Ignite Creation Date:
2024-05-06 @ 3:48 AM
Last Modification Date:
2024-10-26 @ 11:39 AM
Study NCT ID:
NCT02389647
Status:
COMPLETED
Last Update Posted:
2019-10-29
First Post:
2015-03-10
Brief Title:
Identification of Novel Molecular Markers for Cerebral Ischemia From Patients With Minor and Devastating Ischemic Injury
Sponsor:
St Josephs Hospital and Medical Center Phoenix
Organization:
St Josephs Hospital and Medical Center Phoenix
Study Overview
Official Title:
Identification of Novel Molecular Markers for Cerebral Ischemia From Patients With Minor and Devastating Ischemic Injury
Status:
COMPLETED
Status Verified Date:
2019-10
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:
The purpose of this study is to use an iatrogenic model of stroke meaning those strokes inadvertently caused by endovascular coiling of elective aneurysms to study the biology of stroke in humans
Detailed Description:
Ischemic stroke is one of the top causes of morbidity and mortality in the United States Despite a great deal of effort to improve outcomes of patients with ischemic cerebral strokes the lack of a bona fide animal model representative of cerebral ischemia in man makes the study of the pathological processes involved difficult Additionally the subtle but significant differences between biology of animal models and the biology of humans make translatability of animal results to humans difficult
The purpose of this study is to use an iatrogenic model of stroke meaning those strokes inadvertently caused by endovascular coiling of elective aneurysms to study the biology of stroke in humans Clinical evidence suggests that simple catheterization of cerebral vasculature causes small usually clinically silent embolic strokes These strokes are evident on MRI scans Additionally since the practitioner knows the onset of an interventional procedure he by default knows the timing of injury This simple model allows one to study stroke in real-time with knowledge of the time of onset Magnetic resonance imaging MRI evaluation allows the practitioner to identify the volume of stroke caused by the intervention Alternatively patients who present to the emergency room with large ischemic infarcts provide a natural control population for this study These patients present with large usually devastating strokes In most cases the timing of the onset of deficit is known The investigators propose to use the simple model of ischemia from endovascular interventions with the more obvious devastating cases of ischemic stroke who present to the emergency room to better understand the molecular pathways involved in stroke
Rationale Global analysis of biological markers is an established mechanism to study complex disease processes The introduction of microarray technology and systems wide analysis has improved the understanding of various biological and disease processes This revolution has been ongoing since the early 1990s The rationale for performing these studies is to augment the understanding of the basic mechanisms of stroke in humans As previously mentioned there is no bona fide model of stroke and the researchers experimental design provides a rather simple in human model for cerebral ischemia
The study requires four blood draws each 5 mL in volume blood draws are timed with normal times of blood draw these patients would be experiencing and do not place the patient at any additional risk
The blood samples will be analyzed as follows total ribonucleic acid RNA including the microRNA fraction and protein will be isolated and quantified from the blood samples The researchers will load the RNA samples onto Febit microRNA arrays The Febit miRNA chip has all of the known human miRNAs and miRNA star sequences from Sangers miRBase 14 With this platform total RNA is loaded directly onto the array There are no RNA labeling or amplification steps miRNA hybridization on the chip is followed by a microfluidic primer extension assay In this case only hybridization of the correct miRNA to the probe allows the primer extension step to proceed efficiently giving the array high sensitivity and specificity In addition the researchers have created custom microarrays adding several spike-in controls Our spike-ins provide feedback on the variability in RNA isolation and are an additional signal for array normalization The protein fraction will be analyzed using Ray Biotechs Quantibody Arrays These are arrays of antibodies that are designed to capture specific protein species the researchers will target approximately 120 unique proteins in a fully quantitative fashion These arrays essentially function as the traditional enzyme-linked immunosorbent assay ELISA but on a glass slide substrate The assays offer several advantages over ELISAs including the requirement for very low amounts of sample input but perhaps more importantly they facilitate the quantitative investigation of hundreds of proteins at once and therefore greatly accelerate the ability to search for and identify protein-based signatures andor biomarkers The data will be statistically analyzed using statistical tools that are deemed appropriate at the time of data analysis by investigators from TGen and Dr Kalani Drs Kalani and Nakaji will then correlate the identity and quantity of identified molecular markers their temporal appearance concentration and disappearance to the collected clinical data
A neuroradiologist will perform evaluation and interpretation of the computerized axial tomography CTMRI scans collected during the subjects inpatient stay and outpatient visits The neuroradiologist will be recording size and caliber of the blood vessels looking for malformations dissections aneurysms or other abnormalities
The researchers will also correlate the level of identified markers to how well the patient performs upon discharge from the hospital and at followup for up to two years from discharge using Modified Rankin Scale scores and Glasgow Outcome Scale GOS As a part of followup researcher will assess time to return to work if applicable complaints results of followup laboratory complete blood counts coagulation studies response to anti-platelet medications including aspirin resistance assay and the p2yp12 assays and basic metabolic panels and imaging and an updated complete history and physical to identify new conditions that may have resulted post-ischemia This information will be collected at the time of followup with the neurosurgeons Once this is done if a candidate microRNA or protein is identified the researchers will share the results again in a manner that excludes any patient specific information with our collaborators Department of Health and Human Services associated organizations such as the NIH
The purpose of this study is to use an iatrogenic model of stroke meaning those strokes inadvertently caused by endovascular coiling of elective aneurysms to study the biology of stroke in humans Clinical evidence suggests that simple catheterization of cerebral vasculature causes small usually clinically silent embolic strokes These strokes are evident on MRI scans Additionally since the practitioner knows the onset of an interventional procedure he by default knows the timing of injury This simple model allows one to study stroke in real-time with knowledge of the time of onset Magnetic resonance imaging MRI evaluation allows the practitioner to identify the volume of stroke caused by the intervention Alternatively patients who present to the emergency room with large ischemic infarcts provide a natural control population for this study These patients present with large usually devastating strokes In most cases the timing of the onset of deficit is known The investigators propose to use the simple model of ischemia from endovascular interventions with the more obvious devastating cases of ischemic stroke who present to the emergency room to better understand the molecular pathways involved in stroke
Rationale Global analysis of biological markers is an established mechanism to study complex disease processes The introduction of microarray technology and systems wide analysis has improved the understanding of various biological and disease processes This revolution has been ongoing since the early 1990s The rationale for performing these studies is to augment the understanding of the basic mechanisms of stroke in humans As previously mentioned there is no bona fide model of stroke and the researchers experimental design provides a rather simple in human model for cerebral ischemia
The study requires four blood draws each 5 mL in volume blood draws are timed with normal times of blood draw these patients would be experiencing and do not place the patient at any additional risk
The blood samples will be analyzed as follows total ribonucleic acid RNA including the microRNA fraction and protein will be isolated and quantified from the blood samples The researchers will load the RNA samples onto Febit microRNA arrays The Febit miRNA chip has all of the known human miRNAs and miRNA star sequences from Sangers miRBase 14 With this platform total RNA is loaded directly onto the array There are no RNA labeling or amplification steps miRNA hybridization on the chip is followed by a microfluidic primer extension assay In this case only hybridization of the correct miRNA to the probe allows the primer extension step to proceed efficiently giving the array high sensitivity and specificity In addition the researchers have created custom microarrays adding several spike-in controls Our spike-ins provide feedback on the variability in RNA isolation and are an additional signal for array normalization The protein fraction will be analyzed using Ray Biotechs Quantibody Arrays These are arrays of antibodies that are designed to capture specific protein species the researchers will target approximately 120 unique proteins in a fully quantitative fashion These arrays essentially function as the traditional enzyme-linked immunosorbent assay ELISA but on a glass slide substrate The assays offer several advantages over ELISAs including the requirement for very low amounts of sample input but perhaps more importantly they facilitate the quantitative investigation of hundreds of proteins at once and therefore greatly accelerate the ability to search for and identify protein-based signatures andor biomarkers The data will be statistically analyzed using statistical tools that are deemed appropriate at the time of data analysis by investigators from TGen and Dr Kalani Drs Kalani and Nakaji will then correlate the identity and quantity of identified molecular markers their temporal appearance concentration and disappearance to the collected clinical data
A neuroradiologist will perform evaluation and interpretation of the computerized axial tomography CTMRI scans collected during the subjects inpatient stay and outpatient visits The neuroradiologist will be recording size and caliber of the blood vessels looking for malformations dissections aneurysms or other abnormalities
The researchers will also correlate the level of identified markers to how well the patient performs upon discharge from the hospital and at followup for up to two years from discharge using Modified Rankin Scale scores and Glasgow Outcome Scale GOS As a part of followup researcher will assess time to return to work if applicable complaints results of followup laboratory complete blood counts coagulation studies response to anti-platelet medications including aspirin resistance assay and the p2yp12 assays and basic metabolic panels and imaging and an updated complete history and physical to identify new conditions that may have resulted post-ischemia This information will be collected at the time of followup with the neurosurgeons Once this is done if a candidate microRNA or protein is identified the researchers will share the results again in a manner that excludes any patient specific information with our collaborators Department of Health and Human Services associated organizations such as the NIH
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 |
|---|---|---|---|
| 5UH2TR000891 | NIH | None | httpsreporternihgovquickSearch5UH2TR000891 |