Dietary Nitrate Supplements and Ischemic Stroke Recovery

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.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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)

- 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