Serotonergic Modulation of Motor Function in Subacute and Chronic SCI

NCT01788969 | Unknown Phase 1

• 1 other identifier: STU00014259
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Cord Injury

Keywords

Gait training; Lexapro; Tizanidine

Outcome Measures

Primary Outcomes (1)

• Walking Index for Spinal Cord Injury (WISCI II)

  Evaluation of bracing, assistive device, and assistance required for ambulation

  Compare changes in WISCI II pre to post training with placebo to pre to post training with Lexapro during a 10-12 week time period.

Secondary Outcomes (8)

• Volitional Strength

  Pre Training (Day 1), Pre Drug B (approx end of week 5), Post Final (approx end of week 10)

• Gait kinematics

  Pre Training (Day 1), Pre Drug A (approx end of week 2), Post Drug A (approx end of week 4), Pre Drug B (approx end of week 5), Post Drug B (approx end of week 9), Post-Final (approx end of week 10)

• Fastest possible walking velocity over ground (FV; m/s)

  Pre Training (Day 1), Pre Drug A (approx end of week 2), Post Drug A (approx end of week 4), Pre Drug B (approx end of week 5), Post Drug B (approx end of week 9), Post-Final (approx end of week 10)

• Six minute walking distance (m)

  Pre Training (Day 1), Pre Drug A (approx end of week 2), Post Drug A (approx end of week 4), Pre Drug B (approx end of week 5), Post Drug B (approx end of week 9), Post-Final (approx end of week 10)

• Lower Extremity Motor Scores (LEMS)

  Pre Training (Day 1), Pre Drug A (approx end of week 2), Post Drug A (approx end of week 4), Pre Drug B (approx end of week 5), Post Drug B (approx end of week 9), Post-Final (approx end of week 10)

Study Arms (2)

Gait Training with Lexapro

EXPERIMENTAL

Gait training 2 weeks, gait training 4 weeks (3 X week) with Lexapro (10mg SSRI), wash out period of 1 week, gait training, for 4 weeks with placebo (10 mg). Patients will also be provided prescribed TIZ by their physician to help control of spastic motor behaviors.

Drug: Lexapro

Gait Training with Placebo

ACTIVE COMPARATOR

Gait training 2 weeks, gait training for 4 weeks (3X week) with Placebo (10 mg), wash out period of 1 week, gait training for 4 weeks with Lexapro(10 mg). Patients will also be provided prescribed TIZ by their physician to help control of spastic motor behaviors.

Drug: Placebo

Interventions

Lexapro DRUG

Agent + training vs Placebo + training

Also known as: escitalopram

Gait Training with Lexapro

Placebo DRUG

Agent + training vs Placebo + training

Also known as: microcrystalline dextrose

Gait Training with Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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
• 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.

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead

Study Sites (1)

Rehabilitation Institute of Chicago

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Escitalopram

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Thomas G Hornby, PhD, PT

  Rehabiltiation Institute of Chicago/UIC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: February 7, 2013
• First Posted: February 11, 2013
• Study Start: June 1, 2005
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2019
• Last Updated: April 22, 2019

Record last verified: 2019-04

Locations

US (1)