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In remote preconditioning, ischemia in one organ protects distant organs from ischemic insults. e.g. brief induced limb ischemia protects the brain from an otherwise more severe stroke.
The objective of this study is to determine if remote ischemic preconditioning can be safely and effectively instituted in patients with subarachnoid hemorrhage, who are at high risk for developing disabling cerebral ischemia. The investigators will also preliminarily assess if there is evidence for neuroprotection. This will be a Phase 1b study.
Additional objectives are:
The investigators propose to study patients with subarachnoid hemorrhage, who generally have a high risk of ischemic stroke in the 2 weeks following the initial bleed, and patients with clipped or coiled aneurysm. The investigators will apply a blood pressure cuff around leg and use it to interrupt the circulation for 5-10 minutes. The investigators will repeat this for a total of 3 times every 24 to 48 hours up to 14 days. The cuff will be inflated for 5-10 minutes and then deflated for 5 minutes. There will be 3 cycles of this. The cuff will be inflated to 200mmHg.
The investigators will first start with 5 minutes of cuff inflation to either the arm or leg. The investigators will determine if this is safe in at least 6 patients. The investigators will then increase the duration of cuff inflation to 7.5 minutes for another 6 patients. If no adverse events are noted the investigators will the proceed to study 10 minutes of inflation in another 6 patients. If no side effects are noted the investigators will then determine that this is well tolerated.
The study will be monitored by a Data Safety Monitoring Board who will make decisions about escalating the duration of cuff inflation. If 2 or more patients develop an adverse event that is related to the procedure the investigators will stop and no longer continue at that level of cuff inflation and the previous level of cuff inflation will be determined to be the safe and tolerated level.
The investigators will collect safety data on adverse events such as tolerability, local tissue trauma or deep vein thrombosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| remote limb preconditioning | Experimental | Subjects with subarachnoid hemorrhage will undergo escalating times of limb ischemia to determine tolerability and safety. The leg will be made transiently ischemic with application of a blood pressure cuff for up to 3 cycles of 10 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| remote limb preconditioning | Procedure | 3 cycles of up to 10 minutes leg ischemia |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Deep Vein Thrombosis for Safety Assessment. | 90 days | |
| Visual Analog Scale Score as a Measure of Tolerability | The visual analogue scale is a pain scale from 0-10, with 10 being maximum pain and is frequently used in research studies assessing patient discomfort. | 90 days |
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Inclusion Criteria: aneurismal subarachnoid hemorrhage
Exclusion Criteria:
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Subjects admitted to a large community based teaching hospital were recruited between November 2008 and July 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sham Preconditioning | Subjects with subarachnoid hemorrhage will undergo escalating times of limb ischemia to determine tolerability and safety. The leg will be made transiently ischemic with application of a blood pressure cuff for up to 3 cycles of 10 minutes. A sham preconditioning group was added with only minimal cuff inflation. |
| FG001 | 5-min Ischemia | |
| FG002 | 7.5-min Ischemia | |
| FG003 | 10-min Ischemia |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sham Preconditioning |
|
| ||||||||||||||||||
| 5 Min Ischemia |
| |||||||||||||||||||
| 7.5 Min Ischemia |
| |||||||||||||||||||
| 10 Min Ischemia |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sham Preconditioning | Subjects with subarachnoid hemorrhage will undergo escalating times of limb ischemia to determine tolerability and safety. The leg will be made transiently ischemic with application of a blood pressure cuff for up to 3 cycles of 10 minutes. |
| BG001 | 5 Min Ischemia |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Deep Vein Thrombosis for Safety Assessment. | Posted | Jul 2010 | Number | participants | 90 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sham Preconditioning | Subjects with subarachnoid hemorrhage will undergo escalating times of limb ischemia to determine tolerability and safety. The leg will be made transiently ischemic with application of a blood pressure cuff for up to 3 cycles of 10 minutes. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Delayed cerebral ischemia | Nervous system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| hyponatremia | Metabolism and nutrition disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sebastian Koch | University Miami | 305 243-6733 | skoch@med.miami.edu |
| ID | Term |
|---|---|
| D013345 | Subarachnoid Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D019194 | Ischemic Preconditioning |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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| COMPLETED |
|
| NOT COMPLETED |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | 7.5 Min Ischemia |
| BG003 | 10 Min Ischemia |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Primary | Visual Analog Scale Score as a Measure of Tolerability | The visual analogue scale is a pain scale from 0-10, with 10 being maximum pain and is frequently used in research studies assessing patient discomfort. | We escalated the ischemia times in cohorts of 6. Cohorts of 6 were prespecified at the beginning to the study. All analysis was intention to treat | Posted | Mean | Standard Deviation | units on a scale | 90 days |
|
|
|
| 3 |
| 7 |
| 5 |
| 7 |
| EG001 | 5 Min Ischemia | 9 | 14 | 8 | 14 |
| EG002 | 7.5 Min Ischemia | 1 | 7 | 3 | 7 |
| EG003 | 10 Min Ischemia | 1 | 6 | 4 | 6 |
| low hematocrit | Blood and lymphatic system disorders |
|
| pulmonary edema | Respiratory, thoracic and mediastinal disorders |
|
| death | General disorders |
|
| ventriculitis | Infections and infestations |
|
| deep vein thrombosis | Vascular disorders |
|
| pneumonia | Infections and infestations |
|
| low hematocrit | Blood and lymphatic system disorders |
|
| urinary tract infection | Infections and infestations |
|
| hypoxemia | Respiratory, thoracic and mediastinal disorders |
|
| stridor | Respiratory, thoracic and mediastinal disorders |
|
| pulmonary edema | Respiratory, thoracic and mediastinal disorders |
|
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| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |