Dietary Nitrate Supplements and Ischemic Stroke Recovery

NCT ID: NCT02838901

Last Updated: 2018-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2016-06-30

Brief 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. 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.

Conditions

Stroke; Ischemic Stroke; Cerebrovascular Accident

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Beet It Beetroot Juice

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.

Group Type: EXPERIMENTAL

Beet it Beetroot juice

Intervention Type: DRUG

Concentrated organic beetroot (98%) and lemon juice (2%); 70ml bottle

Beet It Beetroot Juice Placebo

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.

Group Type: PLACEBO_COMPARATOR

Beet It Placebo Beetroot juice

Intervention Type: DRUG

Concentrated organic beetroot (98%) and lemon juice (2%) with nitrate extracted; 70ml bottle. Beet It Placebo Beetroot juice.

Interventions

Beet it Beetroot juice

Concentrated organic beetroot (98%) and lemon juice (2%); 70ml bottle

Intervention Type: DRUG

Beet It Placebo Beetroot juice

Concentrated organic beetroot (98%) and lemon juice (2%) with nitrate extracted; 70ml bottle. Beet It Placebo Beetroot juice.

Intervention Type: DRUG

Other Intervention Names

beetroot juice; beetroot juice placebo

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cheryl Bushnell, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest School of Medicine

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

IRB00020739

Identifier Type: -

Identifier Source: org_study_id