With the generous support of the Rick Hansen Foundation, ICORD was able to award seven seed grants in the Fall 2020 competition. We are very grateful for this ongoing and extremely valuable support.
Quality of safety reporting in acute spinal cord injury clinical trials: a systematic review.
PI: Jacquelyn Cragg. Co-Investigator: John Kramer.
Large-scale clinical trials offer a unique opportunity to assess the safety of medical interventions in a controlled setting. Complete and accurate reporting of intervention-related adverse events and toxicity is essential to guide treatment decisions for acute spinal cord injury. However, inadequacies in the reporting of adverse events and toxicity has recently drawn attention in other fields. In the field of spinal cord injury, there are no comprehensive studies to date pertaining to the quality of safety reporting in acute trials. In a cursory analysis, we have observed inadequacies in reporting harms in acute spinal cord injury trials. Therefore, in the present seed project, we will extend our preliminary evaluation of safety reporting to a comprehensive systematic review of all completed acute clinical trials in spinal cord injury. In doing so, we will gain insight for improving deficiencies in reporting harms of potential treatments for acute spinal cord injury. Overall, this work will seed the future development of safety reporting guidelines in acute spinal cord injury.
Development of an upper limb muscle dynamometer to enable the objective assessment of SCI patient neuromusculoskeletal rehabilitation.
PI: Joshua Giles. Co-Investigator: Mike Berger
Some of the most devastating spinal cord injuries (SCI) lead to loss of upper limb function, resulting in the inability to use one’s upper limb and in the need for extensive assistance when performing basic daily tasks. Emerging treatments have shown promise in restoring function for these patients including through nerve transfer surgery where a still functional nerve is surgically transferred to “reanimate” a muscle group that had lost function. However, its is necessary to have high quality outcome measures that demonstrate improvement in muscle function to justify the widespread adoption of these experimental, complex, and often expensive treatments. Unfortunately, no testing system exists that is capable of accommodating the limitations of people with SCI while producing the high quality data necessary to support the clinical adoption of these treatments. Therefore, the goal of this project is to develop a mobile and easy to use muscle function assessment device, known as a dynamometer, tailored to the needs of evaluating 04/11/2020 people with SCI. This development project will be led by a biomechanics and mechanical engineering design professor in collaboration with a SCI and rehabilitation physician/researcher who are both active ICORD members.
Deriving a clinic-ready formulation of antibiotic sulfaphenazole for the treatment of pressure injuries.
PI: David Granville. Co-investigator: Chris Turner.
Pressure injuries, also called pressure ulcers or bed sores, are wounds or injuries to the skin and underlying tissue that can range from reddening to severe damage to the muscle, tendon, and bone. Pressure injuries result from a combination of prolonged pressure, friction, shear forces, and moisture on the skin and are linked to fatal septic infections. Pressure injuries are alarmingly common among people with spinal cord injuries with 40% of this population experiencing at least one pressure injury in their lifetime. There is an urgent need to develop new strategies for pressure injuries as with current treatment options, pressure injury wounds can stay open and reoccur for years. Our research team has recently discovered that a safe antibiotic called sulfaphenazole, which has already been approved for use in patients, can significantly improve the healing of pressure injuries in an experimental model. Sulfaphenazole treatment was able to decrease the severity of the injuries, decrease wound area, and decrease inflammation. In this proposal, our objectives are: 1) to further characterize the actions of sulfaphenazole in pressure injuries and 2) to develop a new formulation of sulfaphenazole that would be optimized and ready for administration to patients in the clinic. Funding for our study will advance our goal to develop sulfaphenazole into a novel, effective therapy for people afflicted by pressure injuries.
Characterising autoantibodies in human traumatic spinal cord injury.
PI: Veronica Hirsh Reinshagen. Co-investigators: Brian Kwon, Michael Nimmo.
Antibodies are special proteins that develop when the body mounts its defense against an injury or attack like an infection. Sometimes ‘auto’ antibodies develop that mistakenly target and react with a person’s own tissues or organs, causing tissue damage and requiring treatment with strong anti-inflammatory drugs. Autoantibodies against brain, spinal cord and other tissue components have been found in people with traumatic spinal cord injury (tSCI) using blood analysis techniques that are only available for research use. We do not yet know if these autoantibodies in people with tSCI cause additional damage, are harmless or even protective. This project will use a method that is routinely used in clinical laboratories to see if we can detect autoantibodies in the blood of patients with tSCI shortly after injury. This test will also allow us to determine if different patients have the same or different autoantibodies, which is currently unknown. If, as we suspect, autoantibodies are indeed found in the blood of people with tSCI, future projects using the same clinical tests will determine how long these autoantibodies are present, as well as if and how they influence the clinical and radiological evolution of tSCI. Providing clinicians with additional tools to guide the choice of treatment for individual patients will eventually lead to improved recovery after tSCI. Because we will be using a clinical test, our findings can be quickly implemented in the clinic.
Improving clinical trials by understanding placebo effects in chronic spinal cord injury: A pilot study.
PI: John Kramer. Co-investigator: Mike Berger
The goal of the proposed study is to understand how the expectation for a benefit changes common outcome measures in individuals with spinal cord injury (SCI). In clinical trials, this effect is usually accounted for with the inclusion of a “placebo control”. For practical and ethical reasons, placebos for many SCI clinical trials are a major challenge to include. For example, if an intervention involves a surgical procedure, it may be unethical and too costly to have a placebo condition. Because of this, it is difficult to say whether an intervention is caused by “real” changes in the physiology and anatomy of SCI or if a given change is merely related to the expectation for a benefit (that is, placebo effects). As a partial solution, we propose to examine placebo effects in individuals with chronic SCI. This will involve the design of a study in which subjects are instructed they will be administered placebo or caffeine, but, in reality, only ever receive placebo. Based on previous studies and our own experience, the belief that caffeine has been ingested will be sufficient to create the expectation for a benefit. This expectation will, in turn, improve performance on some tests (e.g., walking). At the conclusion of our project, we will have generated preliminary results as to the magnitude of placebo effects, which will inform a larger, more substantive proposals to other funding agencies.
Advanced MRI techniques to measure spinal cord microstructure in vivo: development, reproducibility and application to SCI. ($18,000)
PI: Cornelia Laule. Co-investigators: Brian Kwon, Piotr Kozlowski, Wayne Moore, Veronica Hirsch-Reinshagen, Manraj Heran, Eric Sayre, Sarah Morris, Andrew Yung.
When someone has a spinal cord injury (SCI), magnetic resonance imaging (MRI) can take pictures of the spinal cord damage. One limitation of ‘standard’ MRI is that changes in picture contrast are not specific to the type of damage – loss of tissue and extra water from inflammation look the same. Also, areas which appear normal might have damage that standard MRI cannot detect. Knowing what specific kind of damage has occurred would help inform SCI prognosis and treatment decisions, and new therapies could be tested using objective markers of tissue health. More sophisticated MRI methods can reveal the type of damage that happens in SCI. Our previous research comparing MRI and microscope images in human SCI post-mortem tissue identified MRI techniques specific for myelin and axons, the main components of neurons which get damaged in SCI. Our current research will translate these tissue-specific MRI methods into scanning living people. We will test the advanced MRI techniques on controls and people living with SCI. We will test how well our advanced MRI scans work in people with implanted metal screws and rods, which are common in the SCI population and can distort MRI scans. Data will be collected twice from each volunteer to see how reproducible the results are. Determining how well advanced MRI can measure spinal cord damage in living people is an important next step in moving these more specific MRI methods towards every day clinical use, and for testing new treatments.
Development of a pandemic toolkit for individuals with a spinal cord injury based on an evaluation of current resources.
PI: Ben Mortenson. Co-investigators: Jaimie Borisoff, Julia Schmidt, Chris McBride.
COVID-19 is causing changes and challenges for everyone. Guidelines include wearing masks and regularly washing hands. Current rules also mean people have to stay physically distanced. This effects normal activities and can lead to increased social isolation and loneliness. People with SCI may be especially at risk, as it may affect their routine, services, and health. A few organizations have made resources for people in North America with SCI; but their usability and relevance for people with SCI have not been tested. We will provide participants with these resources. We will then interview them to get their feedback about them. We hope to use their thoughts to revise these resources for people with SCI and add any needed content. This COVID-19 toolkit will provide information, advice, and recommendations to improve quality of life. It will also be useful for any future pandemics.
