Department of Defense gives $5.4 million to spinal cord injury research

The Reeve Foundation's North American Clinical Trials Network (NACTN) consented the first patient into its Riluzole acute injury Phase I safety study on April 12, 2010. On June 20, 2011, the 36th subject was recruited and enrollment was complete. The Principal Investigators used 15 data collection forms to track the clinical course and outcomes (safety and complications) of these subjects, starting at the time of injury and their consent to enter the trial. The data protocol records detailed patient information and outcomes during acute care through hospital discharge, and scheduled follow-up visits at six-weeks, three-months and six-months post-injury. The last patients will have their six-month follow-up visits in December.

NACTN investigators and the Data Management Center at the University of Texas School of Public Health, Houston, have begun to analyze the data and develop the protocol for a Phase ii b randomized efficacy study.

Riluzole is a neuroprotective drug presently used in the treatment of amyotrophic lateral sclerosis where it prolongs the life spans of patients. It acts by blocking the ability of sodium and calcium ions to enter and damage neurons and glia. Laboratory studies have shown it to be effective in limiting traumatic damage to the spinal cord.

Background information previously posted about the Riluzole trial
The Phase I study will evaluate safety of riluzole in acutely injured spinal cord patients; it will also investigate its pharmacodynamics (biochemical and physiological effects) and pharmacokinetics (what the body does to it). The trial will also collect information about its efficacy as measured by ASIA (motor and sensory outcomes), ASIA Impairment Grade and Brief Pain Inventory.

The riluzole protocol is unique in several ways: (1) the detail with which possible adverse effects of the therapy will be studied and (2) the use of pharmacokinetic and pharmacodynamic data and its correlation with adverse effects and efficacy. Previous studies of drug therapies for SCI have not measured blood and cerebrospinal fluid levels to see if effective or toxic levels of the drug were reaching the spinal cord and brain.

This Phase I is a multi-site, single arm, active treatment pilot study involving 36 subjects. Presently, 5 NACTN sites can enroll patients; the other 3 clinical sites are in the process of fulfilling their final regulatory requirements. If the rate of adverse effects in the initial trial group is not greater than that expected in comparison with the NACTN data registry, a Phase II study of a larger number of patients will be undertaken as an efficacy trial.

To participate in the study patients must:  

• be between 18 and 70 years of age
• be willing to give written informed consent
• have no other life-threatening injury
• have a spinal cord injury at the neurologic level from C4 to T12
• have an ASIA Impairment Scale level A, B or C
• be able to receive Riluzole within 12 hours post-injury.

As with all clinical trials, there are exclusion criteria that apply. These include pregnancy or breast-feeding, substance abuse, a penetrating spinal cord injury or hypersensitivity to rilzuole or any of its components.

Download the new NACTN brochure.

A support system for clinical trials: accelerate and validate

When therapies are ready for human trials, where do they go?

The North American Clinical Trials Network (NACTN) is one more way that the Reeve Foundation is moving promising therapies from the lab to spinal cord injured patients. NACTN is working hard to insure that any clinical trial will be done in a way that maximizes both patient safety and our ability to gather valid, meaningful data.

NACTN is an international network of hospitals with highly trained personnel and uniform protocols and data collection that help to ensure safety for all trial subjects and interpretable trial data. NACTN is:

• Gathering and documenting patient medical information in a data registry to better understand the body’s natural course of recovery after injury. This information will allow us to more accurately identify improvement that results from the therapy being tested
• Using standardized patient assessment protocols and developing new ones
• Primed to conduct new trials of therapy for spinal cord injury

Expediting effective trials

Now, when researchers get the go-ahead for human trials, they don’t have to build the support system for such studies from the ground up – NACTN has already built the standing infrastructure.

Casting the widest net possible

Our immediate future plans include expanding NACTN to new clinical centers. We have begun a Neurological Outcomes Assessment initiative to develop new, more sensitive measures of function for spinal cord injury, and we are working with similar clinical networks in Europe and Canada to accomplish this goal. We also received a multi-million dollar grant from the U.S. Department of Defense to expand these important efforts to military, Veterans Administration, and select civilian hospitals.

NACTN Mission

The NACTN Data Registry

NACTN Sites

NACTN Resources

NACTN Mission

The mission of the North American Clinical Trials Network for the Treatment of Spinal Cord Injury is to bring promising therapies out of the laboratory and into clinical trials, in a manner that provides incontrovertible evidence of effectiveness and safety. The North American group is collaborating with a similar network in Europe, and one  just now forming in Canada, to define the natural history of spinal cord injury and develop measures for assessing treatment success. It is hoped that these collaborations will provide the foundation for a global network that will speed therapeutic development and ensure that powerful new therapies will be made available to those in need.

NACTN will also work closely with the Reeve Foundation Individual Research Consortium on Spinal Cord Injury to ensure an ongoing dialogue between laboratory researchers and clinicians. Through workshops and other educational programs, Consortium scientists will have the opportunity to network with clinical specialists from across North America and Europe, facilitating educational exchanges and iterative discussions about the development of effective treatments for spinal cord injury.

The NACTN Data Registry

The Registry serves two vital purposes. The first is to provide a statistical and scientific platform to develop the data, logistics and collaborations necessary to conduct Phase I and Phase II clinical trials of potential therapies. The second is to develop high quality, standardized and validated acute care and follow-up data on a representative national sample of male and female adult patients who have suffered a spinal cord injury with neurological deficits. This acute care and follow-up data are an invaluable and unique resource needed to characterize the trajectory (natural history) of individuals who have suffered a spinal cord injury.

All data are collected prospectively starting at the time of admission to a NACTN clinical center. The registry data includes extensive demographic information, past medical history, pre-injury medication use, circumstances of injury, time of injury, and the time of arrival to the treating NACTN hospital. Further detail is elicited about the condition of the patient on arrival and includes a clinical evaluation, measurement of state of consciousness with the Glasgow Coma Scale (GCS) and of associated injuries with the Abbreviated Injury Scale. The American Spinal Injury Association impairment scale (AIS) is scored on admission and at key times throughout the patients’ hospital and post-hospital course. All examiners received training on performing the AIS examination and study procedures. Data are also collected on radiographic findings, non-operative and operative treatments, timing of treatments, and perioperative complications. Discharge AIS score, and the type of facility to which the patient is transferred are recorded in the discharge form. After acute care discharge, long-term follow-up is scheduled at approximate intervals of six and twelve months after discharge. The follow-up registry protocol includes: the AIS Impairment Scale, and where appropriate, the Functional Independence Measure FIM™, the Spinal Cord Independence Measure (SCIM), and the Walking Index for Spinal Cord Injury (WISCI) evaluations.

Currently there are nine clinical centers participating in the NACTN SCI Registry. As of Jul 18, 2011, a total of 488 patients had been enrolled into the Registry. These case numbers are sufficiently large now to have adequate statistical precision for detailed study of acute care complications and their relationship to short-term and long-term outcomes.

The Registry and NACTN expertise are now recognized as resources for the SCI field at large. Recently for example, the NACTN data protocol and Information about the structure and logistics of the Registry were sent to investigators at Monash University, Melbourne, Australia for inclusion in a world-wide survey of Spinal Cord Registries. NACTN data are being shared and exchanged with other SCI clinical networks, including STASCIS (the Surgical Treatment of Acute Spinal Cord Injury database, University of Toronto); EM-SCI (the European Multicenter Study about Spinal Cord Injury registry [18 European clinical sites], University of Zurich Balgrist Hospital); and the Reeve NeuroRecovery Network (University of Louisville).

NACTN Sites

At the present time, the Reeve Foundation North American Clinical Trials Network is based at nine clincial centers in the U.S. and Canada. The tenth center is responsible for data analysis and management.

NACTN Coordinating Center
The Methodist Hospital
Principal Investigator:
Robert G. Grossman, M.D.

Data Management Center and Statistical Coordinating Center
University of Texas School of Public Health, Houston, TX
Principal Investigator:
Ralph Frankowski, Ph.D.

Pharmacology Center
University of Houston, Houston, TX
Principal Investigator:
Diana Chow, Ph.D.

Clinical Sites:

Brooke Army Medical Center (BAMC)
San Antonio, TX
Principal Investigator
Robert Marsh, MAJ, MD, PhD

Thomas Jefferson University, Philadelphia, PA
Principal Investigator:
James Harrop, M.D.

University of Louisville, Louisville, KY
Principal Investigators:
Susan Harkema, Ph.D.
Maxwell Boayke, M.D.

University of Maryland Medical System, Baltimore, M.D.
Principal Investigator:
Bizhan Aarabi, M.D.

University of Miami, Miami, FL
Principal Investigator:
James Guest, M.D.

University of Texas Health Science Center, Houston, TX
Principal Investigator:
Michele Johnson, M.D.

University of Toronto, Toronto, ON
Principal Investigators:
Charles Tator, M.D.
Michael G. Fehlings, M.D., Ph.D.

University of Virginia, Charlottesville, VA
Principal Investigator:
Christopher Shaffrey, M.D.

Walter Reed National Military Medical Center Bethesda (the merged Army/Navy/Air Force facility), Washington, DC
Principal Investigator:
Michael K. Rosner, M.D., LTC, MC, USA

With spinal cord clinical trials already underway in the U.S. and many more to come in the next few years, there is an urgent need to build bridges among researchers and pave the way for accelerated progress. These websites provide up-to-date information on current trials, discussion-based workshops, and other initiatives that seek to define guidelines and standards.

- Search for a Clinical Trial

The Christopher and Dana Reeve Foundation was one of the founding members of the International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP). We, along with our ICCP colleagues, believe the ICCP Guide for Experimental Treatments for Spinal Cord Injury
is a crucial resource for people living with spinal cord injury, their families and their caregivers.

In today's wired world, there is a wealth of information available about treatments, proven and unproven, for the paralysis and other dysfunctions that result from a traumatic injury to the spinal cord and it is oftentimes challenging to separate the wheat from the chaff.  The Reeve Foundation hopes that readers of these guidelines will be empowered to think critically about potential therapies for spinal cord injury and pose the important questions that should be asked.

Resource information on stem cell therapy
- ICCP Guide for Experimental Treatments for Spinal Cord Injury
- Guidelines: Clinical Translation of Stem Cells (International Society for Stem Cell Research)
- Patient Handbook on Stem Cell Therapies from the ISSCR

Report of the International Clinical Trials Workshop on Spinal Cord Injury: click here to download the PDF or view the report in your browser
This paper discusses information presented at the International Clinical Trials Workshop on Spinal Cord Injury, held in Vancouver, Canada in February 2004. 
Reprinted by permission from Spinal Cord (citation below), copyright 2004, Macmillan Publishers Ltd.
Report of International Clinical Trials Workshop on Spinal Cord Injury February 20-21, 2004, Vancouver, Canada, Spinal Cord 2004;42(10):591-597.

ClinicalTrials.gov: http://clinicaltrials.gov/ct/gui/c/b
Search for federally and privately supported clinical trials.

NIH Roadmap: http://nihroadmap.nih.gov
Learn about the National Institutes of Health's "roadmap" for research in the 21st century. The site identifies major opportunities and gaps in biomedical research.

NINDS Workshop: Translating Promising Strategies for Spinal Cord Injury Therapy: http://www.ninds.nih.gov/news_and_events/proceedings/sci_translation_workshop.htm
Read about this discussion-based workshop that took place in 2003 that brought together leaders of major North American research groups that focus on SCI research.

Download the new NACTN brochure.