E-Selectin Nasal Spray to Prevent Stroke Recurrence

Terminated

Phase 2 Results N/A

Trial Description

This study will test the safety and effectiveness of a protein called E-selectin, given as a nasal spray, in preventing the formation of blood clots that can cause stroke. In animal studies, animals that received E-selectin in the nose on a regular schedule had almost no strokes compared with those that did not receive it.
Patients over age 45 who have had a stroke or transient ischemic attack (TIA) within 1 to 4 months of this study may be eligible to participate. Candidates will be screened with a review of their past medical records and neurologic and medical evaluations that may include magnetic resonance imaging (MRI) of the brain, ultrasound or magnetic resonance angiography (a type of MRI) of the carotid arteries (arteries in the neck that supply blood to the brain), echocardiography (ultrasound test of the heart), electrocardiography (EKG) and blood tests.
Participants will have a blood and urine test and will be assigned to one of four treatment groups. Patients in each group will spray a small amount of fluid into their nose according to the following schedule: 5 doses once every other day for 10-days, followed in 3 weeks by another 5 doses every other day for 10-days, followed in 3 weeks by a final series of 5 doses every other day for 10 days. The spray for patients in each group contains the following:
- Group 1 - fluid with low dose of E-selectin
- Group 2 - fluid with medium dose of E-selectin
- Group 3 - fluid with high dose of E-selectin
- Group 4 - fluid with no E-selectin
Patients will be seen for follow-up visits at 1 month and 3 months after starting E-selectin therapy. The visits will include a neurologic examination and blood and urine tests. Patients will be contacted by phone, fax or e-mail in between the 1- and 3-month visits.

Detailed Description

In the United States, stroke is the third leading cause of death and the leading cause of disability. Despite the success of recent clinical trials of antithrombotic drugs for the secondary prevention of stroke, annually about 10% of patients with recent cerebrovascular accidents have recurrent strokes. The development of new treatment strategies for the secondary prevention of stroke is an important issue for modern medicine. There is increasing evidence that inflammation at the sites of endothelial activation plays an important role in the pathogenesis of stroke. Control of molecular inflammation at the sites of endothelial activation can be achieved by induction of mucosal tolerance. The induction of mucosal tolerance with repeated, low-dose, intranasal administration of antigen causes a shift of immune response from proinflammatory T(H)1 type to anti-inflammatory T(H)2 type at the sites of inflammation. E-selectin is an adhesion molecule expressed only on activated endothelium in response to proinflammatory cytokines. The major goal of proposed study is to test whether repeated administration of low-dose, intranasal E-selectin can induce mucosal tolerance to this compound causing a shift of immune response from T(H)1 to T(H)2 type in patients with recent stroke or TIA, and secondly to evaluate the safety and tolerability of this strategy for the secondary prevention of stroke.

Conditions

Interventions

  • E-selectin Drug
    Intervention Desc: E-selectin is a cell surface receptor that is expressed by endothelial cells and mediates the binding of various white blood cells (leukocytes), including neutrophils, monocytes and some types of memory T cells, to the endothelial cells. Leukocyte adhesion to endothelial cells is a critical step in the migration of a leukocyte out of a blood vessel and into a tissue. Leukocytes are an important component of inflammatory and immunological responses.
  • E-Selectin nasal spray Drug

Trial Design

  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study

Patient Involvement

Participants will have a blood and urine test and will be assigned to one of four treatment groups. Patients in each group will spray a small amount of fluid into their nose according to the following schedule: 5 doses once every other day for 10-days, followed in 3 weeks by another 5 doses every other day for 10-days, followed in 3 weeks by a final series of 5 doses every other day for 10 days. The spray for patients in each group contains the following:

Group 1 - fluid with low dose of E-selectin Group 2 - fluid with medium dose of E-selectin Group 3 - fluid with high dose of E-selectin Group 4 - fluid with no E-selectin Patients will be seen for follow-up visits at 1 month and 3 months after starting E-selectin therapy. The visits will include a neurologic examination and blood and urine tests. Patients will be contacted by phone, fax or e-mail in between the 1- and 3-month visits.

Outcomes

Type Measure Time Frame Safety Issue
Primary To test whether repeated administration of low-dose E-selectin can induce mucosal tolerance causing a shift of immune response from proinflammatory to anti-inflammatory.

Sponsors