Stroke Trials Registry

Induction of mucosal tolerance to E-selectin for the secondary prevention of stroke

Contact Address
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754

Contact Email
prpl@mail.cc.nih.gov

Sponsor

Trial Phase:	Phase II
Study Size Planned:	60
Centers Planned:	1
Max Time from onset:	4 Months
Min Age:	45
Follow-up Duration:	3 Months
ISRCTN#	NCT00012454

Status:
This trial is completed.

Purpose:
To test the safety and efficacy of E-selectin, administered as a nasal spray, in preventing the formation of blood clots that can cause stroke

Interventions:

E-selectin
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.

Location(s):
Maryland

Year Started: 2001

Year Finished: 2004

Design:
Interventional, Treatment, Safety/Efficacy Study

Inclusion Criteria
Patients on at least one antithrombotic medication and on cholesterol-lowering, antihypertensive, antidiabetic, and non-steroidal anti-flammatory medication. Patients treated with t-PA in an acute phase of stroke are also eligible.

Exclusion Criteria
Patients with intracranial or extracranial dissection, Moya Moya disease, vasculitis, radiation-induced vasculopathy, fibromuscular displasia, venous thrombosis. Patients taking immunosuppressive medication, have known autoimmune diseases, cancer and lymp

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.

Primary Outcome:
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.

Comments:
Correspondence to John M. Hallenbeck, MD, Stroke Branch, NINDS, NIH, Bldg 36, Room 4A03, 36 Convent Dr, MSC 4128, Bethesda, MD 20892-4128. E-mail Hallenbj@ninds.nih.gov

Source of Information:
ClinicalTrials.gov

Web Links and Publications:

E-Selectin Nasal Spray to Prevent Stroke Recurrence
ClinicalTrials.gov

Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis.
Brain Res 2007 Feb 9;1132(1):177-84

Induction of mucosal tolerance to E-selectin targets immunomodulation to activating vessel segments and prevents ischemic and hemorrhagic stroke.
Ernst Schering Res Found Workshop 2004;(47):117-32

Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury.
Proc Natl Acad Sci U S A 2003 Dec 9;100(25):15107-12

This information last updated on: 4/30/2010

Reviewed on: 05/19/2009.

UID: 536