Traumatic Brain Injury Clinical Trials in Canada

Tight ankle muscles can produce ankle equinus (limited ability to pull the foot upward) and occur often in children, significantly impacting their ability to walk. If not treated, children with ankle equinus frequently experience reduced function and long-term foot problems, such as pain. Currently, treatment options include surgery or Botulinum toxin (BoNTA) injection into the large calf muscles that point the foot downwards, aiming to reduce their tightness. However, these treatments can be less effective over time, can create prolonged calf weakness, and may require long-term bracing. Another small muscle in the leg, the plantaris, is believed to have some contribution to equinus in many children. It is sometimes included in treatment plans for equinus but its contribution is poorly understood. It is unclear whether targeting the plantaris alone could lead to better treatment of ankle equinus. Understanding the effect of treatments targeting the plantaris could help clinicians improve the management of ankle equinus. In this study, we will look at the impact of surgical treatment to the plantaris in ankle equinus. We hypothesize that the plantaris is a significant contributor to equinus. Data will be collected from 42 children undergoing surgical intervention for ankle equinus. Subjects will be randomly allocated into two groups of equal size: 1) plantaris lengthened before the lengthening in the gastrocsoleus and 2) plantaris lengthened after gastrocsoleus lengthening. All surgical procedures for each patient will be completed in a single setting. Ankle range of motion will be measured at several intervals during surgery. We will measure the same outcome in each group. The outcome is maximum passive ankle dorsiflexion (upwards bend of the ankle) with the knee straight. We expect that maximum passive ankle dorsiflexion will significantly increase after lengthening of the plantaris. Understanding the contribution of the plantaris muscle in ankle equinus could lead to significant improvements in the treatment of children with tight ankles. Read Less

There are no therapeutic agents that have been shown to improve outcomes from severe traumatic brain injury (TBI). Critical barriers to progress in developing treatments for severe TBI are the lack of: 1) monitoring biomarkers for assessing individual patient response to treatment; 2) predictive biomarkers for identifying patients likely to benefit from a promising intervention. Currently, clinical examination remains the fundamental tool for monitoring severe TBI patients and for subject selection in clinical trials. However, these patients are typically intubated and sedated, limiting the utility of clinical examinations. Validated monitoring and predictive biomarkers will allow titration of the dose of promising therapeutics to individual subject response, as well as make clinical trials more efficient by enabling the enrollment of subjects likely to benefit. Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and high sensitivity c-reactive protein (hsCRP) are promising biomarkers that may be useful as 1) monitoring biomarkers; 2) predictive biomarkers in severe TBI trials. Although the biological rationale supporting their use is strong, significant knowledge gaps remain. To address these gaps in knowledge, we propose an ancillary observational study leveraging an ongoing severe TBI clinical trial that is not funded to collect biospecimen. The Hyperbaric Oxygen in Brain Injury Treatment (HOBIT) trial, a phase II randomized control clinical trial that seeks to determine the dose of hyperbaric oxygen therapy (HBOT) that that has the highest likelihood of demonstrating efficacy in a phase III trial. The proposed study will: 1) validate the accuracy of candidate monitoring biomarkers for predicting clinical outcome; 2) determine the treatment effect of different doses of HBOT on candidate monitoring biomarkers; and 3) determine whether there is a biomarker defined subset of severe TBI that responds favorably to HBOT. This proposal will: 1) inform a go/no-go decision for a phase III trial of HBOT by providing adjunctive evidence of the effect of HBOT on key biological pathways through which HBOT is hypothesized to affect outcome; 2) provide evidence to support further study of the first monitoring biomarkers of severe TBI; 3) increase the likelihood of success of a phase III trial by identifying the sub-population of severe TBI likely to benefit from HBOT; 4) create a repository of TBI biospecimen which may be accessed by other investigators. This study is related to NCT04565119 Read Less

Our project aims to develop a rapidly acquired and communicated MRI assessment and report that incorporates functional and structural imaging to convey information about functional neurological insults following traumatic brain injury (TBI) that are not typically visible on clinical imaging. Within this framework, there are two sub-studies. The first is a prospective study of patients with TBI who will have an MRI in the sub-acute period after their injury, followed by clinical assessments up to 90 days post-injury. A model will be developed to link MRI biomarkers to persistent symptoms of TBI. The second sub-study will use a focus group methodology to develop the report content and format with input from several groups of stakeholders. Read Less

This is a phase III, multi-centre, double blind, randomized controlled trial of patients with traumatic brain injury (TBI). Read Less

The research project aims to better understand the multiple factors related to the clinical evolution and the social participation of traumatic brain injured (TBI). The project will provide better understanding of the patients' evolution during rehabilitation after TBI in terms of adaptation and social participation, assess the effect of rehabilitation and study social participation outcomes and quality of life of TBI patients one-year post-rehabilitation. Project benefits include improvement of clinical practices and support in decision-making. The objectives of this research project are: Part 1: To provide a picture of the evolution, in terms of social adaptation and participation of patients during rehabilitation after a TBI. Part 2: To study social participation outcomes and quality of life of TBI individuals one year after the end of their rehabilitation. Read Less

The goal is to derive and a clinical decision rule for safe exclusion of traumatic brain injury without neuroimaging in head-injured ED patients who take anticoagulant medications. The objectives are to: 1. Derive and externally validate a new highly sensitive and maximally specific clinical decision rule for the exclusion of traumatic brain injury in head-injured ED patients who take anticoagulant medications; and, 2. Estimate the sensitivity and specificity of existing head injury clinical decision rules in head-injured ED patients who take anticoagulant medications. Read Less

The purpose of this innovative adaptive phase II trial design is to determine the optimal combination of hyperbaric oxygen treatment parameters that is most likely to demonstrate improvement in the outcome of severe TBI patients in a subsequent phase III trial. Read Less

The goal of this study is to establish the feasibility of an intervention designed to improve memory in patients who have experienced a moderate or severe traumatic brain injury (m-sTBI) and to examine its effect on brain structures. Read Less

The NeurO2 study is a multicenter observational study looking at NIRS monitoring in neurocrocritically ill patients during the acute phase of care following an acute brain injury. The study is nested within the HEMOTION Trial and the SAHaRA Trial Read Less