Mild Traumatic Brain Injury, Traumatic Brain Injury
Conditions
Keywords
TBI, mTBI, MR, MRI, Pulse Sequences, NFL
Brief summary
This feasibility study is being conducted to determine potential associations between a broad range of clinical neurological symptoms and magnetic resonance images (MRI), data, and clinical findings involved in mild traumatic brain injury (mTBI). These associations will be examined over the acute and sub-acute period (approximately 3 months) following injury to provide information useful for optimization of MR pulse sequences for mTBI applications. Correlations exist over the sub-acute period in clinical neurological and MR data (images, image reads, and RAW data), which may indicate temporal evolution patterns. The intent of this study is to broadly generate potential biomarkers of temporal evolution of mTBI detectable in MR images and data (MR mTBI biomarkers).
Detailed description
This hypothesis-generating feasibility study is being conducted to determine potential associations between a broad range of clinical neurological symptoms and MR images, data, and clinical findings involved in mild traumatic brain injury (mTBI). These associations will be examined over the acute and sub-acute period (approximately 3 months) following injury to provide information useful for optimization of MR pulse sequences for mTBI applications. The intent of this study is to broadly generate a range of potential mTBI biomarkers detectable using investigational MR pulse sequence technologies. Feasibility data attained in this study may be used for engineering program decision-making and in support of future scientific assessment, engineering development, published research databases or registries mTBI data and images, and other purposes determined by the Sponsor. The results of this study are not intended for use in regulatory submissions. Subjects will be examined on commercially available MR scanners using investigational or standard of care MR coils and a series of investigational MR Pulse Sequence sets (Application Packs). Each Application Pack will consist of a predetermined sequence of investigational pulse sequences (IPSs) optimized by GE Healthcare (GEHC) for mTBI. IPSs will be administered in a predetermined order as part of each Application Pack.
Interventions
DEVICEMRI
MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects
Sponsors
GE Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Segment 1: Inclusion Criteria for mTBI subjects Subjects included in the main part of this study (Segment 1) will: 1. Be aged ≥15 and ≤50 years old at the time of enrollment; 2. Be diagnosed with mTBI according to the standard diagnostic procedures at the investigational site in a timeframe that meets enrollment criteria for enrollment in one of the first two intervals of the study, as follows: 1. Meets criteria for enrollment in Encounter 1 (within 72 hours) OR 2. Meets criteria for enrollment in Encounter 2 (within 8±2 days) 3. Be capable of sufficiently clear communication to allow the subject to provide written informed consent, or assent with parental or guardian consent for minors as described in Section 6.3 - Protection of Vulnerable Subjects, for participation in all parts of the study. Segment 1:
Exclusion criteria
for mTBI subjects Subjects will be excluded that have: 1. Loss of consciousness (LOC) ≥15 minutes; 2. Posttraumatic amnesia lasting ≥24 hr following a recent TBI event; 3. Diagnosis of moderate to severe TBI or GCS \<13; 4. Structural brain injury indicated by previous neuroimaging findings; 5. Previous history of moderate to severe TBI; 6. Any previous history of mild TBI within the past 12 months; 7. Previously diagnosed brain white matter disease; 8. History of seizures within the past 10 years; 9. History of self-reported illicit drug abuse (except marijuana) in past 10 years; 10. History of alcohol abuse or dependence (per DSM-IV-TR Diagnostic Criteria); 11. Current primary Axis I or II psychiatric disorders, except for disorders classified as minor and not expected to impact study conduct or integrity (as detailed in Appendix D - Screening for Exclusion based on Axis I or II Disorders): 12. History of brain mass 13. History of neurosurgery 14. History of stroke 15. History of dementia 16. Known cognitive dysfunction 17. Known structural brain disease or malformation 18. Current anti-psychotic or antiepileptic medication usage 19. That are unable or unwilling to complete study procedures accurately or have any conflict of interest that could affect study results, in the opinion of the investigator; 20. Contraindications to MRI scanning, including: 1. Current or suspected pregnancy per site clinical practice; 2. Other conditions that may constitute a hazard to the subject during study participation, determined by the investigator; 3. Inability to comply with any part of the site's MR safety policy. Inclusion Criteria for Non-TBI subjects (Segment 2) All included subjects will: 1. Aged ≥15 and ≤50 years old at the time of enrollment; 2. Be well matched to one or more mTBI patients in Segment 1, in the opinion of the Principal Investigator, with regards to: 1. Age, 2. Gender, 3. Sociodemographic characteristics, and 4. Handedness. 3. Be capable of sufficiently clear communication to allow the subject to provide written informed consent, or assent with parental or guardian consent for minors as described in Section 6.3 - Protection of Vulnerable Subjects, for participation in all parts of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software | Per-patient 1 to 3 months, until dataset completion 1 yr | To determine associations between clinical neurological data, MR images, quantitative data from novel software post-processing (sponsor developed software including volumetry, Resting State \[RS\] functional magnetic resonance imaging \[fMRI\], kurtosis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Demographics | Per-patient 1 to 3 months, until dataset completion 1 yr | To comprehensively collect subject information (i.e. baseline health data, demographics, socioeconomics, injury presentation, post-injury status, and injury type, place, and cause) for mTBI subjects in context of MRI data. |
| Operator Set MRI Parameters | Per-patient 1 to 3 months, until dataset completion 1 yr | To record operator-adjusted parameters of the novel software on the MRI system |
Countries
United States
Participant flow
Pre-assignment details
Volunteer Control participants were scanned only for the purpose of operator training and calibrating the MRI device. No data was collected from these participants for the purpose of analysis.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Diagnostic mTBI MRI Diagnostic of subjects with mild Tramatic Brain Injury (mTBI)
MRI: MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects | 86 |
| Experimental: Diagnostic Non mTBI MRI Diagnostic of Non injured subjects that are closely matched to mTBI
MRI: MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects | 26 |
| Volunteers MRI Diagnostic of Volunteer Controls for Device Calibration
MRI: MR Diagnostic Imaging will be performed on both TBI subjects and Non TBI subjects | 0 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 29 | 1 | 0 |
| Overall Study | Writhdrawal due to early termination | 9 | 0 | 0 |
Baseline characteristics
| Characteristic | Experimental: Diagnostic mTBI | Experimental: Diagnostic Non mTBI | Volunteers | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 41 Participants | 6 Participants | 0 Participants | 47 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 20 Participants | 0 Participants | 65 Participants |
| Region of Enrollment United States | 86 Participants | 26 Participants | 0 Participants | 112 Participants |
| Sex: Female, Male Female | 40 Participants | 13 Participants | 0 Participants | 53 Participants |
| Sex: Female, Male Male | 46 Participants | 13 Participants | 0 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 86 | 0 / 26 | 0 / 0 |
| other Total, other adverse events | 1 / 86 | 0 / 26 | 0 / 0 |
| serious Total, serious adverse events | 0 / 86 | 0 / 26 | 0 / 0 |
Outcome results
Primary
mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software
To determine associations between clinical neurological data, MR images, quantitative data from novel software post-processing (sponsor developed software including volumetry, Resting State \[RS\] functional magnetic resonance imaging \[fMRI\], kurtosis).
Time frame: Per-patient 1 to 3 months, until dataset completion 1 yr
Population: Study was terminated and no subject outcome data were collected
| Arm | Measure | Value |
|---|---|---|
| Experimental: Diagnostic mTBI | mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software | 0 |
| Experimental: Diagnostic Non mTBI | mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software | 0 |
| Volunteers | mTBI Progression Indicated by Clinical Neurological Characteristics, MRI Images, and Quantitative MRI Data From Novel Software | 0 |
Secondary
Operator Set MRI Parameters
To record operator-adjusted parameters of the novel software on the MRI system
Time frame: Per-patient 1 to 3 months, until dataset completion 1 yr
Population: Study was terminated and no subject outcome data were collected
| Arm | Measure | Value |
|---|---|---|
| Experimental: Diagnostic mTBI | Operator Set MRI Parameters | 0 |
| Experimental: Diagnostic Non mTBI | Operator Set MRI Parameters | 0 |
| Volunteers | Operator Set MRI Parameters | 0 |
Secondary
Subject Demographics
To comprehensively collect subject information (i.e. baseline health data, demographics, socioeconomics, injury presentation, post-injury status, and injury type, place, and cause) for mTBI subjects in context of MRI data.
Time frame: Per-patient 1 to 3 months, until dataset completion 1 yr
Population: Study was terminated and no subject outcome data were collected
| Arm | Measure | Value |
|---|---|---|
| Experimental: Diagnostic mTBI | Subject Demographics | 0 |
| Experimental: Diagnostic Non mTBI | Subject Demographics | 0 |
| Volunteers | Subject Demographics | 0 |