E-Selectin Nasal Instillation to Prevent Secondary Stroke

• Status: Withdrawn
• Trial end date: 2018-05-09
• Target enrollment: 0
• Participant gender: All

Summary

This study will determine the maximum safe dose of the experimental drug E-selectin that can be given to stroke patients. E-selectin causes white blood cells called lymphocytes to change so that they prevent clots from forming in the vessels that supply blood to the brain. The drug has been shown to be effective in animal models of stroke. This study will look at the safety of using this experimental drug in nasal instillation form in patients who have had a stroke or transient ischemic attack (TIA).

Patients 45 years of age or older who have had a recent stroke or TIA (30 to 120 days before entering the study) due to a clot forming in a vessel that supplies blood to the brain may be eligible for this study. They must be taking at least one medication to prevent clots, such as coumadin, aspirin, ticlopidine, or others. Candidates will be screened with a physical and neurological examination, blood and urine tests, electrocardiogram (EKG), echocardiogram (ultrasound test of the heart), and magnetic resonance imaging (MRI) of the brain.

Participants will be randomly assigned to receive E-selectin at a dose level of 5, 15, or 50 micrograms or a placebo (nasal drops with no active ingredient). They will instill a small, carefully premeasured amount (one dose) of fluid in their nose every other day for 10 days (total of 5 doses). This course of treatment will be repeated two times at 3-week intervals. Patients will be followed at 1 month and 3 months with a neurologic examination and blood and urine tests. They will be contacted by phone, fax, or email in between these two visits.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Criteria

• INCLUSION CRITERIA:

1. Occurrence of any type or location of stroke (acute ischemic or primary hemorrhagic stroke) at least 31 days, but not more than 120 days prior to enrollment confirmed by brain imaging (CT or MRI).

2. Age equal to or greater than 45 years.

3. Modified Rankin Score of 0-2 (functionally independent) at the time of study enrollment and determined to be clinically and neurologically stable by the enrolling investigator.

EXCLUSION CRITERIA:

Patients with any of the following conditions will not be eligible for participation in this study:

1. Intracranial or extracranial dissection, Moyamoya disease, vasculitis, radiation-induced vasculopathy, fibromuscular dysplasia, venous thrombosis.

2. Current treatment with Immunosuppressive medication including: prednisone, cyclophosphamide, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, anti-CD3 moab (Othoclone OKT3), takrolimus (FK506), sirolimus, anti-IL2r moab (simulect, zenapax), etanercept, infliximab, lenercept, thymoglobulin; thalidomide.

3. Known active autoimmune diseases (RA, LE, MS, Myasthenia Gravis, etc.).

4. Active cancer or lymphoproliferative diseases. (except for basal cell carcinoma)

5. Thrombocytopenia (platelets less than 100,000).

6. HIV or other known immunodeficiencies.

7. Recent major surgery performed within one month of study enrollment.

8. Active systemic infections, or severe focal or upper respiratory infections (URI).

9. Alcohol or substance abuse.

10. Dementia or psychiatric problems (determined by examination, mini-mental status test) that prevents the patient from providing informed consent or following an outpatient program reliably.

11. Pregnancy (urine pregnancy test will be given to women of childbearing potential).

12. Severe rhinopathy or sinusitis.

13. Continuing use of any other over the counter, prescribed or recreational intranasal drug.

14. History of NCI grade 3 epistaxis within 1 month.

15. Exposure to an investigational drug within the 30 days prior to screening for this study.

16. Planned surgery (e.g. carotid or cardiac surgery) or endovascular intervention during the study period until study variables have returned to baseline to prevent attributions of surgical complications to E-selectin tolerization.

17. Patients who are not eligible for or unable to tolerate a brain MRI prior to the start of study drug.