Introduction and overview
The mission of the North American Clinical Trials Network® (NACTN) is to bring promising therapies out of the laboratory and into clinical trials in a manner that provides strong evidence of effectiveness and safety.
NACTN supports a network of 11 clinical centers as well as clinical coordinating, data management and pharmacology sites, all dedicated to establishing best practices in the care and treatment of spinal cord injury (SCI).
By uniting experts across the country, NACTN conducts clinical trials that maximizes patient safety while gathering valid, meaningful data to speed the delivery of new therapies to the community.
In addition to translating discoveries from the lab into clinical studies, NACTN maintains a patient registry of information that is important to the design and testing of possible new treatments for SCI. Currently, the network has enrolled over 800 acutely injured patients into the registry.
Information collected includes the following:
- Medical history
- Initial clinical status
- Type of neurological and bony injury
- Surgical therapy
- Adverse events (cardiac, pulmonary, hematological, infectious, skin, etc.)
- Magnetic resonance imaging (MRI)
The purpose of the NACTN SCI Registry is threefold:
- Establish the natural course of recovery following a spinal cord injury using standardized and validated acute-care and follow-up data.
- Facilitate scholarly research and publications.
- Serve as a comparison group in spinal cord clinical trials and help establish protocols.
NACTN has shared its Registry data with academic institutions and investigators to facilitate research and publications, and serve as a comparison group in other SCI clinical trials.
Creating smarter tools for measuring treatment outcomes
The Reeve Foundation's Neurological Outcomes Assessments (NOA) task force, an integral part of NACTN, was assembled to develop more sensitive outcome measures for use in clinical trials of spinal cord injury.
The NOA task force, representing experts from Europe, Canada and the United States, is currently working to develop new and advanced tools to measure treatment outcomes.
As a comparison, the ASIA Impairment Scale (American Spinal Injury Association), is the most common outcome assessment tool for paralysis. However, this test is not sensitive enough to capture small, incremental changes in individuals with spinal cord injury.
"Manual muscle testing in the AIS likely won't detect small changes that occur after a therapy," said Susan Harkema, Ph.D., University of Louisville and co-chair of the NOA task force. "The worst thing that could happen is that an intervention could be successful and not show up on the measurement scales we have now."
NOA will go beyond the existing assessment tools to evaluate and detect incremental improvements across a variety of outcome areas (motor, autonomic, sensory and pain). With a more sophisticated and sensitive approach to measuring the impact of interventions, we believe new treatments will emerge to address the myriad complications of a spinal cord injury.
Global collaboration to expedite therapies
NACTN has been supported by the Department of Defense (DOD) since its inception in 2005. The NACTN mission aligns with DOD’s priority research area to identify and develop medical techniques for early intervention in life-threatening battle injuries.
Currently, NACTN is collaborating with similar networks around the world to define the natural history of spinal cord injury and develop new approaches and tools to measure the success of treatments.
Our hope is that these connections will provide the foundation for a global network that will accelerate the development of safe and effective treatments, offering new solutions to the millions living with spinal cord injury worldwide.
NACTN also works closely with the Reeve Foundation International Research Consortium on Spinal Cord Injury to foster an ongoing dialogue between researchers and clinicians. Through workshops and other scientific meetings, Consortium members have the opportunity to connect directly with NACTN medical professionals, facilitating educational exchanges about emerging treatments for spinal cord injury.
Current priorities and clinical trials
NACTN researchers have developed a rigorous process to review potential therapies and reach consensus about which should move into clinical trials. This includes the ongoing work to evaluate the impact of riluzole on acute injuries.
NACTN conducted a Phase I safety study of the neuroprotective drug riluzole, which assessed the safety of the drug in 36 patients with acute spinal cord injury. The results were published in the Journal of Neurotrauma.
Based on the promising results of this trial, NACTN has partnered with AOSpine North America (AOSNA) to move forward with a Phase II/III clinical trial called RISCIS (Riluzole in Spinal Cord Injury Study). RISCIS will further evaluate the safety of riluzole and see if the drug works to improve recovery following a spinal cord injury compared to a placebo.
Riluzole is thought to work by blocking sodium channels, which in turn prevents the stimulation of glutamate receptors. Excess glutamate can be toxic to nerves. The drug is already approved for treating ALS, and shows promise as an early-phase treatment in spinal cord injury.
Beyond riluzole, there is a robust pipeline of potential treatments for spinal cord injury that are entering clinical trials. We strongly encourage all community members to review the Reeve Foundation’s recommended resources prior to volunteering for any study.
As data provides the key to better understand spinal cord injury, NACTN will also continue to enroll acutely injured patients into the data registry and share findings with the spinal cord field at large.