.0000001 (P values adjusted for multiplicity. Exact P value 6.06 x 10\^-18.)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrate @ 2 h

Nitrate in plasma 2 h after ingestion of beetroot juice

Time frame:
2 h
Reported as:
Mean · umol/L
Plasma Nitrate @ 2 h
umol/LPlaceboNitrate
Plasma Nitrate @ 2 h24 ± 3386 ± 172
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = <0.0000001 (P values adjusted for multiplicity. Exact P value 1.87 x 10\^-20.)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrate @ 10 Min Post-exercise

Nitric oxide in breath 10 min after completion of exercise testing

Time frame:
10 min post-exercise
Reported as:
Mean · umol/L
Plasma Nitrate @ 10 Min Post-exercise
umol/LPlaceboNitrate
Plasma Nitrate @ 10 Min Post-exercise25 ± 3397 ± 45
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = <0.0000001 (P values adjusted for multiplicity. Exact P value 8.23 x 10\^-21.)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBaseline Plasma Nitrite

Nitrite in plasma before ingestion of beetroot juice

Time frame:
0 h
Reported as:
Mean · umol/L
Baseline Plasma Nitrite
umol/LPlaceboNitrate
Baseline Plasma Nitrite0.292 ± 0.0700.341 ± 0.146
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.6847 (P values adjusted for multiplicity)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrite @ 1 h

Nitrite in plasma 1 h after ingestion of beetroot juice

Time frame:
1 h
Reported as:
Mean · umol/L
Plasma Nitrite @ 1 h
umol/LPlaceboNitrate
Plasma Nitrite @ 1 h0.254 ± 0.0640.298 ± 0.085
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.6847 (P values adjusted for multiplicity)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrite @ 2 h

Nitrite in plasma 1 h after ingestion of beetroot juice

Time frame:
2 h
Reported as:
Mean · umol/L
Plasma Nitrite @ 2 h
umol/LPlaceboNitrate
Plasma Nitrite @ 2 h0.216 ± 0.0500.315 ± 0.059
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.4078 (P values adjusted for multiplicity)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedPlasma Nitrite @ 10 Min Post-exercise

Nitrite in plasma 10 min after completion of exercise testing

Time frame:
10 min post-exercise
Reported as:
Mean · umol/L
Plasma Nitrite @ 10 Min Post-exercise
umol/LPlaceboNitrate
Plasma Nitrite @ 10 Min Post-exercise0.306 ± 0.0830.400 ± 0.093
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.4078 (P values adjusted for multiplicity)Plasma nitrate values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBaseline Breath Nitric Oxide

Nitric oxide in breath before ingestion of beetroot juice

Time frame:
0 h
Reported as:
Mean · ppm
Baseline Breath Nitric Oxide
ppmPlaceboNitrate
Baseline Breath Nitric Oxide18 ± 120 ± 2
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.3042 (P value adjusted for multiplicity)Breath nitric oxide values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBreath Nitric Oxide @ 1 h

Nitric oxide in breath 1 h after ingestion of beetroot juice

Time frame:
1 h
Reported as:
Mean · ppm
Breath Nitric Oxide @ 1 h
ppmPlaceboNitrate
Breath Nitric Oxide @ 1 h19 ± 229 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = <0.0000001 (P value adjusted for multiplicity. Exact P value 3.469 x 10\^-7.)Breath nitric oxide values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBreath Nitric Oxide @ 2 h

Nitric oxide in breath 2 h after ingestion of beetroot juice

Time frame:
2 h
Reported as:
Mean · ppm
Breath Nitric Oxide @ 2 h
ppmPlaceboNitrate
Breath Nitric Oxide @ 2 h19 ± 231 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = <0.0000001 (P value adjusted for multiplicity. Exact P value 7.202 x 10\^-8)Breath nitric oxide values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBreath Nitric Oxide @ 10 Min Post-exercise

Nitric oxide in breath 10 min after completion of exercise testing

Time frame:
10 min post
Reported as:
Mean · ppm
Breath Nitric Oxide @ 10 Min Post-exercise
ppmPlaceboNitrate
Breath Nitric Oxide @ 10 Min Post-exercise17 ± 127 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.00000213 (P value adjusted for multiplicity. Exact P value 2.129 x 10\^-6.)Breath nitric oxide values were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBaseline Systolic Blood Pressure

Systolic blood pressure before ingestion of beetroot juice

Time frame:
0 h
Reported as:
Mean · mmHg
Baseline Systolic Blood Pressure
mmHgPlaceboNitrate
Baseline Systolic Blood Pressure106 ± 4109 ± 4
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.3918 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedSystolic Blood Pressure @ 1 h

Systolic blood pressure 1 h after ingestion of beetroot juice

Time frame:
1 h
Reported as:
Mean · mmHg
Systolic Blood Pressure @ 1 h
mmHgPlaceboNitrate
Systolic Blood Pressure @ 1 h104 ± 4109 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.05980 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedSystolic Blood Pressure @ 2 h

Systolic blood pressure 2 h after ingestion of beetroot juice

Time frame:
2 h
Reported as:
Mean · mmHg
Systolic Blood Pressure @ 2 h
mmHgPlaceboNitrate
Systolic Blood Pressure @ 2 h104 ± 3106 ± 4
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.3918 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedSystolic Blood Pressure @ 10 Min Post-exercise

Systolic blood pressure 10 min after completion of exercise testing

Time frame:
10 min post-exercise
Reported as:
Mean · mmHg
Systolic Blood Pressure @ 10 Min Post-exercise
mmHgPlaceboNitrate
Systolic Blood Pressure @ 10 Min Post-exercise111 ± 4106 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.09870 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedBaseline Diastolic Blood Pressure

Diastolic blood pressure before ingestion of beetroot juice

Time frame:
0 h
Reported as:
Mean · mmHg
Baseline Diastolic Blood Pressure
mmHgPlaceboNitrate
Baseline Diastolic Blood Pressure68 ± 371 ± 3
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.6044 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedDiastolic Blood Pressure @ 1 h

Diastolic blood pressure 1 h after ingestion of beetroot juice

Time frame:
1 h
Reported as:
Mean · mmHg
Diastolic Blood Pressure @ 1 h
mmHgPlaceboNitrate
Diastolic Blood Pressure @ 1 h66 ± 368 ± 2
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.6044 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedDiastolic Blood Pressure @ 2 h

Diastolic blood pressure 2 h after ingestion of beetroot juice

Time frame:
2 h
Reported as:
Mean · mmHg
Diastolic Blood Pressure @ 2 h
mmHgPlaceboNitrate
Diastolic Blood Pressure @ 2 h67 ± 368 ± 2
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.8819 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedDiastolic Blood Pressure @ 10 Min Post-exercise

Diastolic blood pressure 10 min after completion of exercise testing

Time frame:
10 min post-exercise
Reported as:
Mean · mmHg
Diastolic Blood Pressure @ 10 Min Post-exercise
mmHgPlaceboNitrate
Diastolic Blood Pressure @ 10 Min Post-exercise69 ± 369 ± 2
Statistical analysis
  • Placebo vs Nitrate · ANOVA · p = 0.8987 (P values adjusted for multiplicity)Values for blood pressure were analyzed using a repeated measures ANOVA followed by Holm-Šídák multiple comparison testing
Other pre-specifiedCardiac Function

Subjects undergoing MRI or echocardiography will have various measures of cardiac function made

Time frame:
after ingestion of BRJ or placebo

Results for this outcome have not been posted.

Other pre-specifiedPulmonary Artery Pressure

Each patient who is going to have a PA catheter placed for clinical purposes will have their PA pressures measured before and after ingestion of BRJ.

Time frame:
1 day intervention

Results for this outcome have not been posted.

Other pre-specifiedVascular Function

Each subject undergoes a laser Doppler test and a brachial artery test after ingesting BRJ or placebo. There is a 10 d washout period and then the test is repeated after the subject ingests the BRJ or placebo (whichever was not taken the first time).

Time frame:
each patient will undergo a study for a maximum of ~ 2 weeks

Results for this outcome have not been posted.

Other pre-specifiedMyocardial Perfusion

We will measure perfusion using noninvasive PET imaging

Time frame:
before and after BRJ or placebo ingestion

Results for this outcome have not been posted.

Other pre-specifiedMyocardial Tissue Changes

We will measure cyclic GMP and nitrate in LV tissue after LVAD placement and after ingestion of either BRJ or placebo

Time frame:
after BRJ or placebo ingestion

Results for this outcome have not been posted.

Adverse events

Collected over One day per intervention with 7 days of washout in between. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/17 (0%)0/17 (0%)0/17 (0%)
Nitrate0/17 (0%)0/17 (0%)0/17 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Placebo Then NitrateNitrate Then PlaceboTotal
Mean53 ± 1257 ± 1255 ± 12
Sex: Female, Male
Sex: Female, Male(Participants)Placebo Then NitrateNitrate Then PlaceboTotal
Female426
Male6511
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo Then NitrateNitrate Then PlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American112
White9615
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Placebo Then NitrateNitrate Then PlaceboTotal
United States10717
08

Study locations

2 sites
  • Indiana University Purdue University Indianapolis
    Indianapolis, Indiana 46202, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
09

References and documents

Publications

  • Masschelein E, Van Thienen R, Wang X, Van Schepdael A, Thomis M, Hespel P. Dietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxia. J Appl Physiol (1985). 2012 Sep 1;113(5):736-45. doi: 10.1152/japplphysiol.01253.2011. Epub 2012 Jul 5. PubMed 22773768 ↗
  • Hobbs DA, Kaffa N, George TW, Methven L, Lovegrove JA. Blood pressure-lowering effects of beetroot juice and novel beetroot-enriched bread products in normotensive male subjects. Br J Nutr. 2012 Dec 14;108(11):2066-74. doi: 10.1017/S0007114512000190. Epub 2012 Mar 14. PubMed 22414688 ↗
  • Cermak NM, Gibala MJ, van Loon LJ. Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exerc Metab. 2012 Feb;22(1):64-71. doi: 10.1123/ijsnem.22.1.64. PubMed 22248502 ↗
  • Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AM. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J Physiol. 2011 Nov 15;589(Pt 22):5517-28. doi: 10.1113/jphysiol.2011.216341. Epub 2011 Sep 12. PubMed 21911616 ↗
  • Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol (1985). 2011 Jun;110(6):1582-91. doi: 10.1152/japplphysiol.00071.2011. Epub 2011 Mar 31. PubMed 21454745 ↗
  • Ferreira LF, Behnke BJ. A toast to health and performance! Beetroot juice lowers blood pressure and the O2 cost of exercise. J Appl Physiol (1985). 2011 Mar;110(3):585-6. doi: 10.1152/japplphysiol.01457.2010. Epub 2010 Dec 23. No abstract available. PubMed 21183624 ↗
  • Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AM. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol. 2010 Oct;299(4):R1121-31. doi: 10.1152/ajpregu.00206.2010. Epub 2010 Aug 11. PubMed 20702806 ↗
  • Wilkerson DP, Hayward GM, Bailey SJ, Vanhatalo A, Blackwell JR, Jones AM. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists. Eur J Appl Physiol. 2012 Dec;112(12):4127-34. doi: 10.1007/s00421-012-2397-6. Epub 2012 Apr 20. PubMed 22526247 ↗
  • Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol (1985). 2009 Oct;107(4):1144-55. doi: 10.1152/japplphysiol.00722.2009. Epub 2009 Aug 6. PubMed 19661447 ↗
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  • Coggan AR, Leibowitz JL, Spearie CA, Kadkhodayan A, Thomas DP, Ramamurthy S, Mahmood K, Park S, Waller S, Farmer M, Peterson LR. Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial. Circ Heart Fail. 2015 Sep;8(5):914-20. doi: 10.1161/CIRCHEARTFAILURE.115.002141. Epub 2015 Jul 15. PubMed 26179185 ↗

Study documents

  • Study protocol · Dec 7, 2023
  • Statistical analysis plan · Dec 7, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Aggregate data that contains no HIPPA identifiers will be made available as required if the request complies with all federal and University policies for data sharing. IPD will not be shared since this is a small study at a single institution, so the likelihood of identifying subjects would be increased.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 4, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01682356
Lead sponsor
Washington University School of Medicine
Collaborators
The Foundation for Barnes-Jewish Hospital
Responsible party
Sponsor
First posted
Sep 10, 2012
Start date
Jan 2012
Primary completion
Jul 1, 2023
Completion
Jul 1, 2023
Results posted
Dec 4, 2024
Last update
Dec 4, 2024

Study contacts

Linda R Peterson, MD
principal investigator · Washington University School of Medicine
Andrew R Coggan, PhD
principal investigator · Indiana University School of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.

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