NCT ID: NCT00059306
Principal Investigator: Oscar Benavente, M.D.
The goal of this study is to learn if combination antiplatelet therapy (aspirin and clopidogrel) is more effective than aspirin alone for the prevention of recurrent stroke and cognitive decline, and if intensive blood pressure control is associated with fewer recurrent strokes and cognitive decline. On July 21, 2011 the DSMB recommended terminating the anti platelet arm of the study due to an imbalance of overall and major non-CNS hemorrhagic SAE's and total deaths in the investigational anti platelet combination of aspirin + clopidogrel and an interim statistical analysis that demonstrated futility in the investigational anti platelet arm. It was recommended that patients be continued on standard care of aspirin mono therapy until their study close-out visit. Also, recommended the continuation and completion of the plood pressure arm following the protocol.
Stroke is damage to the brain caused by problems in the blood vessels. Strokes often cause paralysis, loss of sensation and speech, and other problems. A lacunar or small Subcortical stroke affects the inner part of the brain causing small "pea sized" areas of damage due to blockage of small blood vessels within the brain. This multi-center study will recruit 3000 participants (20 percent of whom will be Hispanic) to find out if using aspirin and clopidogrel is more effective than using aspirin alone to prevent recurrent stroke in patients with lacunar stroke confirmed by MRI, and if lowering a patient's blood pressure below the usual limits will also help prevent recurrent stroke and maintain thinking ability. Both aspirin and clopidogrel are widely-used for blood clotting and stroke prevention. Investigators intend to find out if using the drugs together is more effective than using aspirin alone. Participants will be randomly assigned to one of 2 types of treatment: either aspirin alone or the combination of aspirin and clopidogrel. In addition, participants will be assigned to one of 2 groups of blood pressure control. The difference between the two groups is the target level of systolic blood pressure—either 130-149 or below 130. The goal of the blood pressure aspect of this trial is to find out if lowering blood pressure after stroke helps to prevent recurrent stroke and preserves cognition.
INCLUSION: Small subcortical ischemic stroke or subcortical TIA. Inclusion criteria are based on TOAST criteria supplemented by required MRI data. All of the following criteria must be met: - One of the lacunar stroke clinical syndromes (adapted from Fisher) lasting > 24 hrs within the past 6 months - Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc. - No ipsilateral cervical carotid stenosis (≥50%) by a reliable imaging modality done in an approved laboratory since the qualifying small subcortical stroke (S3), if hemispheric. - No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient's primary care physician. - Subcortical TIA with corresponding lesion on DWI. - MRI evidence of S3: a. Presence of an S3 (1.5 and 2 cm in diameter corresponding to the qualifying event on DWI; when TIA, ADC image must confirm lesion or T2/FLAIR (hyperintense lesions) (required for all brainstem events) OR multiple S3s on FLAIR/TI(<1.5 cm in diameter) (hypointense lesions) b. Absence of cortical stroke and large subcortical stroke (recent or remote). EXCLUSION: To be eligible for entry into the study, the patient must not meet any of the criteria listed below: - Disabling stroke (Modified Rankin Scale less than or equal to 4) - Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke - Age under 30 years - High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc) - Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets - Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA - Prior ipsilateral carotid endarterectomy - Impaired renal function: GFR <40 - Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR) - A score < 24 (adjusted for age and education) on the Folstein Mini Mental Status Examination - Medical contraindication to MRI - Pregnancy or women of child-bearing potential who are not following an effective method of contraception - Geographic or social factors making study participation impractical - Unable or unwilling to provide informed consent - Unlikely to be compliant with therapy/unwilling to return for frequent clinic visits - Patients concurrently participating in another study with an investigational drug or device - Other likely specific cause of stroke (e.g. dissection, vasculitis, prothrombotic diathesis, drug abuse)
Minimum Age: 30 Years
Maximum Age: N/A
Healthy Volunteers: No
NCT ID: NCT00715520
Principal Investigator: Cathrin M Buetefisch, MD
Contact: Farrah E Rink, MHSc, 678-369-3152
Enhance motor cortex reorganization with noradrenergic drugs and non-invasive repetitive transcranial magnetic stimulation.
Previous studies have shown, that when patients learn a new motor movement, it may cause a change in the way the nerves act in the area of the brain that controls movement. This change is called use-dependent plasticity. The ability of that part of the brain, called the motor cortex (M1), to reorganize plays a major role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery. In this proposed study we will further examine influences of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of stroke subjects using a combination of non-invasive cortical stimulation, medication, and exercise techniques. In Specific Aim 1, we will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans. In Specific Aim 2, we will identify the parameters for non-invasive TMS stimulation of M1 that are most effective to enhance use-dependent plasticity in intact healthy human M1. Specific Aim 3 will assess the efficacy of plasticity enhancing methods developed in non-injured M1 healthy subjects (Specific Aims 1 & 2) in injured M1 of stroke patients. Our proposal links science to neurorehabilitation practice in stroke patients by applying principles known to enhance practice dependent plasticity in intact human M1 to injured M1 of stroke patients to enhance motor recovery. These newly designed rehabilitation strategies could potentially reduce the morbidity and disability of stroke and, thus, reduce dramatically the costs for long-term ambulatory and nursing home care. The positive impact on the field of neurorehabilitation will be considerable.
For Specific Aims 1 and 2 Inclusion Criteria: - Aged 55 to 80 years - Normal neurological examination - Ability to meet criteria of inclusion experiment - Ability to give informed consent. Exclusion Criteria: - History or neurological or psychiatric disease - Abnormal MRI of brain - Abnormal neuropsychological testing - Intake of CNS active drugs - History of seizure disorder - History of migraine headaches - History of anaphylaxis or allergic reactions - Contraindication to TMS Specific Aim 3: Inclusion Criteria: - Aged 55 to 80 years - Cerebral ischemic infarction more than 12 months prior to entering the study - Single lesion as defined by MRI of the brain affecting the primary motor output system of the hand at a cortical (M1) level - Dense paresis of the hand for more than three days after cerebral infarction - Good functional recovery of hand function as defined by the ability to perform selective movements of the finger at the time of the study - Ability to meet criteria of inclusion experiment - Ability to give informed consent. Exclusion Criteria: - History or neurological or psychiatric disease, including bipolar disorder - Intake of CNS active drugs - History of seizure disorder - History of migraine headaches - History of anaphylaxis or allergic reactions - Contraindication to TMS
Minimum Age: 55 Years
Maximum Age: 80 Years
Healthy Volunteers: Accepts Healthy Volunteers
NCT ID: NCT00576693
Principal Investigator: Marc I Chimowitz, MBChB
PRIMARY HYPOTHESIS: Compared with intensive medical therapy alone, intracranial angioplasty and stenting combined with intensive medical therapy will decrease the risk of the primary endpoint by 35% over a mean follow-up of two years in high-risk patients patients with 70% - 99% intracranial stenosis who had a transient ischemic attack (TIA) or stroke within 30 days prior to enrollment) with symptomatic stenosis of a major intracranial artery. SUMMARY: The best treatment for prevention of another stroke or TIA in patients with narrowing of one of the arteries in the brain is uncertain. A common treatment is the use of anti-clotting medications to prevent blood clots from forming in the narrowed vessel. There are a variety of medicines used for this purpose. These medications are usually taken for the rest of a patient's life. However, a treatment that has been used successfully together with anti-clotting medications in patients with narrowing of the blood vessels of the heart is now being studied in the blood vessels of the brain. This treatment is called stenting. Recent research has also indicated a benefit in prevention of recurring stroke by Intensive Medical Therapy, which is defined as treating risk factors for stroke like high blood pressure, elevated LDL (low density lipids - the "bad" form of cholesterol) and diabetes. The purpose of this study is to compare the safety and effectiveness of either Intensive Medical Therapy PLUS Stenting or Intensive Medical Therapy ONLY in preventing stroke, heart attacks or death. The study will enroll patients over a 5 year period. Each participant will be involved in the study for a minimum of 1 year and a maximum of 3 years. Fifty different medical centers in the United States are part of this study. Both the Clinical Coordinating Center and the Statistical Coordinating Center for the entire study will be located at Emory University.
This will be an investigator initiated and designed Phase III multicenter trial in which patients with TIA or non-disabling stroke within 30 days prior to enrollment that is caused by 70% - 99% stenosis of a major intracranial artery (MCA, carotid, vertebral, or basilar) will be randomized (1:1) at approximately 50 sites to: intensive medical therapy alone (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl) OR intracranial angioplasty and stenting using the Gateway balloon and Wingspan self-expanding nitinol stent (or any future FDA approved iterations of the balloon, stent, or the delivery systems) plus intensive medical therapy (aspirin 325 mg / day for entire follow-up, clopidogrel 75mg per day for 90 days after enrollment unless cardiologist recommends continuing clopidogrel beyond 90 days for a cardiac indication, and aggressive risk factor management primarily targeting blood pressure < 140 / 90 mm Hg (< 130 / 80 if diabetic) and LDL < 70 mg / dl). Risk factor management will be performed by the study neurologist at each site who will be assisted by an innovative, evidence-based, educational, lifestyle modification program (INTERxVENT) that will be administered at regularly scheduled times to all patients throughout the study. All patients enrolled in the trial will be followed until the first of the following: 90 days after a primary endpoint, death, or the close-out visit in the trial, which will occur within a window from 60 days before March 31, 2012 to 30 days after March 31, 2013. Patients who do not die or have a primary endpoint during follow-up will be followed for 2-4.5 years.
INCLUSION CRITERIA 1. Transient ischemic attack (TIA) or non-severe stroke within 30 days of enrollment attributed to 70-99% stenosis of a major intracranial artery (carotid artery, MCA stem (M1), vertebral artery, or basilar artery) • may be diagnosed byTranscranial Doppler (TCD), Magnetic Resonance Angiogram (MRA), or computed tomography angiography (CTA) to qualify for angiogram performed as part of the study protocol but must be confirmed by catheter angiography for enrollment in the trial 2. Modified Rankin score of ≤ 3 3. Target area of stenosis in an intracranial artery that has a normal diameter of 2.00 mm to 4.50 mm 4. Target area of stenosis is less than or equal to 14 mm in length 5. Age ≥ 30 years and ≤ 80 years. • Patients 30-49 years are required to meet at least one additional criteria (i-vi) provided in the table below to qualify for the study. This additional requirement is to increase the likelihood that the symptomatic intracranial stenosis in patients 30-49 years is atherosclerotic. i. insulin dependent diabetes for at least 15 years ii. at least 2 of the following atherosclerotic risk factors: hypertension (BP > 140/90 or on antihypertensive therapy); dyslipidemia (LDL > 130 mg /dl or HDL < 40 mg/dl or fasting triglycerides > 150 mg/dl or on lipid lowering therapy); smoking; non-insulin dependent diabetes or insulin dependent diabetes of less than 15 years duration; family history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, stroke, carotid endarterectomy or stenting, peripheral vascular surgery in parent or sibling who was < 55 years of age for men or < 65 for women at the time of the event ii. history of any of the following: myocardial infarction, coronary artery bypass, coronary angioplasty or stenting, carotid endarterectomy or stenting, or peripheral vascular surgery for atherosclerotic disease iv. any stenosis of an extracranial carotid or vertebral artery, another intracranial artery, subclavian artery, coronary artery, iliac or femoral artery, other lower or upper extremity artery, mesenteric artery, or renal artery that was documented by non-invasive vascular imaging or catheter angiography and is considered atherosclerotic v. aortic arch atheroma documented by non-invasive vascular imaging or catheter angiography vi. any aortic aneurysm documented by non-invasive vascular imaging or catheter angiography that is considered atherosclerotic 6. Negative pregnancy test in a female who has had any menses in the last 18 months 7. Patient is willing and able to return for all follow-up visits required by the protocol 8. Patient is available by phone 9. Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent EXCLUSION CRITERIA 1. Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion (NOTE: an exception is allowed if the occlusion involves a single vertebral artery proximal to a symptomatic basilar artery stenosis and the contralateral vertebral artery is supplying the basilar artery) 2. Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which artery is symptomatic (e.g. if patient has pontine, midbrain, or temporal - occipital symptoms) 3. Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days prior to expected enrollment date 4. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion 5. Plan to perform concomitant angioplasty or stenting of an extracranial vessel tandem to an intracranial stenosis 6. Presence of intraluminal thrombus proximal to or at the target lesion 7. Any aneurysm proximal to or distal to stenotic intracranial artery 8. Intracranial tumor (except meningioma) or any intracranial vascular malformation 9. CT or angiographic evidence of severe calcification at target lesion 10. Thrombolytic therapy within 24 hours prior to enrollment 11. Progressive neurological signs within 24 hours prior to enrollment 12. Brain infarct within previous 30 days of enrollment that is of sufficient size (> 5 cms) to be at risk of hemorrhagic conversion during or after stenting 13. Any hemorrhagic infarct within 14 days prior to enrollment 14. Any hemorrhagic infarct within 15 - 30 days that is associated with mass effect 15. Any history of a primary intracerebral (parenchymal) hemorrhage (ICH) 16. Any other intracranial hemorrhage (subarachnoid, subdural, epidural) within 30 days 17. Any untreated chronic subdural hematoma of greater than 5 mm in thickness 18. Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; any known vasculitic disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; any other intracranial infection; any intracranial stenosis associated with Cerebrospinal fluid (CSF) pleocytosis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; benign angiopathy of central nervous system; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus 19. Presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal atrial fibrillation, mitral stenosis, mechanical valve, endocarditis, intracardiac clot or vegetation, myocardial infarction within three months, dilated cardiomyopathy, left atrial spontaneous echo contrast, ejection fraction less than 30% 20. Known allergy or contraindication to aspirin, clopidogrel, heparin, nitinol, local or general anesthesia 21. History of life-threatening allergy to contrast dye. If not life threatening and can be effectively pretreated, patient can be enrolled at physician's discretion 22. Active peptic ulcer disease, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets < 100,000, hematocrit < 30, International normalized ratio (INR) > 1.5, clotting factor abnormality that increases the risk of bleeding, current alcohol or substance abuse, uncontrolled severe hypertension (systolic pressure > 180 mm Hg or diastolic pressure > 115 mm Hg), severe liver impairment Aspartate Transaminase (AST) or Alanine transaminase (ALT) > 3 x normal, cirrhosis, creatinine > 3.0 (unless on dialysis) 23. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days or planned in the next 90 days after enrollment 24. Indication for warfarin or heparin beyond enrollment (NOTE: exceptions allowed for use of systemic heparin during stenting procedure or subcutaneous heparin for deep vein thrombosis (DVT) prophylaxis while hospitalized) 25. Severe neurological deficit that renders the patient incapable of living independently 26. Dementia or psychiatric problem that prevents the patient from following an outpatient program reliably 27. Co-morbid conditions that may limit survival to less than 3 years 28. Pregnancy or of childbearing potential and unwilling to use contraception for the duration of this study 29. Enrollment in another study that would conflict with the current study
Minimum Age: 30 Years
Maximum Age: 80 Years
Healthy Volunteers: No
NCT ID: NCT01088672
Principal Investigator: Nils Wahlgren, MD
To determine the revascularization rate of the CE-marked Trevo device in large vessel occlusions in ischemic stroke patients. - Revascularization, defined as at least TICI 2a in the vascular territory treated at end of the neuro interventional procedure.
- Clinical outcomes at 90 days - Mortality at 90 days - Device-related serious adverse events (DRSAEs) - Symptomatic ICH rate within 24 (-6/+12) hours post-procedure
Inclusion Criteria: - Age 18-79 (has had 18th birthday, but not yet had 80th birthday) - NIHSS 8 - 30 - Anticipated life expectancy of at least 6 months - No significant pre-stroke disability (mRS less than or equal to 1) - Written informed consent to participate given by patient or legal representative - Angiographic confirmation of a persistent large vessel occlusion, in the internal carotid, middle cerebral M1 and/or M2 segments, basilar or vertebral arteries - Treatable within 8 hours of symptom onset, defined as the first pass being made with the Trevo device. Exclusion Criteria: - Baseline glucose of < 50 mg/dL (2.78 mmol) or > 400 mg / dL (22.20 mmol) - Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR > 3.0 - Treated with Heparin within 48 hours with a PTT greater than 2 times the lab normal - Baseline platelet count < 30,000 - History of severe allergy (more than rash) to contrast medium - Severe, sustained hypertension (SBP > 185 mm Hg or DBP > 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using medication (i.e. Nipride), the patient can be enrolled - Woman of child bearing potential who is known to be pregnant - Patient participating in another clinical study or protocol - For anterior circulation strokes: strokes involving greater than 1/3 of the MCA territory, as determined by hypodensity on the baseline non- contrast CT, or low CBV on CT Perfusion imaging, or restricted diffusion on DWI images - For posterior circulation strokes within the midbrain and/or pons, extensive hypodensity on the baseline CT, or low CBV on CT Perfusion imaging, or extensive restricted diffusion on DWI images - Baseline CT/MR evidence of significant mass effect with midline shift - Baseline CT/MR evidence of hemorrhage - Baseline CT/MR evidence of intracranial tumor (except small meningioma) - Angiographic evidence of vasculitis or arterial dissection - High grade stenosis that cannot be treated safely or which prevents access to the thrombus with the Trevo device - Angiographic evidence of excessive arterial tortuosity that precludes the Trevo device from reaching the thrombus
Minimum Age: 18 Years
Maximum Age: 79 Years
Healthy Volunteers: No