Clinical phase I trial based on hypothermia


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Hypothermia is a condition in which the body temperature drops below the required temperature for normal metabolism and body functions. Therapeutic hypothermia, in which the lowering of the body temperature is done in a clinically controlled environment, could have a functional benefit. The initial damage induced by spinal cord injury is quickly followed by a so-called secondary injury that extends even further and will result in a worse functional outcome. Neuroprotection aims at limiting this extension and numerous experimental results show that hypothermia could be a successful neuroprotective therapy. Although the mechanisms of action of hypothermia have not been described yet many believe that it mitigates secondary injury mechanisms within the CNS such as excitotoxicity, blood-brain barrier breakdown, free radical production and inflammation.

Previous attempts on human subjects were done on conditions like traumatic brain injury and allowed to conclude that the best treatment would be a modest hypothermia with a body temperature of 32-34°C at least 48 hours.

 


Based on these results the Miami Project to Cure Paralysis started a phase 1 clinical trial aiming at testing the effect of hypothermia on spinal cord injury individuals. Thirty-five acute cervical SCI patients had a cooling catheter placed in a large blood vessel (vena cava) in order to cool their body a few degrees to 33 degrees Celsius. In order to be beneficial, the cooling was started within 9 hours post-injury, on average, and was maintained for 48 hours (see figure). After which, participants were slowly re-warmed at one degree every eight hours, proceeded with standard medical care and followed up to one year after the injury.

The final analysis revealed that mild hypothermia did not cause any particular complication. Although the number of the treated subjects was too small to draw any valid conclusion on efficacy there seemed to be a "trend" to a better recovery one year after injury than what would normally occur spontaneously.

Based on this initial success a Phase II/III clinical trial is currently being planned to evaluate the safety of different durations of hypothermia, initiated within 6 hours post-injury, and then confirm the efficacy of the best duration. This trial will be named ARCTIC, the acronym for Acute Rapid Cooling Therapy for Injuries of the Spinal Cord. More than 200 subjects will be enrolled and funding has yet to be approved by the American National Institutes of Health, but if successful ARCTIC could change the standard of care for spinal cord injury medicine worldwide.

Reference:
Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Dididze M, Green BA, Dalton Dietrich W, Vanni S, Wang MY, Levi AD. Spinal Cord. 2012 Dec 18.