Efficacy of Whole Extract of Licorice in Neurological Improvement of Patients After Acute Ischemic Stroke

Study Overview
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Brief Summary
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Stroke is one of the most important causes of mortality and disability both in developed and developing countries. The only food and drug administration (FDA) approved therapy for acute stroke is recombinant tissue plasminogen activator (rtPA). But narrow therapeutic window has limited the usefulness of thrombolytic therapy. Therefore, finding effective neuroprotective drugs for the patients for whom thrombolysis is contraindicated or not feasible seemed to be mandatory in the world of cerebrovascular medicine. Licorice, extracted from root of a plant scientifically known as Glycyrrhiza glabra, is used in food industries. Certain medical properties has been contributed to licorice and specifically to its active chemical components such as flavonoids and glycyrrhizic acid (GA). GA has been revealed to assert its anti-inflammatory effect by suppression of NF-κB, a key component of lipopolysaccharide-induced inflammatory response. Neuroprotective characteristics of GA has been widely investigated in recent studies. In the present study, the investigators verified the efficacy and safety of oral administration of two different doses licorice extract in the patients with acute ischemic stroke, in a double-blind randomized controlled trial.

Conditions
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Acute Stroke

Intervention / Treatment
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* Drug: Licorice whole extract
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of acute ischemic stroke ROSIER score higher than 2 Confirmation of ischemic brain damage in CT scan Exclusion Criteria: Clinically relevant preexisting neurological deficit or previous CVA Primary intracerebral hemorrhage Coma (level of consciousness more than 2 in NIHSS scale). Negative swallow test Patients undergoing hemicraniectomy History of epilepsy Clinical seizure at onset of stroke Systolic BP is >160 mmHg, diastolic BP>110 at onset of stroke (if a rise in blood pressure occurred in the course of study it was controlled according to medical guidelines) Atrial fibrillation or other tachy/bradyarrythmias at time of allocation or in the middle of intervention Ejection Fraction less than 45% Potassium less than 4 mEq/dl at onset of stroke Malignancy or premalignant state within 5 years Myocardial infarction in previous month Significant kidney disease (creatinine higher than 1.8 mg/dl) Significant liver disease (Bilirubin > 20 mmoll/L) Significant lung disease (FEV1 < 1.5 L, pO2 < 70 in room air, pCO2 > 45) Psychiatric illness requiring hospital admission Warfarin intake Digoxin intake Pregnancy Breast feeding Inability to have follow/up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control<br>patients with acute ischemic stroke who received standard care plus placebo filled capsules, | Drug: Placebo<br> <br> |
| Experimental: 450 mg licorice<br>patients with acute ischemic stroke who received standard care plus capsules filled with 450 mg of whole extract of licorice. | Drug: Licorice whole extract<br>* Patients randomly received one of below capsules labeled with codes during the first 24 hours after stroke attack: Starch-filled capsules (as placebo) 450 mg whole licorice extract capsules 900 mg whole licorice extract capsules<br>|
| Experimental: 900 mg licorice<br>patients with acute ischemic stroke who received standard care plus capsules filled with 900 mg of whole extract of licorice. | Drug: Licorice whole extract<br>* Patients randomly received one of below capsules labeled with codes during the first 24 hours after stroke attack: Starch-filled capsules (as placebo) 450 mg whole licorice extract capsules 900 mg whole licorice extract capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of neurological status of the patient measured by National Institute of health stroke Scale (NIHSS) after hospital stay | This scale is a standard measurement of neurological status of the patient | Atfer hospital stay, 5-14 days | 
| Change from baseline of neurological status of the patient measured by Modified Rankin Scale after hospital stay | This scale is a standard measurement of neurological status of the patient | Atfer hospital stay, 5-14 days | 
| Change from baseline of neurological status of the patient measured by National Institute of health stroke Scale (NIHSS) after 3 months |  | 3 months after stroke | 
| Change from baseline of neurological status of the patient measured by Modified Rankin Scale after 3 months |  | 3 months after stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood sugar | For measurement of possible hyperglycemic effect | Participants were followed during their hospital stay for an average duration of 5 days | 
| Blood pressure | For detection of possible of occurrence hypertension due to pseudo-hyperaldosteronism effect of licorice | Participants were followed during their hospital stay for an average duration of 5 days | 
| Serum Na and K | For detection of possible of occurrence hypertension due to pseudo-hyperaldosteronism effect of licorice | Participants were followed during their hospital stay for an average duration of 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Licorice, Glycyrrhizic acid, Ischemic Stroke, Acute