Ischemic Stroke, Atherosclerosis
Conditions
Keywords
Ginseng, Stroke, Quantitative magnetic resonance flow analysis
Brief summary
This study is a 12-month, double-blind, randomized, placebo-controlled trial. The purpose of this study is to determine whether ginseng is effective in the prevention of atherosclerosis and subsequent ischemic stroke. High-risk patients with severe atherosclerosis in the major intracranial arteries and extracranial carotid artery were enrolled.
Interventions
DIETARY_SUPPLEMENTGinseng
Korean Red Ginseng extract tablet (0.5 grams/tablet, 2 tablets twice a day) daily for 12 months.
DIETARY_SUPPLEMENTPlacebo
Placebo (0.5 grams/tablet, 2 tablets twice a day) daily for 12 months.
Sponsors
Korea Ginseng Corporation
Dae Chul Suh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Patients were included if they 1. were aged 20 to 80 years; 2. had occlusion or severe stenosis (≥ 70%) of extracranial carotid artery and major intracranial arteries (intracranial carotid artery, middle cerebral artery, anterior cerebral artery, intracranial vertebral, basilar, or posterior cerebral artery) as documented by cerebral catheter angiography; 3. had any risk factor for stroke, such as hypertension, diabetes mellitus, hypercholesterolemia, smoking, alcohol drinking, or previous stroke history; 4. had no adverse reactions to administration of ginseng; and 5. agreed to participate in the trial.
Exclusion criteria
Patients were excluded if they 1. did not agree to participate in the trial; 2. had any genetic cerebrovascular diseases; 3. had adverse reactions to contrast medium; 4. were pregnant or planning to be pregnant; 5. had a history of cardioembolic stroke; 6. had an emboligenic cardiac disease such as atrial fibrillation, valve disease, congestive heart failure, or recent myocardial infarction; 7. had a risk of stroke of other determined etiology according to the TOAST classification; 8. had undergone any neurointervention procedure or surgery, such as intra-arterial thrombolysis, angioplasty procedures, carotid endarterectomy, or bypass surgery; 9. had chronic kidney disease (GFR \< 30 ml/min); or 10. had severe hepatic dysfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack | Twelve months after randomization. | The 1-year composite of cerebral ischemic stroke and transient ischemic attack downstream to an atherosclerotic lesion |
| Modified Rankin Scale | Twelve months after randomization. | Presence of other cerebro-cardiovascular morbidity or mortality assessed by aggravation of patient status (modified Rankin Scale). The modified Rankin Scale is ranging from 0 to 5. The higher scale indicates the worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | At randomization and twelve months after randomization. | The changes in volumetric blood flow (ml/sec) in intracranial vessels assessed by quantitative magnetic resonance angiography with noninvasive optimal vessel analysis. |
| The Changes of White Matter Hyperintensities. | At randomization and twelve months after randomization. | The changes of white matter hyperintensities, assessed by the Fazekas scale using brain magnetic resonance imaging. The Fazekas scale is a 4 point white matter disease severity scale with values ranging from 0 to 3. It quantifies the amount of white matter T2 hyperintense lesions each in periventricular white matter and deep white matter. Higher scales mean a worse white matter status. In the region of the periventricular white matter, 0 means absence of the lesion; 1, caps or pencil-thin lining lesion; 2, smooth halo lesion; 3, irregular high intense signal extending into the deep shite matter. In the region of the deep white matter, 0 means absence of the lesion; 1, punctate foci lesions; 2, beginning confluence; 3, large confluent hyperintense areas. |
| Number of Participants With Changes of Parenchymal Ischemic Lesions | At randomization and twelve months after randomization. | The changes of ischemic parenchymal lesions, assessed by brain magnetic resonance images acquired at randomization and twelve months after randomization. We counted the number of participants who had new ischemic parenchymal lesions at twelve months after randomization. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Drug Compliance | At twelve months after randomization. | We calculated average drug compliance based on the number of remained drugs at each follow-up. |
Countries
South Korea
Participant flow
Recruitment details
Patients in a single center, from June 2016 to June 2017.
Participants by arm
| Arm | Count |
|---|---|
| Ginseng Korean Red Ginseng extract tablet (0.5 grams/tablet, 2 tablets twice a day) daily for 12 months. | 28 |
| Placebo Placebo (0.5 grams/tablet, 2 tablets twice a day) daily for 12 months. | 24 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Noncompliance | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Placebo | Ginseng | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 13.6 | 63.4 years STANDARD_DEVIATION 12.5 | 60.3 years STANDARD_DEVIATION 13 |
| Alcohol drinking | 9 Participants | 6 Participants | 15 Participants |
| Angina pectoris | 2 Participants | 5 Participants | 7 Participants |
| Antidiabetic medication | 3 Participants | 9 Participants | 12 Participants |
| Antihyperlipidemic medication | 21 Participants | 25 Participants | 46 Participants |
| Antihypertensive medication | 13 Participants | 21 Participants | 34 Participants |
| Antiplatelet medication Dual antiplatelet | 14 Participants | 17 Participants | 31 Participants |
| Antiplatelet medication Mono antiplatelet | 9 Participants | 8 Participants | 17 Participants |
| Antiplatelet medication None | 0 Participants | 1 Participants | 1 Participants |
| Antiplatelet medication Other antiplatelet | 1 Participants | 2 Participants | 3 Participants |
| Atrial fibrillation | 0 Participants | 0 Participants | 0 Participants |
| Baseline modified Rankin Scale (mRS) mRS 0 | 22 Participants | 21 Participants | 43 Participants |
| Baseline modified Rankin Scale (mRS) mRS 1 | 1 Participants | 5 Participants | 6 Participants |
| Baseline modified Rankin Scale (mRS) mRS 2 | 0 Participants | 0 Participants | 0 Participants |
| Baseline modified Rankin Scale (mRS) mRS 3 | 1 Participants | 2 Participants | 3 Participants |
| Baseline modified Rankin Scale (mRS) mRS 4 | 0 Participants | 0 Participants | 0 Participants |
| Baseline modified Rankin Scale (mRS) mRS 5 | 0 Participants | 0 Participants | 0 Participants |
| Diabetes mellitus | 4 Participants | 10 Participants | 14 Participants |
| Hyperlipidemia | 15 Participants | 23 Participants | 38 Participants |
| Hypertension | 14 Participants | 20 Participants | 34 Participants |
| Myocardial infarction | 0 Participants | 0 Participants | 0 Participants |
| Previous stroke history | 9 Participants | 13 Participants | 22 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment South Korea | 24 Participants | 28 Participants | 52 Participants |
| Sex: Female, Male Female | 8 Participants | 13 Participants | 21 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
| Smoking | 13 Participants | 5 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 1 / 29 |
| other Total, other adverse events | 1 / 29 | 2 / 29 |
| serious Total, serious adverse events | 0 / 29 | 1 / 29 |
Outcome results
Primary
Modified Rankin Scale
Presence of other cerebro-cardiovascular morbidity or mortality assessed by aggravation of patient status (modified Rankin Scale). The modified Rankin Scale is ranging from 0 to 5. The higher scale indicates the worse outcome.
Time frame: Twelve months after randomization.
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ginseng | Modified Rankin Scale | mRS 0 | 21 Participants |
| Ginseng | Modified Rankin Scale | mRS 1 | 5 Participants |
| Ginseng | Modified Rankin Scale | mRS 2 | 0 Participants |
| Ginseng | Modified Rankin Scale | mRS 3 | 2 Participants |
| Ginseng | Modified Rankin Scale | mRS 4 | 0 Participants |
| Ginseng | Modified Rankin Scale | mRS 5 | 0 Participants |
| Placebo | Modified Rankin Scale | mRS 4 | 0 Participants |
| Placebo | Modified Rankin Scale | mRS 0 | 22 Participants |
| Placebo | Modified Rankin Scale | mRS 3 | 1 Participants |
| Placebo | Modified Rankin Scale | mRS 1 | 1 Participants |
| Placebo | Modified Rankin Scale | mRS 5 | 0 Participants |
| Placebo | Modified Rankin Scale | mRS 2 | 0 Participants |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and modified Rankin Scale at follow-up.p-value: 0.34Fisher Exact
Primary
The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack
The 1-year composite of cerebral ischemic stroke and transient ischemic attack downstream to an atherosclerotic lesion
Time frame: Twelve months after randomization.
Population: Full analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ginseng | The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack | Ischemic stroke | 0 Participants |
| Ginseng | The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack | Transient ischemic attack | 0 Participants |
| Placebo | The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack | Ischemic stroke | 0 Participants |
| Placebo | The Composite of Cerebral Ischemic Stroke and Transient Ischemic Attack | Transient ischemic attack | 1 Participants |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and cerebral ischemic events including ischemic stroke and transient ischemic attack. The number of participants who suffered ischemic stroke and the number of paticipants who suffered transient ischemic attack were analyzed together to test the null hypothesis in two by two table.p-value: 0.462Fisher Exact
Secondary
Number of Participants With Changes of Parenchymal Ischemic Lesions
The changes of ischemic parenchymal lesions, assessed by brain magnetic resonance images acquired at randomization and twelve months after randomization. We counted the number of participants who had new ischemic parenchymal lesions at twelve months after randomization.
Time frame: At randomization and twelve months after randomization.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ginseng | Number of Participants With Changes of Parenchymal Ischemic Lesions | Ischemic lesion (+) | 22 Participants |
| Ginseng | Number of Participants With Changes of Parenchymal Ischemic Lesions | Ischemic lesion (-) | 6 Participants |
| Placebo | Number of Participants With Changes of Parenchymal Ischemic Lesions | Ischemic lesion (+) | 15 Participants |
| Placebo | Number of Participants With Changes of Parenchymal Ischemic Lesions | Ischemic lesion (-) | 9 Participants |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and parenchymal ischemic lesions at follow-up.p-value: 0.23Chi-squared
Secondary
The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels.
The changes in volumetric blood flow (ml/sec) in intracranial vessels assessed by quantitative magnetic resonance angiography with noninvasive optimal vessel analysis.
Time frame: At randomization and twelve months after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | Aggravated | 4 Participants |
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | Improved | 4 Participants |
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | Improved | 7 Participants |
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | No change | 17 Participants |
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | No change | 17 Participants |
| Ginseng | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | Aggravated | 7 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | Aggravated | 8 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | No change | 18 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | Aggravated | 1 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | No change | 9 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in collateral vessel | Improved | 7 Participants |
| Placebo | The Changes in Volumetric Blood Flow (ml/Sec) in Intracranial Vessels. | The flow change in steno-occlusive lesion | Improved | 5 Participants |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and flow change in steno-occlusive lesion.p-value: 0.13Fisher Exact
Comparison: The null hypothesis is that there is no relationship between ginseng administration and flow change in collateral vessel.p-value: 0.17Chi-squared
Secondary
The Changes of White Matter Hyperintensities.
The changes of white matter hyperintensities, assessed by the Fazekas scale using brain magnetic resonance imaging. The Fazekas scale is a 4 point white matter disease severity scale with values ranging from 0 to 3. It quantifies the amount of white matter T2 hyperintense lesions each in periventricular white matter and deep white matter. Higher scales mean a worse white matter status. In the region of the periventricular white matter, 0 means absence of the lesion; 1, caps or pencil-thin lining lesion; 2, smooth halo lesion; 3, irregular high intense signal extending into the deep shite matter. In the region of the deep white matter, 0 means absence of the lesion; 1, punctate foci lesions; 2, beginning confluence; 3, large confluent hyperintense areas.
Time frame: At randomization and twelve months after randomization.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ginseng | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 1 | 9 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 0 | 9 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 2 | 15 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 3 | 2 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 1 | 15 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 3 | 1 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 0 | 2 Participants |
| Ginseng | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 2 | 3 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 1 | 11 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 3 | 2 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 0 | 6 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 2 | 2 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 3 | 1 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 2 | 10 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Deep white matter | Fazekas scale 1 | 15 Participants |
| Placebo | The Changes of White Matter Hyperintensities. | Periventricular white matter | Fazekas scale 0 | 1 Participants |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and periventricular white matter lesions at follow-up.p-value: 0.74Fisher Exact
Comparison: The null hypothesis is that there is no relationship between ginseng administration and deep white matter lesions at follow-up.p-value: 0.95Fisher Exact
Other Pre-specified
Drug Compliance
We calculated average drug compliance based on the number of remained drugs at each follow-up.
Time frame: At twelve months after randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ginseng | Drug Compliance | 97.4 percentage of drug compliance | Standard Deviation 4.7 |
| Placebo | Drug Compliance | 97.8 percentage of drug compliance | Standard Deviation 4.3 |
Comparison: The null hypothesis is that there is no relationship between ginseng administration and drug compliance at follow-up.p-value: 0.79Wilcoxon (Mann-Whitney)