Serotonergic Modulation of Motor Function in Subacute and Chronic SCI

Status unconfirmed · Phase 1 · Has a placebo group

Conditions studied: Spinal Cord Injury

In brief

The manifestation of weakness and involuntary reflexes following motor incomplete spinal cord injury (SCI) may be partly a result of damage to descending pathways to the spinal cord that release serotonin. In models of SCI, for example, application of agents that simulate serotonin has been shown to modulate voluntary motor behaviors, including augmentation of walking recovery. In humans following neurological injury, the effects of 5HT agents are unclear. Few previous reports indicate improved motor function following administration of agents which enhance the available serotonin in the brain, although some data suggests that decreased serotonin may be beneficial. In this application, the investigators propose to study the effects of clinically used agents that increase or decrease intrinsic serotonin activity in the brain on strength and walking ability following human motor incomplete SCI. Using detailed electrophysiological recordings, and biomechanical and behavioral measures, the investigators will determine the effects of acute or chronic doses of these drugs on voluntary and involuntary motor behaviors during static and dynamic conditions. The novelty of this proposed research is the expectation that agents that enhance serotonin activity may increase abnormal reflexes in SCI, but simultaneously facilitate motor and walking recovery. Despite potential improvements in voluntary function, the use of pharmacological agents that may enhance spastic motor behaviors following SCI is in marked contrast to the way in which drugs are typically used in the clinical setting.

Key facts

Study ID

NCT01788969

Run by

Shirley Ryan AbilityLab

People needed

42

Starts

2005-06-01

Expected to finish

2019-12-01

Last updated by the study team

2019-04-22

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• age of subjects between 18 and 65 years of age, due to the effects of greater age on functional recovery of ambulation (Penrod et al. 1990);
• medically stable with medical clearance from the subject's primary internist or physiatrist to participate;
• level of the lesion between C5-T10 spinal cord level due to non-progressive etiology;
• <6 months or >1 yr since initial injury. Range of motion requirements include: ankle dorsiflexion ankle to 10 degrees and plantarflexion to 30 degrees, knee flexion from 0 to 120 degrees, hip flexion to 90 degrees, and hip extension to 10 degrees.

You may not qualify if…

• presence of concurrent severe medical illness, including unhealed decubiti, existing infection, cardiovascular disease, 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
• a history of cardiovascular or pulmonary complications, including significant obstructive and/or restrictive lung diseases
• inability to tolerate 30 minutes of standing without orthostasis (decrease in blood pressure by 20 mmHg systolic and 10 mmHg diastolic)
• individuals who are undergoing concurrent physical therapy will be excluded to eliminate confounding effects
• women of childbearing potential will not be excluded, although women who are pregnant will be excluded due to the lack of proven safety of pharmacological agents in pregnant women
• cranial stimulation exclusions: history of epilepsy or a seizure event, metal implants in the head or face, unexplained and recurring headaches, skull abnormalities or fractures, implanted cardiac pacemaker or suffered a concussion within the last 6 months
• interactions with other medications or previous sensitivity to SSRIs, 5-HT antagonists or anti-histamines
• patients prescribed medications for alleviation of spastic motor behaviors, anti-depressant medications, or other medications with known interactions to SSRIs 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 minimum washout period for all such medications will be utilized
• patients with known liver, renal, or other metabolic disease that may interfere with drug action and/or clearance will be excluded from the proposed study. The low daily dosage of the agent to be used (10 mg Lexapro and 16 mg Cypro) has shown very little side effects with patients with hepatic or renal disease
• patients who are diagnosed or previously diagnosed with depression will be excluded. A preliminary screening tool (Center for Epidemiological Studies - Depression Scale) will be administered to all patients. Scores > 16 indicate symptoms of depression. For those patients, a physician will be required to evaluate the subject to determine eligibility.

Where it is running

• Rehabilitation Institute of Chicago — Chicago, Illinois, United States

Full record on ClinicalTrials.gov

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