Active Clinical Trials for patients
with Cerebrovascular Disease

• CLOSURE I Clinical Trial
• Carotid Occlusion Surgery Study NS 42167
• FAST Clinical Trial
• IRIS Trial
• PRoFESS Clinical Trial
• SWISS Trial (Siblings With Ischemic Stroke Study)

CLOSURE I Clinical Trial
Title: A prospective, multicenter, randomized controlled trial to evaluate the safety and efficacy of the Starflex Septal Closure system versus best medical therapy in patients with a stroke and/or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale. (CLOSURE I Study)
Sponsor: Private Industry
Investigator: Harold P. Adams, Jr., email harold-adams@uiowa.edu

Coordinator: Jeri Sieren, RN, email jeri-sieren@uiowa.edu
Description: This is a prospective, multi-center, randomized two-arm study enrolling 1600 patients who have had an index embolic stroke and/or transient ischemic attack (TIA) in the previous 3 months with evidence of a patent foramen ovale (PFO) and in whom there is no other identifiable etiology (e.g. cryptogenic stroke patient). The PFO must be amenable to percutaneous closure with the STARFlex device. In placement of permanent intracardiac devices may be performed during the index procedure. Clinical follow-up for all patients will be performed at 1 (phone call), 6,12, and 24 months post-enrollment.
Inclusions/Exclusions: See below
Status: Currently recruiting patients.

Contact: If you have a patient who may be eligible for this study, please call 319-356-4110 or 319- 356-1616 and ask for Pager 3547 (Stroke Study Pager).
Inclusions:

Prior to randomization

1. The patient is > 18 years of age and < 60 years of age
2. Patients must have a positive contrast valsalva bubble study by TEE, demonstrating right to left shunting through a PFO during valsalva (see Appendix D for procedure and bubble study grade categories). An atrial septal aneurysm may or may not be identified.
3. Patients must be available for follow-up in accordance with the protocol.
4. Patients must be able to provide informed consent, or, if unable, a legal guardian must provide informed consent.
5. The vascular access from the femoral vein is expected to accommodate the 10F delivery system.
6. Critical cardiac structures are not expected to come in contact with the device (e.g., AV valves and pulmonary veins). (It is recommended that the device be approximately 1 mm from the structure).
7. The risks and benefits of both treatments have been fully explained to the patient by the neurologist.
8. Patients must have discontinued use of hormonal contraceptives before enrollment into the study and agree to avoid future use during the entire study period. (HRT use is allowed if not being used for contraception purposes.)
9. Stroke or definite clinical TIA within 3 months without other identifiable cause.
10. A patient presenting with definite clinical TIA meeting the following criteria: patient experiences a sudden focal neurological event lasting at least 10 minutes without evidence of acute ischemic brain injury on DW-MR imaging, with symptoms consisting of hemiplegia/paresis, monoplegia/paresis, quadraplegia/paresis, language disturbance other than isolated slurred speech, blindness in one or both eyes, or significant difficulty walking. Dysarthria, vertigo, sensory symptoms, confusion, memory loss, syncope, lightheadedness or diplopia will not be accepted in isolation. Such symptoms must be accompanied by focal weakness or combinations of multiple symptoms localizable to the anterior or posterior circulation to be accepted as TIAs. Atypical symptoms such as a marching evolution, positive phenomena such as visual scintillations, or prominent unilateral throbbing headache suggesting migraine will be characterized as "transient neurological events of unknown etiology" and will NOT be called TIAs.

Post-randomization – device patients only

11. The size of the PFO (measured by indentation with a soft balloon) must be amenable to selection of a STARFlex device as described in the Instructions For Use. (Refer to Appendix A).

Exclusions:

1. A contrast valsalva bubble study demonstrating no shunting from right to left through a PFO (see Appendix D for bubble study grade categories.
2. There is a potential source of embolic stroke or TIA other than PFO, including but not limited to:
   1. Carotid artery stenosis >50% (or less if stenosis is ulcerated or associated with thrombus);
   2. >50% intracranial stenosis appropriate to patient’s symptoms;
   3. Complex aortic arch atheroma exhibiting high-risk features for embolism;
   4. Aortic arch, carotid artery, or vertebral artery dissection;
   5. Severe mitral valve stenosis;
   6. Severe aortic stenosis;
   7. Mitral or aortic valve vegetations;
   8. Mitral or aortic valve calcified annulus, classified as > 5mm MAC thickness;
   9. Prosthetic heart valves in any location;
   10. Left ventricular ejection fraction of < 30% by echocardiography or ventriculography;
   11. Left ventricular aneurysm;
   12. Recent anterior wall myocardial infarction within the three month period preceding the neurological event;
   13. Chronic atrial fibrillation, paroxysmal atrial fibrillation, or flutter defined as a history of > 2 documented episodes lasting more than 30 seconds each and unrelated to a reversible cause (such as acute myocardial infarction, cardiac surgery, myocarditis, hyperthyroidism, or acute pulmonary disease). Patients meeting this definition will be excluded regardless of persistent or paroxysmal nature of the arrhythmia. (ACC/AHA guideline of AF terminology).
3. Based on echocardiographic assessment, a large, redundant atrial septal aneurysm which cannot, in the judgment of the investigator, be covered by the STARFlex device without (1) causing the device to interfere with other intracardiac structures, or (2) prohibiting the ability of the operator to adequately deploy the distal/proximal arms in the left/right atrium prior to final placement on the septum.
4. Congenital cardiac defects not repaired prior to enrollment, including:
   1. Atrial septal defect;
   2. Ventricular septal defect;
   3. Coarctation of the aorta; or
   4. Patent ductus arteriosus.
5. Thrombus in or occlusion of the venous lumen between the femoral vein access site (or superior access site, if used) and the right atrium.
6. A previously implanted atrial septal device.
7. Echocardiographic evidence of an intra - atrial or ventricular thrombus.
8. History of recent (within the past 6 months) or current intravenous drug abuse.
9. Known active endocarditis or documented bacteremia.
10. Serum creatinine > 2.0 mg/dL.
11. Active infections requiring current antibiotic therapy (if temporary illness, patients may enroll after discontinuation of antibiotics, once asymptomatic for 4 weeks.)
12. Women with suspected or known pregnancy.
13. Known hypersensitivity or contraindication (i.e., TPA administration or any endovascular intervention for acute stroke within 7 days) to warfarin treatment.
14. A known contraindication to aspirin, heparin, clopidogrel or a sensitivity to contrast media, which cannot be adequately pre-medicated.
15. Any medical condition (other than index stroke) requiring anticoagulation with warfarin.
16. A platelet count <100,000 cells/mm³ or >700,000 cells/mm³, or a WBC of <3,000 cells/mm³, or a disorder of platelet function such as thrombocytosis.
17. Any patient with a coagulopathy (i.e. prothrombin G20210A, protein C, protein S, anti-thrombin III deficiency, factor V leiden deficiency). These tests must be performed before randomization.
18. Patients with a moderate or high positive titer, as defined per study site, of antiphospholipid antibodies. Testing for antiphospholipid antibodies to include, at a minimum, lupus anticoagulant and anticardiolipin antibodies. These tests must be performed before randomization.
19. Patients with known vasculitis or neurologic disorder including systemic lupus erythematosis, giant cell arteritis, or multiple sclerosis,
20. Patients unable to perform a satisfactory valsalva maneuver.
21. Patients in whom transesophageal echocardiography is contraindicated.
22. Active peptic ulcer or upper GI bleeding within the prior 6 months.
23. Concurrent medical condition with a life expectancy of less than 24 months.
24. Currently participating in an investigational drug or another device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints. [Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.]
25. The presence of a permanent pacemaker.
26. The presence of an inferior vena cava filter.
27. Normal RV function and PVR > 10 indexed Wood units if RV pressure < 1/2 systemic pressure or, PVR > 8 indexed Wood units if RV pressure > 1/2 systemic pressure.
28. If echocardiography suggests moderate or greater tricuspid regurgitation
29. Suspected/recognized cirrhosis or portal hypertension or known pulmonary AVM’s
30. Baseline Modified Rankin Score of 3 or more

Carotid Occlusion Surgery Study NS 42167
Description: This randomized, non-blinded, prospective multi-center study is to determine if surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to best medical therapy can reduce by 40%, despite perioperative stroke and death, subsequent ipsilateral ischemic stroke (fatal and non-fatal) at two years in subjects with recently (< 120 days) symptomatic internal carotid artery occlusion and ipsilateral increased oxygen extraction fraction measured by positron emission tomography (PET).

Inclusions/Exclusions: See below

Sponsor: NIH

Investigators: Drs. Patrick Hitchon and Patricia Davis

Coordinators: Pam Jacobs or Melanie Frees

Phone: (319) 384-8288 or (319) 384-5824
E-mail: pamela-jacobs@uiowa.edu or melanie-frees@uiowa.edu
Status: Currently recruiting patients

Inclusion Criteria

All must be answered "YES".

• Vascular imaging demonstrating occlusion an internal carotid artery

  NOTE: The above inclusion criteria may be demonstrated by any vascular imaging modality (e.g. Doppler ultrasound, magnetic resonance angiography, CT angiography or intra-arterial catheter arteriography). Validation of sensitivity and specificity of non-arteriographic modalities versus arteriography is not required since all participants must have catheter arteriography to determine final eligibility.

• Transient ischemic attack (TIA) or ischemic stroke in the hemispheric carotid territory of the occluded carotid artery
  • This is a clinical diagnosis based on all available data that does not require confirmation by neuroimaging. Participants with TIA or infarction restricted to the retina only are not eligible, but those with combined retinal and hemispheric carotid territory syndromes will be eligible. In participants with hemisensory or hemimotor signs or symptoms, including single limb, specific hemispheric signs or symptoms (e.g. aphasia) will not be required for inclusion but absence of cerebellar and brainstem signs or symptoms will be required.
  • Participants who have previously undergone endarterectomy for stenosis of the ipsilateral external carotid or contralateral internal carotid artery are eligible whether or not they have had recurrent symptoms.
  • Participants who have undergone carotid endarderectomy (CEA) for symptomatic carotid stenosis who develop a post-operative carotid occlusion but experience no further symptoms after the time of surgery are not eligible unless further symptoms occur.
• Most recent qualifying TIA or stroke occurring within 120 days prior to performance date of PET
• Modified Barthel Index >12/20
• Language comprehension intact, motor aphasia mild or absent such that effective communication with the participant is possible
• Age 18-85 years inclusive
• Competent to give informed consent
• Legally an adult
• Geographically accessible and reliable for follow-up

Exclusion Criteria

All must be answered "NO".

• Non-atherosclerotic carotid vascular disease

  The intent is to include only atherosclerotic carotid occlusion. All other non-atherosclerotic conditions (for example, moya-moya disease, fibromuscular dysplasia, carotid dissection, arteritis, radiation-induced vasculopathy such as that following irradiation for neck cancer) are excluded. These entities are given as examples, not as an all-inclusive list.

• Blood dyscrasias
  This includes the following conditions ONLY:
  • Polycythemia vera
  • Essential thrombocytosis
  • Sickle cell disease (SS or SC)

  This is an all-inclusive list. The following conditions are NOT EXCLUSIONS: anticardiolipin antibodies, lupus anticoagulant, protein S, C, or antithrombin III deficiency, Factor V Leiden or other causes of activated protein C resistance, prothrombin gene mutations.

• Known heart disease likely to cause cerebral ischemia (Echocardiography is not required.)
  This includes the following conditions ONLY:
  • Prosthetic Valves
  • Infective endocarditis
  • Left atrial or ventricular thrombus
  • Sick sinus syndrome
  • Myxoma
  • Cardiomyopathy with ejection fraction < 25%

  This is an all-inclusive list. The following conditions are NOT EXCLUSIONS: atrial fibrillation, patent foramen ovale, atrial septal aneurysm.

• Other non-atherosclerotic condition likely to cause focal cerebral ischemia
• Any condition likely to lead to death within 2 years
• Other neurological disease that would confound follow-up assessment
• Pregnancy
• Subsequent cerebrovascular surgery planned which might alter cerebral hemodynamics or stroke risk

  This includes contralateral internal or common carotid endarterectomy or angiopalsty, ipsilateral external carotid artery endarterectomy or angioplasty, carotid stump closure, vertebral or basilar artery angioplasty, any arterial grafting procedures to the carotid or vertebral arteries.

• Any condition which in the participating surgeon’s judgment makes the participant an unsuitable surgical candidate
• Concurrent participation in any other experimental treatment trial
• Participation within the previous 12 months in any experimental study that included exposure to ionizing radiation
• Acute, progressing or unstable neurological deficit (Neurological deficit must stable for 72 hours prior to the performance of PET).

  If supplemental arteriography is required, allergy to iodine or X-ray contrast media, serum creatinine > 3.0 mg/dl or other contraindication to arteriography

• Allergy or contraindication to aspirin
• Medical indication for treatment with anticoagulant drugs, ticlopidine, clopidogrel or other antithrombotic medications such that these medications cannot be replaced with aspirin in the perioperative period as deemed necessary by the COSS neurosurgeon if the participant is randomized to surgical treatment.

  NOTE: Participants with any of the medical conditions specified in exclusion criteria 17 through 20 can become eligible if the exclusion criterion no longer applies within 120 days of onset of the most recent qualifying event.

• Uncontrolled diabetes mellitus (FBS > 300 mg%/16.7 mmol/L)
• Uncontrolled hypertension (systolic BP>180, diastolic BP >110)
• Uncontrolled hypotension (diastolic BP <65)
• Unstable angina

FAST Clinical Trial

Title: Randomized, Double-Blind, Placebo Controlled, Multi-Center, Parallel Groups Confirmatory Efficacy and Safety Trial of Activated Recombinant Factor VII (NovoSeven®) in Acute Intracerebral Hemorrhage

Sponsor: Private Industry

Investigator: Patricia Davis, MD, email pat-davis@uiowa.edu

Coordinator: Karla Grimsman, RN, email karla-grimsman@uiowa.edu

Description: To evaluate the efficacy and safety of recombinant activated factor FVII (rFVIIa/NovoSeven®) in reducing disability and improving clinical outcome by preventing early hematoma growth in patients with acute intracerebral hemorrhage (ICH). The trial is a randomized, double-blind, multi-center, multi-national, placebo-controlled efficacy and safety trial with three treatment arms: 20 µ/kg or 80 µ/kg rFVIIa or placebo.

Inclusions/Exclusions: See Below

Status: Currently recruiting patients

Contact: If you have a patient who may be eligible for this study, please call 319- 356-1616 and ask for Pager 3547 (Stroke Study Pager).

Inclusion Criteria:

• Spontaneous ICH (including bleeding in brainstem and cerebellum) diagnosed by a computerized tomography (CT) scan within 3 hours of symptom onset
• Male or female patients, aged >18 years
• Informed consent obtained before any trial related activities.

Exclusion Criteria

• Time of symptom onset of ICH is unknown or more than 3 hours
• Patients with secondary ICH related to infarction, tumor, hemorrhagic infarction, cerebrovenous thrombosis, aneurysm, arteriovenous malformations (AVM), thrombolysis or severe trauma
• Surgical hematoma evacuation planned within 24 hours of symptom onset
• Deep coma (Glasgow Coma Score (GCS) 3-5) at the time of admission
• Known oral anti-coagulant use (unless the international normalized ratio (INR) is documented
• below 1.4); aspirin use is not an exclusion criterion
• Known thrombocytopenia (unless current platelets documented above 50000/µL)
• Pre-existing disability (i.e. must have a mRS score of 0-2 before stroke)
• Any known history of hemophilia or other coagulopathy
• Known acute myocardial ischemia, unresolved unstable angina, acute septicemia, acute crush injury, acute disseminated intravascular coagulation (DIC) or acute thrombotic stroke
• Pregnancy
• Known or suspected allergy to trial product or related products
• Previous participation in this trial
• Known participation in ANY investigational drug or device trial within 30 days of entry into this trial
• Patients known or suspected of not being able to comply with this trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder)

IRIS Trial

Title: Insulin Resistance Intervention after Stroke

Sponsor: National Institutes of Health

Investigator: Enrique Leira, email enrique-leira@uiowa.edu

Coordinator: Jeri Sieren, RN, email jeri-sieren@uiowa.edu

Description: A randomized, placebo-controlled trial of pioglitazone (an insulin sensitizer) for prevention of recurrent stroke and myocardial infarction in patients with a recent ischemic stroke.

Inclusions/Exclusions: See below
Status: Currently recruiting patients.

Contact: If you have a patient who may be eligible for this study, please call 319-356-4110 or 319- 356-1616 and ask for Pager 3547 (Stroke Study Pager).

Inclusion Criteria:

• Non-diabetic men and women
• Age 45+ years
• Ischemic stroke within prior 6 months
• Able to give informed consent
• Insulin resistant (IRIS blood test)

Exclusion Criteria:

• Stroke due to cardioembolism (unless lacunar infarct or carotid stenosis is also present), dissection, trauma, or instrumentation
• Severely disabled by stroke
• Class III or IV heart failure
• Chronic liver disease
• Limited life-expectancy 2° comorbidity
• Use of oral steroids or contraceptives
• Pregnancy or intended pregnancy

PRoFESS Clinical Trial

Title: PRoFESS — Prevention Regimen For Effectively avoiding Second Strokes: A double-blind, active and placebo controlled study of Aggrenox® vs. clopidogrel, with and without Micardis®

Sponsor: Private Industry

Investigator: Patricia Davis, MD, email pat-davis@uiowa.edu

Coordinator: Jeri Sieren, RN, email jeri-sieren@uiowa.edu

Description: Multi-national, double-blind, double-dummy, active and placebo controlled, parallel group, 2 X 2 factorial design. The randomization is stratified by baseline usage of an ACE-inhibitor. Enrollment period is projected to be 2 years; total study duration is projected to be 4 years, based on the estimated time until 2280 strokes occur among randomized patients.

Inclusions/Exclusions: See Below

Status: Currently recruiting patients

Inclusions:

1. Patients who are at least 50 years of age and who have had an ischemic stroke within 120 days of entry into the study. Stroke is defined as a new focal neurologic deficit of vascular origin lasting more than 24 hours, or where there is evidence of a new brain infarct upon brain imaging. The diagnosis of the ischemic stroke is based upon the clinical judgment of the investigator supplemented with evidence on a computerized tomography (CT) scan or other imaging modality, e.g., magnetic resonance imaging (MRI) of the brain. Patients must have 2 additional risk factors to be enrolled if age 50-54 and/or 90-120 days after qualifying stroke (diabetes mellitus; hypertension, systolic BP > 140 or diastolic BP > 90; obesity BMI > 30; previous vascular disease, stroke, MI, or peripheral arterial disease prior to qualifying stroke.)
   1. For patients whose symptoms last more than 24 hours, the following is required:
      1. Brain imaging which excludes hemorrhagic stroke.

         (Note that it is NOT required that brain imaging confirm the presence of an ischemic brain infarct. Clinical symptomatology that a stroke has occurred is sufficient.)

   2. For patients whose symptoms last less than 24 hours, the following is required:
      1. Brain imaging which excludes hemorrhagic stroke.
      2. Brain imaging which confirms the presence of a new brain infarct consistent with the clinical syndrome.
2. The patient’s neurological and clinical condition following the qualifying stroke must have stabilized in the opinion of the investigator, i.e., the patient is not deteriorating or evidencing a progressive stroke or other condition. Treatment with study medication should begin as soon as possible following the qualifying stroke, as soon as the patient is neurologically and clinically stable, and taking into account all inclusion and exclusion criteria. For hospitalized patients the requirement of clinical stability includes the requirement that blood pressures be stable, as evidenced by multiple measurements over the previous 24 hours demonstrating that blood pressures have remained within the acceptable range for randomization (lower than 180/110 mmHg, but systolic BP is higher than 120 mmHg). Patients who are not randomized because of unstable or unacceptable blood pressures, or who are not neurologically and clinically stable may be randomized at a later time if their condition improves, and they then still meet all the requirements for randomization.

Exclusions:

1. Patients unable to give informed consent.
2. Patients presenting with a primary hemorrhagic stroke (intracerebral hemorrhage or subarachnoid hemorrhage) are excluded. Hemorrhagic stroke must be excluded by means of appropriate brain imaging (e.g., CT scan, MRI). Note that patients with infarction with secondary hemorrhagic components at the time of presentation will be eligible if in the Investigator’s opinion the risk of further hemorrhage has diminished by the time of randomization.
3. Patients who are unable to take by mouth all required study medication. (Crushing tablets, taking capsules apart, or in any way altering the study medication is not allowed.)
4. Known brain tumor.
5. Current congestive heart failure, defined as a previous definitive diagnosis, or present symptoms of at least Category II of the NYHA classification system for CHF
6. Patients with a pre-stroke history of dementia requiring institutional care.
7. A Modified Rankin Scale score >4 at baseline.
8. The patient is unlikely to be released from hospital following the qualifying stroke, or the presence of a severe disability after the qualifying stroke likely to lead to the patient being bedridden or demented, or a non-vascular disease or condition which makes it unlikely that the patient will survive to the end of the trial.
9. Patients whose qualifying stroke had been induced by a surgical or cardiovascular procedure such as carotid endarterectomy, angiogram, or cardiac surgery.
10. Patients with known hypersensitivity to dipyridamole, clopidogrel, aspirin, or telmisartan (Micardis®).
11. Uncontrolled hypertension which equals or exceeds either a sitting systolic blood pressure greater than 180 mmHg, or a sitting diastolic blood pressure greater than 110mmHg will exclude the patient.
12. Seated systolic blood pressure <120 mmHg for patients who are still hospitalized following the qualifying stroke. (If patient can not sit, supine blood pressure is acceptable.)
13. Patients currently being treated with an ARB (angiotensin II receptor blocker) who are unable or unwilling to discontinue treatment with this type of drug. (For patients who require treatment for hypertension, the following classes of agents are suggested: diuretics; beta blockers; calcium channel blockers; central alpha agonists such as clonidine.)
14. Patients with required or planned continued treatment with antithrombotics or anticoagulants including heparin or warfarin, or non-study platelet inhibitors, or non-steroidal anti-inflammatory drugs unless they are selective COX-2 inhibitors (e.g. celecoxib). Note that the short-term use (usually a few days) of low dose unfractionated heparin, low-molecular weight heparin, or heparinoids for prophylaxis of development of deep venous thrombosis during the acute post-stroke period is allowed, i.e., may be administered along with study medication.
15. Known severe renal insufficiency defined as renal artery stenosis, or creatinine clearance <0.6 ml/sec or serum creatinine >3.0 mg/dL.
16. Known severe hepatic dysfunction as defined by the following laboratory parameters: SGPT (ALT) or SGOT (AST) >4 times upper limit of normal, or total bilirubin >20micromol/L.
17. Hyperkalemia, defined as potassium >5.5 mmol/L
18. Uncorrected volume depletion or sodium depletion. Patients must be properly hydrated.
19. Known current active peptic ulcer disease.
20. Patients with the syndrome of asthma, rhinitis and nasal polyps (all three present).
21. Known severe coronary artery disease including unstable angina pectoris or a myocardial infarction within the previous 3 months.
22. Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration.
23. Known presence of or history of a hemostatic disorder or systemic bleeding.
24. History of thrombocytopenia (i.e., less than 100x109 /L for platelets) or neutropenia (1.2x109 /L for neutrophils).
25. Women who are breast feeding, pregnant, or of childbearing potential who do not use a medically acceptable form of contraception (surgical sterilization, birth control pills, an implantable contraceptive device, birth control injections, or an IUD). Barrier methods such as condoms and diaphragms are not acceptable. NOTE: While most women in this study will not be of childbearing potential, for any woman who is, a negative pregnancy test, urine or serum, must be obtained prior to entry into the study.
26. Patients who have been exposed to an investigational drug or device within the last 30 days, or currently participating in such a trial, are excluded.
27. Patients scheduled for major surgery, carotid endarterectomy, or carotid angioplasty should not enter the study. Such patients may enter the trial 4 weeks after such procedures, if it has not been more than 90 days since the qualifying (most recent) stroke, and they meet all other entrance requirements.

SWISS Trial (Siblings With Ischemic Stroke Study)
Sponsor: National Institutes of Health
Local Investigator: Patricia Davis, email pat-davis@uiowa.edu
Coordinators: Jeri Sieren, RN, email jeri-sieren@uiowa.edu

Description: A multi-center study of sibling pairs with stroke to systematically screen for regions of the human genome that contain genes which increase the risk of having an ischemic stroke using DNA samples collected in this study from 300 affected sibling pairs. A genome-wide screen using microsatellite markers spaced at 20 centimorgan intervals will be performed. An anonymous cell bank of specimens from these sibling pairs and an accompanying database of genetic and phenotypic data will be established. The study involves one research visit and one blood test.
Status: Currently recruiting patients

Contact: If you have a patient who may be eligible for this study, please call 319-356-4110 or 319- 356-1616 and ask for Pager 3547 (Stroke Study Pager).

Proband Inclusions:

1. A confirmed diagnosis of Ischemic stroke (defined as having had computed tomographic or MRI of the brain within 7 days of on set of symptoms which fails to identify an etiology other than cerebral infarction).
2. At least one living full sibling with a history of stroke.
3. 18 years or older at the time of enrollment.

Proband Exclusions:

1. Index ischemic stroke occurred within 48 hours after a cardiovascular or cerebrovascular procedure.
2. Index stroke occurred within 60 days after a non-traumatic subarachnoid hemorrhage.
3. History of brain-biopsy-proven CNS vasculitis at any time prior to enrollment.
4. Known to have any of the following: CADASIL, Fabry's Disease, Homocysteinuria, MELAS, or Sickle Cell Anemia.
5. Mechanical aortic or mitral valve at the time of index stroke onset.
6. Untreated or actively treated bacterial endocarditis at the time of index stroke onset.

A patient or patient's non-investigator surrogate will invite other family members to participate.

Concordant Sibling Inclusions:

1. A full sibling enrolled as a proband in SWISS.
2. Stroke Verification Committee has diagnosed an ischemic stroke.
3. Age 18 or older at the time of enrollment.

Concordant Sibling Exclusions:

1. Index ischemic stroke occurred within 48 hours after a cardiovascular or cerebrovascular procedure.
2. Index ischemic stroke occurred within 60 days after a non-traumatic subarachnoid hemorrhage.
3. History of brain-biopsy-proven CNS vasculitis at any time prior to enrollment.
4. Known to have any of the following: CADASIL, Fabry's Disease, Homocysteinuria, MELAS, or Sickle Cell Anemia.
5. Mechanical aortic or mitral valve at the time of index stroke onset.
6. Untreated or actively treated bacterial endocarditis at the time of index stroke onset.

Discordant Sibling Inclusions:

1. Subject has 2 or more full siblings who are concordant for ischemic stroke by SWISS criteria.
2. Answers negatively to all items on the questionnaire for Verifying Stroke-Free Status.
3. 18 years or older at the time of enrollment.

Discordant Sibling Exclusion:

1. Subject is an unreliable historian in the opinion of interviewer administering the questionnaire for Verifying Stroke-free Status.