StrokePhase 2NCT02838901
Dietary Nitrate Supplements and Ischemic Stroke Recovery
A Phase 2 study testing Beet it Beetroot juice in people with Stroke and Ischemic Stroke, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
This is a double-blind, randomized, placebo-controlled, pilot study. Participants will be randomized to receive either beetroot juice or a beetroot juice placebo, as a dietary supplement, for 30 days. Beetroot juice is high in nitrates, a chemical when ingested is found to increase blood flow to the brain. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Ischemic Stroke, Cerebrovascular Accident
- What is being tested?
- Beet it Beetroot juice
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Jun 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years old and over
- Diagnosed with an ischemic stroke (acute focal neurological deficit resulting from an ischemic cause, verified by CT or MRI)
- Symptom onset within 5 days of admission
- National Institutes of Health Stroke Scale Score of 2 or more (but less than 20)
- A rating of fair or good on static sitting balance scale on a global balance scale
- A score of more that 0 on the hip flexion on the short Fugl-Myer
- Passed dysphagia screening for unrestricted or thickened liquids
Who cannot join
- Patients with severe stroke (National Institutes of Health Stroke Scale Score of 20 or more)
- A score of 0 on hip flexion on the Short Fugl-Myer as a result of weakness from the stroke
- A rating of poor on static sitting balance scale on a global balance scale
- Patients who received intravenous or intra-arterial recombinant tissue plasminogen activator (rtPA)
- Patients who are receiving citicoline
- Patients who have had a hemorrhagic stroke (including intraparenchymal, subarachnoid or subdural hemorrhage)
Show all 15Show fewer
- A gait speed of more > 0.8 m/s
- Patient with evidence of brain tumor or other psychiatric or neurological condition that would interfere with outcome measures
- Patients who will undergo carotid endarterectomy or other surgery during the study period
- Patients not living independently prior to stroke
- Survival is expected to be less than 6 months
- Any patient on organic nitrate-containing medications; some examples of the medications that are exclusions include nitroglycerin, isosorbide mononitrate, sildenafil (Viagra), and tadalafil (Cialis)
- Patients with atrophic gastritis
- Patients with hypotension (blood pressure less than 100/60 mmHg)
- Patients who do not pass the dysphagia screening test
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: Dietary Nitrate Supplements and Ischemic Stroke Recovery: A Pilot Study
This is a double-blind, randomized, placebo-controlled, pilot study. Participants will be randomized to receive either beetroot juice or a beetroot juice placebo, as a dietary supplement, for 30 days. Beetroot juice is high in nitrates, a chemical when ingested is found to increase blood flow to the brain. The purpose of this research study is to determine the safety and feasibility of using this nutritional intervention in (ischemic)stroke survivors, and prove that plasma levels of nitrate and nitrite increase as expected. Secondary outcomes includes measuring a comprehensive set of outcomes related to functional status post-stroke, including mobility, upper extremity strength, cognition, depression, and disability. Patients will also be randomized to MRI perfusion scanning in the region of the stroke to measure cerebral blood flow.
Read the detailed description
In this proof of concept study, the investigators will for the first time, determine whether dietary nitrate (commercially available beetroot juice) is safe and feasible to administer in ischemic stroke patients, and whether its use is associated with increased plasma nitrate and nitrite levels and trends toward improvement during the standard 30-day rehabilitation period after a stroke. The investigators will test the hypotheses using a double-blinded randomized placebo-controlled trial of Beet It® shots once daily for 30 days for patients enrolled within 5 days of stroke onset. This novel study will provide key safety and feasibility data on dietary nitrate supplementation and preliminary information on the magnitude of its effect on improving mobility and functional status, cognition and cerebral blood flow. These data are needed to accelerate the pace of development of this novel therapeutic strategy: using a non-pharmacological approach for improving stroke outcomes. The specific aims are to: Aim 1) Test the proof of concept that beetroot juice consumption is feasible and safe in ischemic stroke patients when given during the post-acute rehabilitation period. Primary outcomes are adherence to the intervention, measurement of outcomes and follow-up (feasibility), as well as adverse events (safety), reported as proportions in each group and across the entire study cohort. Hypothesis: Beetroot juice is safe and feasible in this population, and leads to increased plasma nitrate and nitrite levels at 30 days. Secondary outcomes of interest include change in gait speed (m/sec), Modified Rankin score (disability scale), NIHSS, EuroQOL-5D (quality of life),Patient Health Questionnaire-9 (depression), Stroke Impact Scale-16 (SIS-16), Barthel Index, Short Physical Performance Battery, grip strength and the Montreal Cognitive Assessment (MoCA). Aim 2) Determine whether beetroot juice consumption increases cerebral blood flow vs. placebo juice. Cerebral blood flow will be determined from MRI collected 2 hours following ingestion of the beetroot juice on day 30. Anatomic and perfusion imaging (PASL) will be performed. A region of interest will be used to measure blood flow in a 20mm sphere placed adjacent to the ischemic stroke and in the contralateral hemisphere. Hypothesis: Ischemic stroke patients randomized to the beetroot juice intervention will show increased cerebral blood flow as measured by MRI perfusion scanning in the region of the stroke compared with the placebo group at 30 days.
- Conditions
- Stroke, Ischemic Stroke, Cerebrovascular Accident
- Being tested
- Beet it Beetroot juice, Beet It Placebo Beetroot juice
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beet it Beetroot juiceDrug
Also called beetroot juice
Concentrated organic beetroot (98%) and lemon juice (2%); 70ml bottle
Beet It Placebo Beetroot juiceDrug
Also called beetroot juice placebo
Concentrated organic beetroot (98%) and lemon juice (2%) with nitrate extracted; 70ml bottle. Beet It Placebo Beetroot juice.
| Study group | Role | What they receive |
|---|---|---|
| Beet It Beetroot Juice | Experimental | 70 cc (3.8 millimoles nitrate) Beet It organic beetroot juice once a day for 30 days. Vitamin C 500 mg (tablets) will be given along with each dose of the juice. Receives: Drug: Beet it Beetroot juice |
| Beet It Beetroot Juice Placebo | Placebo comparator | 70 cc Beet It organic beetroot juice (placebo) once a day for 30 days. The placebo beet juice is identical in appearance and taste with nitrate removed. Vitamin C 500 mg (tablets) will be given along with each dose of the juice.Beet It Placebo Beetroot juice. Receives: Drug: Beet It Placebo Beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adherence With Intervention
The primary outcome for this trial is feasibility, which will be measured by how well the participants followed instructions on taking Beet It organic beetroot juice or placebo once a day for 30 days.
Measured: 30 days
Number of Participants With Adverse Treatment-altering Events
Adverse events that lead to treatment discontinuation
Measured: 30 days
Change in Plasma Nitrate Levels, Micromoles/Liter
This is the proof-of-concept to see if plasma levels change in those randomized to the active beet juice compared to placebo. Comparing baseline values against values at 30 days.
Measured: after 30 days of treatment
Change in Plasma Nitrite Levels, Micromoles/Liter
This is the proof-of-concept to see if plasma levels change in those randomized to the active beet juice compared to placebo. Comparing baseline values against values at 30 days.
Measured: after 30 days of treatment
Secondary outcomes (8)
Gait Speed Change From Baseline
Gait speed is measured by the time it takes to walk 10 meters. Baseline was reported.Change in gait speed from baseline was assessed at 30 and 90 days. Non-ambulatory at baseline is defined as gait speed less than 0.1 m/s.
Measured: baseline, 30, and 90 days
Cerebral Perfusion Imaging
Participants from each group who had an MRI at baseline will be randomly selected to have a repeat MRI perfusion scan at 30 days. Cerebral blood flow will be measured by MRI perfusion scanning (arterial spin labeling) in the region of the stroke.
Measured: 30 days
Upper Extremity Grip Strength
The hand grip strength test is designed to replicate the grip strength required to undertake officer survival and firearms training. The test is completed using a dynamometer which measures grip strength in kilograms (kg). The score ranges from 0-90kg, higher score denotes better outcomes.
Measured: 30 days
Upper Extremity Grip Strength
The hand grip strength test is designed to replicate the grip strength required to undertake officer survival and firearms training. The test is completed using a dynamometer which measures grip strength in kilograms. The score ranges from 0-90kg, higher score denotes better outcomes.
Measured: 90 days
Montreal Cognitive Assessment (MoCA) Score
Cognition is measured with the Montreal Cognitive Assessment. MoCA is a 30 question test that assesses different types of cognitive abilities, including orientation, short-term memory, executive function, language abilities, attention and visuospatial ability. Scores on the MoCA range from zero to 30, higher scores denotes better outcomes.
Measured: 30 days
Montreal Cognitive Assessment (MoCA) Score
Cognition is measured with the Montreal Cognitive Assessment. Cognition is measured with the Montreal Cognitive Assessment. MoCA is a 30 question test that assesses different types of cognitive abilities, including orientation, short-term memory, executive function, language abilities, attention and visuospatial ability. Scores on the MoCA range from zero to 30, higher scores denotes better outcomes.
Measured: 90 days
Modified Rankin Score
Modified Rankin Scale is a measure of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scores range from 0 (no symptoms) to 5 (bedridden in a nursing home). Lower scores denotes better outcomes.
Measured: 30 days
Modified Rankin Score
Modified Rankin Scale is a measure of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scores range from 0 (no symptoms) to 5 (bedridden in a nursing home). Lower scores denotes better outcomes.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2016 (estimated)
- Study startJun 2012
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cheryl Bushnell, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02838901
- Sponsor's protocol ID
- IRB00020739
- Status last verified
- Mar 2018
- First submitted
- 19 Jun 2016
- Last updated
- 10 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participants will be notified as to which arm of the study they were randomized to. The de-identified participant data will be presented as an abstract, if accepted, and published as a manuscript.
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Nitrate Supplements and Ischemic Stroke Recovery: A Pilot Study
- ClinicalTrials.gov ID
- NCT02838901
- Acronym / sponsor ID
- IRB00020739
- Conditions
- Stroke, Ischemic Stroke, Cerebrovascular Accident
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 20 Jul 2016 (estimated)
- Results
- Posted 10 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, randomized, placebo-controlled, pilot study. Participants will be randomized to receive either beetroot juice or a beetroot juice placebo, as a dietary supplement, for 30 days. Beetroot juice is high in nitrates, a chemical when ingested is found to increase blood flow to the brain. The purpose of this research study is to determine the safety and feasibility of using this nutritional intervention in (ischemic)stroke survivors, and prove that plasma levels of nitrate and nitrite increase as expected. Secondary outcomes includes measuring a comprehensive set of outcomes related to functional status post-stroke, including mobility, upper extremity strength, cognition, depression, and disability. Patients will also be randomized to MRI perfusion scanning in the region of the stroke to measure cerebral blood flow.
Detailed description
In this proof of concept study, the investigators will for the first time, determine whether dietary nitrate (commercially available beetroot juice) is safe and feasible to administer in ischemic stroke patients, and whether its use is associated with increased plasma nitrate and nitrite levels and trends toward improvement during the standard 30-day rehabilitation period after a stroke. The investigators will test the hypotheses using a double-blinded randomized placebo-controlled trial of Beet It® shots once daily for 30 days for patients enrolled within 5 days of stroke onset. This novel study will provide key safety and feasibility data on dietary nitrate supplementation and preliminary information on the magnitude of its effect on improving mobility and functional status, cognition and cerebral blood flow. These data are needed to accelerate the pace of development of this novel therapeutic strategy: using a non-pharmacological approach for improving stroke outcomes. The specific aims are to: Aim 1) Test the proof of concept that beetroot juice consumption is feasible and safe in ischemic stroke patients when given during the post-acute rehabilitation period. Primary outcomes are adherence to the intervention, measurement of outcomes and follow-up (feasibility), as well as adverse events (safety), reported as proportions in each group and across the entire study cohort. Hypothesis: Beetroot juice is safe and feasible in this population, and leads to increased plasma nitrate and nitrite levels at 30 days. Secondary outcomes of interest include change in gait speed (m/sec), Modified Rankin score (disability scale), NIHSS, EuroQOL-5D (quality of life),Patient Health Questionnaire-9 (depression), Stroke Impact Scale-16 (SIS-16), Barthel Index, Short Physical Performance Battery, grip strength and the Montreal Cognitive Assessment (MoCA). Aim 2) Determine whether beetroot juice consumption increases cerebral blood flow vs. placebo juice. Cerebral blood flow will be determined from MRI collected 2 hours following ingestion of the beetroot juice on day 30. Anatomic and perfusion imaging (PASL) will be performed. A region of interest will be used to measure blood flow in a 20mm sphere placed adjacent to the ischemic stroke and in the contralateral hemisphere. Hypothesis: Ischemic stroke patients randomized to the beetroot juice intervention will show increased cerebral blood flow as measured by MRI perfusion scanning in the region of the stroke compared with the placebo group at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Beet It Beetroot Juice | Experimental | Drug: Beet it Beetroot juice70 cc (3.8 millimoles nitrate) Beet It organic beetroot juice once a day for 30 days. Vitamin C 500 mg (tablets) will be given along with each dose of the juice. |
| Beet It Beetroot Juice Placebo | Placebo comparator | Drug: Beet It Placebo Beetroot juice70 cc Beet It organic beetroot juice (placebo) once a day for 30 days. The placebo beet juice is identical in appearance and taste with nitrate removed. Vitamin C 500 mg (tablets) will be given along with each dose of the juice.Beet It Placebo Beetroot juice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients 18 years old and over
- Diagnosed with an ischemic stroke (acute focal neurological deficit resulting from an ischemic cause, verified by CT or MRI)
- Symptom onset within 5 days of admission
- National Institutes of Health Stroke Scale Score of 2 or more (but less than 20)
- A rating of fair or good on static sitting balance scale on a global balance scale
Key exclusion criteria (15 listed)
- Patients with severe stroke (National Institutes of Health Stroke Scale Score of 20 or more)
- A score of 0 on hip flexion on the Short Fugl-Myer as a result of weakness from the stroke
- A rating of poor on static sitting balance scale on a global balance scale
- Patients who received intravenous or intra-arterial recombinant tissue plasminogen activator (rtPA)
- Patients who are receiving citicoline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Beet it Beetroot juiceAlso: beetroot juiceConcentrated organic beetroot (98%) and lemon juice (2%); 70ml bottle | Drug | Beet It Beetroot Juice |
| Beet It Placebo Beetroot juiceAlso: beetroot juice placeboConcentrated organic beetroot (98%) and lemon juice (2%) with nitrate extracted; 70ml bottle. Beet It Placebo Beetroot juice. | Drug | Beet It Beetroot Juice Placebo |
Primary outcome
Adherence With Intervention
Time frame: 30 days
The primary outcome for this trial is feasibility, which will be measured by how well the participants followed instructions on taking Beet It organic beetroot juice or placebo once a day for 30 days.
Number of Participants With Adverse Treatment-altering Events
Time frame: 30 days
Adverse events that lead to treatment discontinuation
Change in Plasma Nitrate Levels, Micromoles/Liter
Time frame: after 30 days of treatment
This is the proof-of-concept to see if plasma levels change in those randomized to the active beet juice compared to placebo. Comparing baseline values against values at 30 days.
Change in Plasma Nitrite Levels, Micromoles/Liter
Time frame: after 30 days of treatment
This is the proof-of-concept to see if plasma levels change in those randomized to the active beet juice compared to placebo. Comparing baseline values against values at 30 days.
8 secondary outcomes
Gait Speed Change From Baseline
Time frame: baseline, 30, and 90 days
Cerebral Perfusion Imaging
Time frame: 30 days
Upper Extremity Grip Strength
Time frame: 30 days
Upper Extremity Grip Strength
Time frame: 90 days
Montreal Cognitive Assessment (MoCA) Score
Time frame: 30 days
Montreal Cognitive Assessment (MoCA) Score
Time frame: 90 days
Modified Rankin Score
Time frame: 30 days
Modified Rankin Score
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Participants will be notified as to which arm of the study they were randomized to. The de-identified participant data will be presented as an abstract, if accepted, and published as a manuscript.
Related trials for Stroke
Recruiting
Connectomic Alterations Following Acute Ischemic Stroke in the MCA Territory
Ischemic Stroke
RecruitingObservational study
Clevidipine for the Antihypertensive Treatment of Acute Intracerebral Hemorrhage
Intracerebral Hemorrhage, Stroke
Active, not recruitingPhase 4
A Study Testing How Well the Drug Extract of Ginkgo Biloba Leaves Tablets Works for People With Memory or Thinking Problems After a Stroke When Added to Standard Treatment
Ischemic Stroke Hospitalized, Impairment, Cognitive
Not yet recruitingPhase 4
Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke
Ischemic Stroke
RecruitingObservational study
CoMind Early Feasibility Study
Intracranial Pressure, Intracranial Pressure Changes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cheryl Bushnell, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Beet it Beetroot juice in people with Stroke and Ischemic Stroke, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adherence With Intervention (time frame: 30 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2018.