Ignite Creation Date:
2024-05-06 @ 6:12 PM
Last Modification Date:
2024-10-26 @ 2:44 PM
Study NCT ID:
NCT05588115
Status:
NOT_YET_RECRUITING
Last Update Posted:
2022-11-04
First Post:
2022-10-04
Brief Title:
Rapid Accurate Cost-effective Assessment of Blood Biomarkers for Diagnosis of Concussion
Sponsor:
University of Calgary
Organization:
University of Calgary
Study Overview
Official Title:
RACE Study Rapid Accurate and Cost-effective Analysis of Glial Fibrillary Acid Protein Using a Hand-held Biosensor for Patient With Concussion in Acute Care and at Home Monitoring
Status:
NOT_YET_RECRUITING
Status Verified Date:
2022-09
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:
RACE
Brief Summary:
The goal of this observational study is to test if a biosensor can accurately measure a blood biomarker in adult patients presenting to the emergency department with concussion The main questions it aims to answer are
Does the biosensor measure the blood biomarker of interest with the same accuracy as the current gold-standard assay technique
Do relationships exist between blood biomarker measurements from the biosensor and any psychological or physical symptoms of concussion
Participants will be asked to provide blood samples at initial visit and 2- 6- and 12-weeks after injury while completing questionnaires at each visit along with a brief 2 min daily symptom inventory
Researchers will compare the concussion group to a muscleskeletal injury group to see if measurements from the biosensor are exclusive to concussion
Does the biosensor measure the blood biomarker of interest with the same accuracy as the current gold-standard assay technique
Do relationships exist between blood biomarker measurements from the biosensor and any psychological or physical symptoms of concussion
Participants will be asked to provide blood samples at initial visit and 2- 6- and 12-weeks after injury while completing questionnaires at each visit along with a brief 2 min daily symptom inventory
Researchers will compare the concussion group to a muscleskeletal injury group to see if measurements from the biosensor are exclusive to concussion
Detailed Description:
BACKGROUND
It is estimated 100-300100000 people worldwide present to a hospital with traumatic brain injury TBI annually the majority of which are classified as mild TBI is a disruption in normal brain function caused by external biomechanical forces transmitted directly or indirectly to the head and is a leading cause of death and disability in Canada Approximately 1 in 450 Canadians report brain injury as their most significant injury associated with disability in the previous year Mild traumatic brain injury mTBI is operationalized under clinical severity by a Glasgow Coma Scale GCS score of 13-15 and is often used interchangeably with concussion though the most recent consensus definition of concussion is precluded by positive findings on standard neuroimaging techniques Although labelled as mild with typical recovery times within two weeks of injury for adults and four weeks for youth up to 30 of patients with concussion experience prolonged symptoms headache fatigue dizziness insomnia depression anxiety poor balance and cognitive deficits etc contributing to significant functional impairment and disease burden Furthermore in 2016 approximately 10 of diagnosed concussions in Ontario returned to the emergency department within 14 days of injury increasing demands on the health care system
Lending to its identity as one of the most complex injuries to diagnose and manage concussion currently relies on subjective measures and symptom reports as clinical indices of injury There has been accelerated interest in addressing this limitation through research efforts working to establish objective measures of injury including advanced neuroimaging imaging techniques machine learning of basic physiological functions brain waves heart rate blood pressure etc and blood biomarkers Blood biomarkers have shown promising results regarding their ability to detect or predict severe and moderate TBI but results in mTBI are mixed and require further investigation Two biomarkers of brain injury - glial fibrillary acidic protein GFAP and ubiquitin c-terminal hydrolase L1 UCH-L1 - were recently FDA approved to help identify necessity of a CT scan for adult mTBI patients who might have intracranial lesions However beyond the currently insufficient level of evidence regarding blood biomarker applications for concussion diagnosis or prognosis an additional hurdle for future implementation in a clinical setting remains the high cost and time-consuming assay methodologies for marker detection Single molecule array technology SIMOA is a fully automated immunoassay capable of biomarker detection at the femtogram level approximately 900x more sensitive than conventional enzyme-linked immunosorbent assays As the current gold-standard for low concentration biomarker detection significant monetary and procedural costs may limit SIMOAs future applications for concussion biomarker detection in clinical settings Fortunately technological advancements are pushing the boundaries of conventional assay approaches to minimize cost and maximize efficiency progressing towards point-of-care assay devices
The investigators have developed a GFAP nano-biosensor capable of measuring GFAP concentrations in similar orders of magnitude as SIMOA Briefly the GFAP electrochemical biosensor was developed using nano-porous carbon on screen-printed electrodes with hydroxylamine NH2OH The nano-coated and functionalized electrodes were immobilized with monoclonal anti-human GFAP capture antibody then blocked with bovine serum albumin GFAP binding frequency was translated to serum concentration levels using electrochemical impedance spectroscopy EIS The nano-porous biosensor provided ultrasensitive GFAP detection in a wide operational range of 100 fgmL - 10 ngmL concentrations in the human serum It selectively detected GFAP when tested against other biomarkers released after brain injury and revealed a clinical sensitivity for detection of patients across TBI severities total n70 TBI n26 healthy control n44 at 8462 95CI 651 to 956 and specificity at 6136 CI 455 to 756 The limit of detection of the GFAP biosensor was measured to be 866 fgmL in serum Additionally our nano-biosensor demonstrated 2 intra-variation and 1 inter-variation tackling the concern of reproducible biosensor production needed for clinical detection This research seeks to validate the nano-biosensor in concussion patients presenting to the Emergency Department
OBJECTIVES
Primary Aim Establish the clinical accuracy of the GFAP nano-biosensor in patients with concussion presenting to the emergency department from diagnosis to recovery Secondary Aim Assess sensitivity and specificity of the GFAP nano-biosensor for identification of concussion by comparing concussion patients to musculoskeletal MSK injury controls Tertiary Aim Assess relationships between GFAP nano-biosensor concentrations and psychological depression anxiety physical headache sleep disturbances etc symptoms of concussion from diagnosis to recovery Quaternary aim Assess correlation between female menstrual cycle hormone concentrations progesterone estrogen and GFAP nano-biosensor concentrations
METHODS
This study has a recruitment target of 150 equal sex representation acute concussion patients presenting to the emergency department ED at foothills medical centre ages 18 through 65 Additionally a group of 75 equal sex representation musculoskeletal MSK injury controls will be recruited from the same ED within the same age range In a repeated measures prospective cohort design concussion patients will complete an initial visit within 1 week of injury then follow-up visits at 2- 6- and 12-weeks post-injury or until recovered Control MSK patients will complete all measures at a single visit Concussion patients who are not recovered by 12 weeks post-injury will be asked to complete questionnaires at 6 months post-injury Study measures include clinical outcome assessments of quality of life global health depression anxiety sleep and concussion symptoms along with blood draws Concussion patients will be asked to complete the post concussion symptom scale PCSS daily via an online link sent to them each morning to monitor recovery For the purposes of this study a patient will be deemed recovered if all symptoms have resolved and indicating 100 on a sliding scale that asks how recovered the patient feels from the concussion All other questionnaires will be completed prior to initial and follow-up blood draws Researchers will also be providing concussion patients with a QR code linked to the investigators website where patients will have access to concussion education resources to understand the injury The two assay techniques will be compared using mean detection and distribution curves and Bland-Altman analysis The performance of the GFAP biosensing kit in detection of uncomplicated concussion patients and monitoring their recovery will be assessed in plasma and serum The clinical sensitivity and specificity of the GFAP biosensor in plasma and serum will be evaluated using the receiver operating characteristic ROC curve in comparison to SIMOA
It is estimated 100-300100000 people worldwide present to a hospital with traumatic brain injury TBI annually the majority of which are classified as mild TBI is a disruption in normal brain function caused by external biomechanical forces transmitted directly or indirectly to the head and is a leading cause of death and disability in Canada Approximately 1 in 450 Canadians report brain injury as their most significant injury associated with disability in the previous year Mild traumatic brain injury mTBI is operationalized under clinical severity by a Glasgow Coma Scale GCS score of 13-15 and is often used interchangeably with concussion though the most recent consensus definition of concussion is precluded by positive findings on standard neuroimaging techniques Although labelled as mild with typical recovery times within two weeks of injury for adults and four weeks for youth up to 30 of patients with concussion experience prolonged symptoms headache fatigue dizziness insomnia depression anxiety poor balance and cognitive deficits etc contributing to significant functional impairment and disease burden Furthermore in 2016 approximately 10 of diagnosed concussions in Ontario returned to the emergency department within 14 days of injury increasing demands on the health care system
Lending to its identity as one of the most complex injuries to diagnose and manage concussion currently relies on subjective measures and symptom reports as clinical indices of injury There has been accelerated interest in addressing this limitation through research efforts working to establish objective measures of injury including advanced neuroimaging imaging techniques machine learning of basic physiological functions brain waves heart rate blood pressure etc and blood biomarkers Blood biomarkers have shown promising results regarding their ability to detect or predict severe and moderate TBI but results in mTBI are mixed and require further investigation Two biomarkers of brain injury - glial fibrillary acidic protein GFAP and ubiquitin c-terminal hydrolase L1 UCH-L1 - were recently FDA approved to help identify necessity of a CT scan for adult mTBI patients who might have intracranial lesions However beyond the currently insufficient level of evidence regarding blood biomarker applications for concussion diagnosis or prognosis an additional hurdle for future implementation in a clinical setting remains the high cost and time-consuming assay methodologies for marker detection Single molecule array technology SIMOA is a fully automated immunoassay capable of biomarker detection at the femtogram level approximately 900x more sensitive than conventional enzyme-linked immunosorbent assays As the current gold-standard for low concentration biomarker detection significant monetary and procedural costs may limit SIMOAs future applications for concussion biomarker detection in clinical settings Fortunately technological advancements are pushing the boundaries of conventional assay approaches to minimize cost and maximize efficiency progressing towards point-of-care assay devices
The investigators have developed a GFAP nano-biosensor capable of measuring GFAP concentrations in similar orders of magnitude as SIMOA Briefly the GFAP electrochemical biosensor was developed using nano-porous carbon on screen-printed electrodes with hydroxylamine NH2OH The nano-coated and functionalized electrodes were immobilized with monoclonal anti-human GFAP capture antibody then blocked with bovine serum albumin GFAP binding frequency was translated to serum concentration levels using electrochemical impedance spectroscopy EIS The nano-porous biosensor provided ultrasensitive GFAP detection in a wide operational range of 100 fgmL - 10 ngmL concentrations in the human serum It selectively detected GFAP when tested against other biomarkers released after brain injury and revealed a clinical sensitivity for detection of patients across TBI severities total n70 TBI n26 healthy control n44 at 8462 95CI 651 to 956 and specificity at 6136 CI 455 to 756 The limit of detection of the GFAP biosensor was measured to be 866 fgmL in serum Additionally our nano-biosensor demonstrated 2 intra-variation and 1 inter-variation tackling the concern of reproducible biosensor production needed for clinical detection This research seeks to validate the nano-biosensor in concussion patients presenting to the Emergency Department
OBJECTIVES
Primary Aim Establish the clinical accuracy of the GFAP nano-biosensor in patients with concussion presenting to the emergency department from diagnosis to recovery Secondary Aim Assess sensitivity and specificity of the GFAP nano-biosensor for identification of concussion by comparing concussion patients to musculoskeletal MSK injury controls Tertiary Aim Assess relationships between GFAP nano-biosensor concentrations and psychological depression anxiety physical headache sleep disturbances etc symptoms of concussion from diagnosis to recovery Quaternary aim Assess correlation between female menstrual cycle hormone concentrations progesterone estrogen and GFAP nano-biosensor concentrations
METHODS
This study has a recruitment target of 150 equal sex representation acute concussion patients presenting to the emergency department ED at foothills medical centre ages 18 through 65 Additionally a group of 75 equal sex representation musculoskeletal MSK injury controls will be recruited from the same ED within the same age range In a repeated measures prospective cohort design concussion patients will complete an initial visit within 1 week of injury then follow-up visits at 2- 6- and 12-weeks post-injury or until recovered Control MSK patients will complete all measures at a single visit Concussion patients who are not recovered by 12 weeks post-injury will be asked to complete questionnaires at 6 months post-injury Study measures include clinical outcome assessments of quality of life global health depression anxiety sleep and concussion symptoms along with blood draws Concussion patients will be asked to complete the post concussion symptom scale PCSS daily via an online link sent to them each morning to monitor recovery For the purposes of this study a patient will be deemed recovered if all symptoms have resolved and indicating 100 on a sliding scale that asks how recovered the patient feels from the concussion All other questionnaires will be completed prior to initial and follow-up blood draws Researchers will also be providing concussion patients with a QR code linked to the investigators website where patients will have access to concussion education resources to understand the injury The two assay techniques will be compared using mean detection and distribution curves and Bland-Altman analysis The performance of the GFAP biosensing kit in detection of uncomplicated concussion patients and monitoring their recovery will be assessed in plasma and serum The clinical sensitivity and specificity of the GFAP biosensor in plasma and serum will be evaluated using the receiver operating characteristic ROC curve in comparison to SIMOA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None