Spinal Cord InjuryPhase 1NCT01788969
Serotonergic Modulation of Motor Function in Subacute and Chronic SCI
A Phase 1 study testing Lexapro in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Lexapro
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Rehabilitation Institute of Chicago
Chicago, Illinois, 60611
About this study
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.
Read the 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.
- Conditions
- Spinal Cord Injury
- Being tested
- Lexapro, Placebo
- Keywords
- Gait training, Lexapro, Tizanidine
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LexaproDrug
Also called escitalopram
Agent + training vs Placebo + training
PlaceboDrug
Also called microcrystalline dextrose
Agent + training vs Placebo + training
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Walking Index for Spinal Cord Injury (WISCI II)
Evaluation of bracing, assistive device, and assistance required for ambulation
Measured: 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
Ankle, knee, hip flexors/extensors strength (Nm) tested bilaterally (Biodex®)
Measured: Pre Training (Day 1), Pre Drug B (approx end of week 5), Post Final (approx end of week 10)
Gait kinematics
Kinematic excursions of hip/knee/ankle (Motion Analysis®)
Measured: 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)
Subject walks a distance of 10m with the middle 6m being timed. Instructions to walk normal comfortable pace.
Measured: 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)
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.
Measured: 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)
Measure of lower extremity muscle strength on 0-5 point scale
Measured: 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)
Measure of spasticity of knee flexors and extensors during passive range of motion
Measured: 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)
Measure of spasticity tested in supine
Measured: 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
Peak treadmill speed during graded treadmill testing
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2013 (estimated)
- Study startJun 2005
- Primary completionDec 2016
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas G Hornby, Shirley Ryan AbilityLab
- Investigators
- Thomas G Hornby, PhD, PT, Principal investigator, Rehabiltiation Institute of Chicago/UIC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01788969
- Sponsor's protocol ID
- STU00014259
- Status last verified
- Apr 2019
- First submitted
- 7 Feb 2013
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serotonergic Modulation of Motor Function in Subacute and Chronic SCI
- ClinicalTrials.gov ID
- NCT01788969
- Acronym / sponsor ID
- STU00014259
- Conditions
- Spinal Cord Injury
- Keywords
- Gait training, Lexapro, Tizanidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2019 (estimated)
- First posted
- 11 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gait Training with Lexapro | Experimental | Drug: LexaproGait 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. |
| Gait Training with Placebo | Active comparator | Drug: PlaceboGait 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LexaproAlso: escitalopramAgent + training vs Placebo + training | Drug | Gait Training with Lexapro |
| PlaceboAlso: microcrystalline dextroseAgent + training vs Placebo + training | Drug | Gait Training with Placebo |
Primary outcome
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
8 secondary outcomes
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)
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas G Hornby, PhD, PT principal investigator
Rehabiltiation Institute of Chicago/UIC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lexapro in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2019.