Date opened: May 7, 2014
Type: Cohort, observational, controlled.
Size: Single centre
Current status: Open
Recruitment to date: 67
Lead researchers: Prof Tony Belli
Through the collaboration of the University of Birmingham, University Hospitals Birmingham NHS Foundation Trust and Defence Scientific and Technology Laboratories, the aim of the Golden Hour study is to characterise the biomarker response to traumatic brain injury (TBI) and define the roles of biomarkers in injury detection, diagnosis, monitoring, classification, prognosis and treatment. This will form a basis for future interventional studies to improve outcome of TBI patients.
TBI remains a leading cause of morbidity and mortality in particular affecting the young with a male preponderance. At present, treatment is largely supportive and investigational techniques have not changed apace clinically despite numerous research efforts. A biomarker in the broadest sense is any characteristic that may be objectively assessed to provide an indicator of a normal or abnormal physiological state of an organism. This includes laboratory tests along with imaging and more simple clinical findings. Biomarkers are used in other clinical settings, such as Troponin for cardiac damage during heart attack. There has been increasing interest in the development of biomarkers for neurotrauma, although this has not yet led to a change in clinical practice. Previous research has assessed potential biomarkers including substances released generally in response to or as an effect of injury in this context, e.g. creatine kinase, glial fibrillary acidic protein, myelin basic protein and S100B. Studies conducted so far have not fully defined the role of biomarkers in clinical practice; few have made a transition to the bed side. The variety of biomarkers may be assayed in order to provide an insight into many factors surrounding an injury, such as severity and progression.
The Golden Hour study aims to improve on previous clinical studies by investigating a range of potential biomarkers in serum, brain tissue (through microdialysis if applicable), cerebrospinal fluid (CSF, if applicable) and imaging in TBI and non-TBI (i.e. other major trauma as control) patients with comprehensive outcome measures. In the long term we hope these biomarkers might improve the diagnosis, monitoring and prognostication of TBI thus allowing better targeted treatment and potentially revealing new avenues for management.
Who is eligible?
Patients are eligible to take part in this trial if they have sustained a major trauma and:
- Have blood samples taken within one hour of the injury (for the purpose of this study)
- Aged 18 or above
- Without any known long-term neurological conditions (such as brain tumour, multiple sclerosis, Alzheimer’s and Parkinson’s diseases, etc.)
Once a patient has been enrolled in the trial, blood samples will be taken at intervals during the first 3 days after the injury for biomarkers analysis. Microdialysis and CSF samples (if applicable) will also be collected during the first 2 weeks for the same purpose. A subgroup of patients will be selected to take part in advanced MRI scans (including MR spectroscopy and diffusion tensor imaging) within the first month of hospitalisation. Patients will be followed up at 6 and 12 months with further blood sampling, MRI scanning, neuropsychometric tests, transcranial magnetic stimulation and EEG recording, together with routine outcome assessments (functional status and self-reported outcome inventories) in the clinic.
Because most patients with a major trauma are unable to consent to taking part in a trial, consent will be sought from a family member at first. If no family member is available, a process can be used to obtain approval from a senior doctor who is not connected with the trial. This ensures that patients who cannot consent themselves and do not have a family member available are still entitled to the same level of access to this trial as any other patient. Informed consent will be sought from the patients themselves once they regain their consciousness and capacity when stable.
Patients’ progress will be monitored at set points post injury, with the aforementioned tests conducted at 6 and 12 months. Changes in biomarkers will be measured in relation to TBI versus non-TBI and correlate with the above outcome assessments. Formulating a better understanding of the relationships between severe TBI and biomarkers in development will improve clinical categorisation, assessments, prognostication and treatments, both in targeting existing interventions and through development of new treatment in future interventional studies. The serious nature of a major trauma means that some patients will not survive their injuries, but their participation in the trial still provides valuable information which will help save and improve lives around the world.