Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00069069
Status:
WITHDRAWN
Last Update Posted:
2018-07-05
First Post:
2006-07-12
Brief Title:
E-Selectin Nasal Instillation to Prevent Secondary Stroke
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Induction of Mucosal Tolerance to Human E-Selectin for the Secondary Prevention of Stroke
Status:
WITHDRAWN
Status Verified Date:
2018-05-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
In the United States stroke is the third leading cause of death and the leading cause of disability Despite the use of antithrombotic drugs for the secondary prevention of stroke 10 of patients who experience a cerebral ischemic event will go on to have a stroke within 90 days Claiborne Johnston et al 2003 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 proinflamatory T helper type 1TH1 effects to anti-inflammatory immunmomodulatory regulatory T cell Treg or T helper type 2 TH2 effects at the sites of inflammation E-selectin is an adhesion molecule expressed only on activated endothelium in response to proinflammatory cytokines
Objective The goals of the study are a to test whether repeated administration of low-dose intranasal E-selectin is safe and tolerable and b to test whether it can induce mucosal tolerance to this compound causing a shift of immune response from TH1 to TH2 type with production of Treg cells
Study Population The study population will include 3-50 patients depending on dose escalation events plus 0-8 replacement patients depending on the number of drop outs with recent 30 and 120 days occurrence of any type or location of stroke documented by CT or MRI The final number of patients will be determined by a dose escalation plan described below that may stop early in the accrual process should adverse events arise Since patients will be required to make serial visits to the NIH clinical center a functional recovery score of 0-2 on the modified Rankin Scale ie 0 no symptoms at all 2 slight disability unable to carry out all previous activities but able to look after own affairs without assistance is required for inclusion in this study
Study Design This is a single center Phase 1 open label dose escalation trial assessing safety profile of four doses of intranasal recombinant human E-selectin
Outcome Measures The primary goal of this study is to define the maximum tolerated dose of intranasal instillation of recombinant human E-selection as described I the Study Medications and Drug Administration section The secondary goal is to determine doses that generate Treg cells or induce immune deviation from TH1 to TH2 type response The tertiary goals are to determine the presence or absence of antibody to human E-selectin P- selectin and L-selectin and the level of endothelial activation markers including von Willebrand factor soluble E-selectin VCAM-1 and Thrombomodulin
Objective The goals of the study are a to test whether repeated administration of low-dose intranasal E-selectin is safe and tolerable and b to test whether it can induce mucosal tolerance to this compound causing a shift of immune response from TH1 to TH2 type with production of Treg cells
Study Population The study population will include 3-50 patients depending on dose escalation events plus 0-8 replacement patients depending on the number of drop outs with recent 30 and 120 days occurrence of any type or location of stroke documented by CT or MRI The final number of patients will be determined by a dose escalation plan described below that may stop early in the accrual process should adverse events arise Since patients will be required to make serial visits to the NIH clinical center a functional recovery score of 0-2 on the modified Rankin Scale ie 0 no symptoms at all 2 slight disability unable to carry out all previous activities but able to look after own affairs without assistance is required for inclusion in this study
Study Design This is a single center Phase 1 open label dose escalation trial assessing safety profile of four doses of intranasal recombinant human E-selectin
Outcome Measures The primary goal of this study is to define the maximum tolerated dose of intranasal instillation of recombinant human E-selection as described I the Study Medications and Drug Administration section The secondary goal is to determine doses that generate Treg cells or induce immune deviation from TH1 to TH2 type response The tertiary goals are to determine the presence or absence of antibody to human E-selectin P- selectin and L-selectin and the level of endothelial activation markers including von Willebrand factor soluble E-selectin VCAM-1 and Thrombomodulin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-N-0293 | None | None | None |