Overview

This trial is active, not recruiting.

Condition spinal cord injury
Treatments lexapro, placebo
Phase phase 1
Sponsor Rehabilitation Institute of Chicago
Start date February 2012
End date July 2017
Trial size 88 participants
Trial identifier NCT01753882, STU00056589

Summary

The primary goal of the proposed clinical trial is to investigate the combined effects of walking training and monoaminergic agents (SSRIs and TIZ) on motor function of individuals in sub-acute (2-7 mo) human motor incomplete Spinal Cord Injury (SCI), with a primary emphasis on improvement in locomotor capability. We hypothesize that the use of these drugs applied early following SCI may facilitate independent stepping ability, and its combination with intensive stepping training will result in improved locomotor recovery following incomplete SCI. Loss of descending control via norepinephrine inputs following spinal cord injury can impair normal sensorimotor function through depressing motor excitability and impairing walking capacity. Replacing these inputs with drugs can alter the excitability and assist with reorganization of locomotor circuits. Assessment of single-dose administration of these agents has been tested in patients with motor incomplete spinal cord injury; only limited changes in walking performance have been noted. The resultant onset of weakness and increase in involuntary reflexes following motor incomplete SCI may partly be a result of damage to descending pathways to the spinal cord that control the release of serotonin. In models of SCI, for example, application of agents that simulate serotonin has been shown to change voluntary motor behaviors, including improvement 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 increased serotonin may be beneficial. In this application, we 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, we will determine the effects of single or chronic doses of these drugs on voluntary and involuntary motor behaviors during clinical measures and walking measures. The novelty of this proposed research is the expectation that agents that increase serotonin activity may increase abnormal reflexes in SCI, but simultaneously help to 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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Gait training 2 weeks, gait training for 4 weeks (3X week) with Lexapro (10 mg 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.
lexapro escitalopram
Agent + training vs Placebo + training
(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.
placebo microcrystalline dextrose
Agent + training vs Placebo + training

Primary Outcomes

Measure
Walking Index for Spinal Cord Injury (WISCI II)
time frame: 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.
Peak treadmill velocity
time frame: Compare changes in peak treadmill velocity pre to post training with placebo to pre to post training with Lexapro during a 10-12 week time period.

Secondary Outcomes

Measure
Volitional Strength
time frame: Pre Training (Day 1), Pre Drug B (approx end of week 5), Post-Final (approx end of week 10)
Gait kinematics
time frame: 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)
time frame: 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)
time frame: 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)
time frame: 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)
Modified Ashworth of knee extensors/flexors (modAsh)
time frame: 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)
Spinal Cord Assessment Tool for Spasticity (SCATS)
time frame: 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)

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria

    Exclusion Criteria

      Additional Information

      Official title Monoaminergic Modulation of Motor Function in Subacute Incomplete Spinal Cord Injury
      Description This is a phase I double blinded randomized control clinical trial. The procedures for participation in both Aims of the study are described below in chronological order. Aim 1 and 2: Explanation of the consent form and study procedures/protocol will be performed in the Neurolocomotion laboratory (room 1382), with subjects and their families provided ample time for questions. Subjects are provided substantial time to choose to participate, and are provided the laboratory phone numbers/emails to contact the PI and research personnel with any potential questions. In situations where the subject is unable to be transported to the laboratory, the PI will explain the consent form at a time and location convenient for the subject and/or their family. Subjects will then undergo a screening procedure to determine if they are eligible to participate in the study based on inclusion/exclusion criteria. Aim 1: Modified Ashworth scale (mod Ash, no units) will be used to detect velocity-dependent resistance to passive muscle stretch/joint rotation. The modAsh will grossly assess spasticity at bilateral knee extensors and knee flexors, with scores from 0-5 (1+ scores will be converted to 2 and higher scores increased accordingly). Spinal Cord Assessment Tools for Spasticity (SCATS, no units) will be employed to assess flexor and extensor spasms and clonic activity of the plantarflexors (Benz et al. , 2005). Independence in walking ability will be assessed at each assessment period using the Walking Index for SCI II (WISCI II, which is a 21 point (0-20) ordinal scale which assigns a score based on amount of physical assistance, bracing, and assistive device used to ambulate. Notably, subjects will not be allowed to ambulate with braces extending above the knee. Six minute walk test (m) will be assess walking around a continuous hall-way at subjects' self-selected velocity, with distance determined each minute and summed over the entire six minute duration (van Hedel et al. , 2005). Subjects will be asked to "walk at your (their) normal, comfortable pace" with minimal physical assistance and bracing/devices as needed This measure is significantly association with measures of community walking in subjects with incomplete SCI (Saraf et al. , 2009). BERG balance test will be administered. Gait Mat testing will be performed to guage spatiotemporal aspects of walking. 6 minute walk test will be performed. Lower Extremity Motor Score, Peak treadmill speed (m/s) Aim 2: Same as above including strength evaluations : Ankle, knee, hip flexors/extensors tested bilaterally (Biodex®). Subjects in Aim 2 will be tested at initial evaluation, after four weeks of initial training, and will be repeated after each four weeks of training on either the placebo or study medication. Subjects in Aim 2 will additionally be requested to return for follow up testing after one year. Subjects will be offered to participate in audio, videotaping and/or photography. Women who are of childbearing age and are contemplating becoming pregnant will be required to submit a pregnancy test and must notify the principal investigator immediately.
      Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
      Information provided to ClinicalTrials.gov by Rehabilitation Institute of Chicago.