Protocol for Rapid Onset of Mobilization in Patients With Traumatic Spinal Cord Injury II (PROMPT-SCI II) Trial

Protocol for Rapid Onset of Mobilization in Patients With Traumatic Spinal Cord Injury II (PROMPT-SCI II) Trial: Initiating Early Acute Cycling Within the First Days After Spinal Cord Injury to Decrease Complications and Improve Neurofunctional Recovery

Spinal cord injuries (SCI) are among the most catastrophic survivable events experienced by human beings. Affected individuals remain with lifelong neurological impairment involving motor, sensory, bladder and bowel functions, which in turn impacts quality of life and independence. Currently, patients have no access to exercise therapy for weeks to months after the injury because clinicians remain fearful that early initiation of exercise therapy may be harmful to patients, and could lead to neurological deterioration. Patients are therefore mostly immobilized during the first weeks after the injury, and are at high risk of complications associated with immobility. In addition, there are compelling preclinical evidence showing that early exercise therapy is effective for promoting neurofunctional recovery. The PROMPT-SCI trial was the first to initiate early exercise therapy in the form of in-bed leg cycling within days after SCI. This trial has shown that it is safe and does not lead to neurological deterioration. However, in-bed leg cycling remains difficult to translate into the clinical environment of acute SCI, and its potential to decrease complications and improve neurofunctional recovery seems limited by the positioning in bed. The PROMPT-SCI II trial will therefore evaluate the potential of sitting leg cycling initiated within the first week of a SCI to decrease complications and improve neurofunctional recovery up to one year after the injury, in comparison to our prior data obtained with early in-bed cycling.

BACKGROUND: A severe traumatic spinal cord injury (SCI) leads to permanent sensorimotor neurological deficits. During acute care, patients are mostly immobilized due to pain (from injuries and surgeries) and inherent paralysis from the SCI, resulting in complications such as pneumonia, pressure injuries, deconditioning, etc. There is also compelling preclinical evidence showing that early immobilization after SCI impairs the capacity of the nervous system to reorganize and promote neurological recovery. The PROMPT-SCI trial was the first to perform a clinical trial of early acute exercise therapy in the form of in-bed leg cycling starting within 5 days of a SCI, leading to these findings: 1) no adverse events associated with cycling, 2) decreased rates of complications, and 3) activation of paralyzed muscles triggered by cycling. Unfortunately, the PROMPT-SCI trial failed to demonstrate neurofunctional benefits similar to those observed in preclinical studies, potentially due to the short 2-week duration of the intervention, and to insufficient tactile and proprioceptive feedback in lower extremities with in-bed cycling, which could be circumvented by performing seated cycling throughout the entire acute care.

GOALS: This longitudinal cohort study will investigate the feasibility and clinical benefits of early acute seated cycling on neurofunctional recovery and complications. The hypotheses are:

H1: There will be no serious adverse events; 80% of participants will complete a first session within 5 days of the SCI and at least 80% of all planned sessions thereafter.

H2: Complication rates will be decreased for pneumonia, urinary tract infection and pressure injuries.

H3: Neurofunctional recovery will be improved 1 year after the SCI.

The specific aims are:

Aim 1: Assess the feasibility of performing early seated cycling throughout acute care.

Aim 2: Assess the complication rates and neurofunctional recovery up to 1 year post-SCI.

METHODS: For this 5-year study, 102 participants with severe acute traumatic SCI (paralyzed lower extremities without anti-gravity strength) will be recruited. Participants will perform daily 30-minute sessions of seated cycling throughout acute care, starting as soon as they are fit for cycling. Adherence to protocol, complications and neurofunctional recovery (motor/sensory recovery, functional independence, spasticity) will be assessed up to 1 year post-SCI. Neurophysiological and biomechanical responses to cycling will be assessed from electromyographic and plantar pressure measurements. Outcomes will be compared to our control cohort of patients with severe SCI who have not received exercise therapy. The association between neurophysiological/biomechanical responses and outcomes will be assessed.

Inclusion Criteria:

• adults 18 years or older with non-penetrating traumatic SCI
• SCI severity AIS grade A (complete injury with no motor or sensory function below lesion), B (sensory but no motor function preserved) or C (motor function preserved with most key muscles unable to move against gravity)
• NLI between C0 and L2; and spine surgery performed within 48 hours of SCI

Exclusion Criteria:

• intubated and mechanically ventilated
• conditions interfering with patient safety or ability to undergo cycling
• body mass index 40 kg/m2 or less (to prevent "frog leg" position during cycling)
• moderate or severe traumatic brain injury
• hemodynamic instability
• pelvic or lower extremity
• injury with weight-bearing or mobilization restrictions