Molecular Markers of Neuroplasticity During Exercise in People With Incomplete Spinal Cord Injury

Inclusion Criteria:

• Must be motor incomplete spinal cord injury (ASIA C or D) of 1 year or greater duration, with anatomical lesions between C1-T10
• Must be between 18 and 75 years of age
• Must be ambulatory with passive range of motion consistent with normal walking, and must include: ankle dorsiflexion ankle to 10° and plantarflexion to 30°, knee flexion from 0 to 90°, hip flexion/extension to 90° to -10°.
• Must be medically stable with medical clearance to participate, with absence of concurrent severe medical illness including: unhealed decubiti, existing infection, significant cardiovascular or metabolic disease which limits exercise participation, significant osteoporosis (as indicated by history of fractures following injury), active heterotrophic ossification in the lower extremities, known history of peripheral nerve injury in lower legs, history of known traumatic head injury, mental illness, history of pre-existing QT interval prolongation, congenital long QT syndrome, and history of pulmonary complications, including significant obstructive and/or restrictive lung diseases
• May be undergoing concurrent physical therapy
• May be of childbearing potential (for women)
• Men and women will be recruited for participation in the proposed study at rates consistent with national and local average of gender disparities of SCI (80% male, 20% women)
• Individuals of different ethnicities will be recruited at rates similar to the national and local ethnicity rates. Current data since 2005 indicate that of the entire population of SCI, 66.1% are Caucasian, 27.1% are African American, 6.6% are of Hispanic origin, and 2.0% are Asian.

Exclusion Criteria:

• Weighing more than 300lbs
• Ventilator-dependency
• Use of substantial orthopedic bracing to stabilize the cervical or thoracic vertebral column
• Inability to tolerate 10 minutes of standing without orthostasis (decrease in blood pressure by 20 mmHg systolic and 10 mmHg diastolic).
• Women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the pharmacological agents on the developing fetus
• Exhibiting symptoms suggestive of depression according to the Personal health Questionaire (PHQ-9)
• Subjects who exhibit hemoglobin levels consistent with anemia (<13g/dL for men and <12g/dL for women) will be excluded from the study.
• Currently taking prescribed anti-depressant medications, including specific monoaminergic agents, their precursors or their agonists, antipsychotics, medications known to prolong the QT interval, or other medications with known interactions to the SSRIs. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 14-day washout period for SSRIs and a 72 hour washout for Tizanidine will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
• Currently taking prescribed anti-spastic medications. Specific agents to be excluded include baclofen (Lioresal®) and benzodiazepines (Diazepam®). Selected agents used for pain modulation will be evaluated per subject to ascertain potential interactions with test agent. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 72-hour minimum washout period for all such medications will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
• Clinically diagnosed liver, renal, or other metabolic disease that may interfere with drug action and/or clearance