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Neuronal and Glial Biomarkers in Stroke

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ClinicalTrials.gov Identifier: NCT02409043
Recruitment Status : Completed
First Posted : April 6, 2015
Last Update Posted : September 11, 2017
Sponsor:
Information provided by (Responsible Party):
University of Florida

Brief Summary:
The purpose of this research study is to determine if there are molecules in the blood that indicate when a person has had a stroke, and what type of stroke they have had, so that appropriate treatment may be begun as soon as possible. This study is also being conducted to determine whether these molecules can help to predict long-term health following stroke. Some of these potential molecules, also called biomarkers, include Neuronal biomarker ubiquitin C-terminal hydrolase-L1 (UCH-L1), Glial markers such as glial fibrillary acidic protein (GFAP), and a neuroprotective enzyme called angiotensin converting enzyme 2 (ACE2), which has activity that has been shown to be helpful cardiovascular disease and shown to be altered in animal models of acute stroke, where it is also shown to provide neuronal protection.

Condition or disease Intervention/treatment
Stroke Other: Blood draw Other: Stroke blood draw

Detailed Description:

Research Plan Participants will be recruited from those presenting at Shands University of Florida (UF) hospital emergency room within the early hours after symptom onset, during which time a blood draw will be taken. Either in the emergency room, intensive care unit, or general hospital ward, a member of the study team will obtain informed consent for study participation within 24 hours of the first blood draw. The study team will provide the participant or legally authorized representative (LAR) with the consent form to read and will explain the study to the participant or LAR using the consent form as a guide. Time will be given to allow the participant or LAR to read the consent form and any questions will be answered. If the participant or LAR agrees to participate, then the study team member will have the participant sign the consent form and a copy of the signed form will be given for participants' records.

Study procedure: Information will be collected from medical records to determine the type and severity of stroke that the participant had and the time of stroke onset. Three 10cc samples of blood will be drawn from 90 participants with stroke (45 with ischemic stroke and 45 with hemorrhagic stroke). Samples of blood will also be drawn from 45 controls and 45 patients with stroke mimics, clinical symptoms that could be stroke but are determined to be due to another cause (e.g. transient ischemic attack). The first 10cc will be drawn within 18 hours of stroke onset and the second will be drawn 72 hours following stroke onset. The third will be obtained at the UF Neurology outpatient clinic 2-8 weeks after stroke. The first blood sample will be drawn during the initial evaluation in the ER prior to obtaining informed consent. This is due to the hectic ER environment and the need for the participant or LAR to be making serious medical decisions during this initial evaluation; factors which make this a non-ideal time to perform the informed consent process. The blood sample will then be stored using only the de-identified participant number for identification. Once the participant's condition has stabilized and no other serious medical decisions are being made, a study team member will approach the participant or LAR for the informed consent process as described above.

If the informed consent is obtained within 24 hours of obtaining the first blood sample then the participant will be enrolled in the study, the stored blood sample will be kept for further processing, the second and third blood samples will be drawn as previously described and testing for the aforementioned panel of biomarkers will be performed on the blood samples. If the participant or LAR declines to participate in the study or if informed consent is not obtained within 24 hours of the obtaining the first blood sample: 1) the stored blood sample will not be used for any purpose, 2) the stored blood sample will be completely destroyed within 24 hours of knowledge that the participant will not participate in the study and 3) no further blood samples will be obtained. Finally, participant's will be asked to complete a brief (less than 5 minute) phone survey 3 months after stroke to assess long-term stroke disability.


Study Type : Observational
Actual Enrollment : 99 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Neuronal and Glial Biomarkers in Stroke
Study Start Date : July 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Group/Cohort Intervention/treatment
Control
Non-stroke participants. Blood drawn for analysis of biomarkers.
Other: Blood draw
Blood drawn for comparison with other groups

Ischemic Stroke
Participants presenting at the University of Florida Shands Emergency Department with an ischemic stroke. Blood drawn at day 1, day 3, and at 2-8 weeks after stroke, NIH stroke scale scores, modified Rankin scale scores, and MRI infarct size assessed in hospital. 3 month modified Rankin scale score collected by phone interview.
Other: Stroke blood draw
Participants presenting at the University of Florida Shands Emergency Department with an ischemic stroke. Blood drawn at day 1, day 3, and at 2-8 weeks after stroke, NIH stroke scale scores, modified Rankin scale scores, blood pressure, MRI infarct volumes, and hospital length of stay taken from the medical records. 3 month modified Rankin scale score collected by phone interview.
Other Name: Information collection

Hemorrhagic Stroke
Participants presenting at the University of Florida Shands Emergency Department with an ischemic stroke. Blood drawn at day 1, day 3, and at 2-8 weeks after stroke, NIH stroke scale scores, modified Rankin scale scores, and MRI infarct size assessed in hospital. 3 month modified Rankin scale score collected by phone interview.
Other: Stroke blood draw
Participants presenting at the University of Florida Shands Emergency Department with an ischemic stroke. Blood drawn at day 1, day 3, and at 2-8 weeks after stroke, NIH stroke scale scores, modified Rankin scale scores, blood pressure, MRI infarct volumes, and hospital length of stay taken from the medical records. 3 month modified Rankin scale score collected by phone interview.
Other Name: Information collection

Stroke Mimic
Participants presenting at the University of Florida Shands Emergency Department with signs and symptoms resembling a stroke, but which are determined to be from another cause. Blood drawn during initial emergency room evaluation.
Other: Blood draw
Blood drawn for comparison with other groups




Primary Outcome Measures :
  1. Acute Serum ACE2 Activity Levels [ Time Frame: Day 1 ]
    Serum and whole blood will be analyzed for levels of ACE2 activity. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome.

  2. Subacute Serum ACE2 Activity Levels [ Time Frame: Day 3 ]
    Serum and whole blood will be analyzed for levels of ACE2 Activity.

  3. Follow-up Serum ACE2 Activity Levels [ Time Frame: 8 weeks ]
    Serum and whole blood will be analyzed for levels of ACE2 Activity. This last time point will be assessed after discharge from the hospital at the time that the patient returns to the UF Neurology Clinic for their follow-up visit.


Secondary Outcome Measures :
  1. Initial NIH Stroke Scale Score [ Time Frame: Day 1 ]
    NIH stroke scale scores will obtained as part of the normal care and are scored with points being assigned for neurological deficits (0 = best possible, highest number = best possible) in areas of motor control of the arm (0-4), leg (0-4) sensory perception (0-2), language (0-3), limb ataxia (0-2), gaze (0-2), level of consciousness (0-3), orientation (0-2), response to commands (0-2), facial palsy (0-3), visual (0-3), dysarthria (0-2), and extinction (0-2), and is used to assess the level of neurological deficit from the stroke.

  2. Recovery NIH Stroke Scale Score [ Time Frame: Day 14 ]
    NIH stroke scale scores will obtained as part of the normal care and are scored with points being assigned for neurological deficits (0 = best possible, highest number = best possible) in areas of motor control of the arm (0-4), leg (0-4) sensory perception (0-2), language (0-3), limb ataxia (0-2), gaze (0-2), level of consciousness (0-3), orientation (0-2), response to commands (0-2), facial palsy (0-3), visual (0-3), dysarthria (0-2), and extinction (0-2), and is used to assess the level of neurological deficit from the stroke.

  3. Initial infarct size from brain imaging studies [ Time Frame: Day 1 ]
    Infarct size will be measured as part of the normal care by MRI volumetric analysis in cm cubed and may range from less than a cm cubed to 20 cm cubed or greater depending on the extent of the stroke. This is meant to assess the size of the stroke.

  4. Recovery infarct size from brain imaging studies [ Time Frame: Day 14 ]
    Infarct size will be measured as part of the normal care by MRI volumetric analysis in cm cubed and may range from less than a cm cubed to 20 cm cubed or greater depending on the extent of the stroke. This is meant to assess the size of the stroke.

  5. Initial modified Rankin Score [ Time Frame: Day 1 ]

    Initial modified Rankin scale scores will be acquired in hospital as a part of the normal care and by a follow-up phone interview at 3 months. This is scored as follows:

    0 - No symptoms.

    1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
    2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
    3. - Moderate disability. Requires some help, but able to walk unassisted.
    4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
    5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
    6. - Dead.

  6. Recovery modified Rankin Score [ Time Frame: Day 14 ]

    Initial modified Rankin scale scores will be acquired in hospital as a part of the normal care and by a follow-up phone interview at 3 months. This is scored as follows:

    0 - No symptoms.

    1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
    2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
    3. - Moderate disability. Requires some help, but able to walk unassisted.
    4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
    5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
    6. - Dead.

  7. Long-term modified Rankin Score [ Time Frame: 3 months ]

    Initial modified Rankin scale scores will be acquired in hospital as a part of the normal care and by a follow-up phone interview at 3 months. This is scored as follows:

    0 - No symptoms.

    1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
    2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
    3. - Moderate disability. Requires some help, but able to walk unassisted.
    4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
    5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
    6. - Dead.

  8. Acute Serum GFAP Levels [ Time Frame: Day 1 ]
    Serum and whole blood will be analyzed for levels of GFAP. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome.

  9. Subacute Serum GFAP Levels [ Time Frame: Day 3 ]
    Serum and whole blood will be analyzed for levels of GFAP. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome.

  10. Follow-up Serum GFAP Levels [ Time Frame: 8 weeks ]
    Serum and whole blood will be analyzed for levels of GFAP. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome. This last time point will be assessed after discharge from the hospital at the time that the patient returns to the UF Neurology Clinic for their follow-up visit.

  11. Acute Serum UCH-L1 Levels [ Time Frame: Day 1 ]
    Serum and whole blood will be analyzed for levels of UCH-L1. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome.

  12. Subacute Serum UCH-L1 Levels [ Time Frame: Day 3 ]
    Serum and whole blood will be analyzed for levels of UCH-L1. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome.

  13. Follow-up Serum UCH-L1 Levels [ Time Frame: 8 weeks ]
    Serum and whole blood will be analyzed for levels of UCH-L1. These markers will be assessed for their value as biomarkers of stroke subtype and long-term outcome. This last time point will be assessed after discharge from the hospital at the time that the patient returns to the UF Neurology Clinic for their follow-up visit.


Biospecimen Retention:   Samples Without DNA
Serum and packed red blood cells


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Individuals experiencing stroke symptoms who present at the University of Florida Shands Emergency Department or non-stroke control participants. These individuals will be invited to participate as study participants by a study representative within the first 24 hours after having a blood draw in the emergency department.
Criteria

Inclusion Criteria:

  • Stroke, ischemic or hemorrhagic, is confirmed by clinical and/or imaging evidence
  • For control participants, no acute or recent stroke

Exclusion Criteria:

  • Onset of stroke symptoms cannot be confirmed to be less than 18 hours

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02409043


Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Harry Nick, PhD University of Florida

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02409043     History of Changes
Other Study ID Numbers: IRB201200330
First Posted: April 6, 2015    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:
Stroke
Ischemic stroke
Hemorrhagic stroke
Biomarkers
Angiotensins

Additional relevant MeSH terms:
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases