Serotonergic Modulation of Motor Function in Subacute and Chronic SCI

April 18, 2019 updated by: Thomas G Hornby, Shirley Ryan AbilityLab
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proposed study will consist of a double-blinded, randomized controlled trial using a crossover design to assess the effects of SSRIs (escitalopram oxalate, Lexapro®, Forest Pharmaceuticals, Inc) and 5HT-antagonists (cyproheptadine [CYPRO], Periactin ®, Merck, Inc) on volitional and spastic motor behaviors in subjects with motor incomplete SCI following both acute and chronic medication delivery. Voluntary and reflexive motor behaviors in 120 subjects with SCI will be assessed. These interventions will be applied to individuals with acute (< 6 months post injury) chronic (> 1 year post injury) motor incomplete SCI to determine both the rate and extent of changes in volitional motor performance and involuntary spastic behaviors. For the training portion of the study (referred to as subproject 2 below), a portion of the acute and chronic subjects will be evaluated every 2 weeks for up to16 weeks and participate in locomotor training, to investigate and better understand changes in motor function and recovery in individuals with spinal cord injuries. Following 2-4 weeks of this training, individuals will be given either the study drug, or placebo and continue evaluation and training. Following an additional 4 weeks, subjects will be given either the placebo or study drug (whichever they did not receive during the prior 4 weeks). The order will be randomized.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Rehabilitation Institute of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Gait Training with Placebo
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
Agent + training vs Placebo + training
Other Names:
  • microcrystalline dextrose
Experimental: Gait Training with Lexapro
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
Agent + training vs Placebo + training
Other Names:
  • escitalopram

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Kinematic excursions of hip/knee/ankle (Motion Analysis®)
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)
Subject walks a distance of 10m with the middle 6m being timed. Instructions to walk normal comfortable pace.
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)
Subject asked to walk normal comfortable pace for 6 minutes. Total distance is recorded. Subject can take rest breaks as needed but are encouraged to continue walking throughout the 6 minutes.
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)
Measure of spasticity tested in supine
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)
Volitional Strength
Time Frame: Pre Training (Day 1), Pre Drug B (approx end of week 5), Post Final (approx end of week 10)
Ankle, knee, hip flexors/extensors strength (Nm) tested bilaterally (Biodex®)
Pre Training (Day 1), Pre Drug B (approx end of week 5), 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)
Measure of lower extremity muscle strength on 0-5 point scale
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)
Measure of spasticity of knee flexors and extensors during passive range of motion
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)
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.
Peak treadmill speed during graded treadmill testing
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shirley Ryan AbilityLab

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Thomas G Hornby, PhD, PT, Rehabiltiation Institute of Chicago/UIC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2016

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 11, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU00014259

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings