- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01753882
Monoaminergic Modulation of Motor Function in Subacute Incomplete Spinal Cord Injury (SCI)
Monoaminergic Modulation of Motor Function in Subacute Incomplete Spinal Cord Injury
Study Overview
Detailed 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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Illinois
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Chicago, Illinois, United States, 60611
- Rehabilitation Institute of Chicago
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
A) Subjects with motor incomplete SCI (AIS C or D) of 1-9 mo. duration will be selected, with anatomical lesions between C1-T10.
B) Subjects will be between 18 and 75 years of age . Note: grant application states 16-75, however, we will be only including subjects 18-75.
C) All subjects must be previously ambulatory with passive range of motion consistent with normal walking, and must include: ankle dorsiflexion ankle to 10° and plantarflexion to 30°, knee flexion from 0 to 90°, hip flexion/extension to 90° - -10°.
D) Subjects will be medically stable with medical clearance to participate, with absence of concurrent severe medical illness, including unhealed decubiti, existing infection, significant cardiovascular or metabolic disease which limits exercise participation, 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, and history of pulmonary complications, including significant obstructive and/or restrictive lung diseases.
E) Individuals who are undergoing concurrent physical therapy will not be excluded from the study population, secondary to the use of the cross-over design. Physical therapy records will be obtained to ascertain the amount and types of physical therapy services being provided.
F) Women of childbearing potential will not be excluded, although women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the pharmacological agents on the developing fetus.
G) 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. These complications will be partially obviated by requiring all patients to undergo specific medical procedures (liver function tests, urinalysis) prior to admission.
H)Men and women will be recruited for participation in the proposed clinical trial at rates consistent with national and local average of gender disparities of SCI (80% male, 20% women). Women of childbearing potential will not be excluded, although women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the test agent (SSRIs) on the developing fetus. Women who use oral contraceptives will not be assessed for TIZ experiments and will be excluded from Aim 1.
I) Individuals of different ethnicities will be recruited at rates similar to the national and local ethnicity rates. Current data since 2005 indicate that of the entire population of SCI, 66.1% are Caucasian, 27.1% are African American, 6.6% are of Hispanic origin, and 2.0% are Asian. These populations closely resemble those at RIC and in our previous studies in human SCI.
Exclusion Criteria:
A) Subjects who are ventilator-dependent will be excluded secondary to severely impaired respiratory capacity.
B) Subjects with substantial orthopedic bracing to stabilize the cervical or thoracic vertebral column and are unable to fit in the safety harness without increased risk of injury are not eligible.
C) Patients will also be excluded if they are unable to tolerate 10 minutes of standing without orthostasis (decrease in blood pressure by 20 mmHg systolic and 10 mmHg diastolic); previous experience in the sub-acute population suggests that 10 minutes of standing is more than sufficient for tolerating 45 minutes of walking secondary to increased activity/muscle pump minimizing risk for orthostasis.
D) Women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the pharmacological agents on the developing fetus.
E) Subjects with height and weight limitations which restrict participation in Lokomat Training(LT) will be excluded. For height, subjects who are > 78 inches or < 60 inches tall may present with thigh/shank lengths that may limit use of the Lokomat. If subjects are not able to step independently on the treadmill and require use of robotic-assistance during treadmill stepping, attempts to fit all subjects in the robotic orthosis prior to enrollment and randomization. For weight, the maximum weight limit for use of the safety harness/counterweight system is 300 lbs.
F) Individuals with concurrent severe medical illness, including unhealed decubiti, existing infection, significant cardiovascular or metabolic disease which limits exercise participation, 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, and history of pulmonary complications, including significant obstructive and/or restrictive lung diseases will be excluded.
G) Patients prescribed other anti-depressant medications, including specific monoaminergic agents, their precursors or their agonists, or other medications with known interactions to the SSRIs or TIZ will be excluded. With consultation and supervision of the patients' physician and the attending physicians for each individual patient, subjects will be required to wean of their medications on an appropriate and safe dosing schedule to minimize side effects of drug cessation or withdrawal. All subjects 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 washout period for SSRIs and a 72 hour washout for TIZ will be utilized.
H) All subjects prescribed anti-spastic medications will be excluded. Specific agents to be excluded include baclofen (Lioresal®) and benzodiazepines (Diazepam®). Selected agents used for pain modulation will be evaluated per subject to ascertain potential interactions with test agent. With consultation and supervision of the patients' physician and the attending physicians for each individual patient, subjects will be required to wean of their medications on an appropriate and safe dosing schedule to minimize side effects of drug cessation or withdrawal. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 72-hour minimum washout period for all such medications will be utilized. (Note: exception to use of TIZ during training - see above).
I) Women of childbearing potential will not be excluded, although women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the test agent (SSRIs) on the developing fetus. Women who use oral contraceptives will not be assessed for TIZ experiments and will be excluded from Aim 1.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Gait Training with Lexapro
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.
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Agent + training vs Placebo + training
Other Names:
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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.
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Agent + training vs Placebo + training
Other Names:
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What is the study measuring?
Primary Outcome Measures
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.
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Evaluation of bracing, assistive device, and assistance required for ambulation
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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.
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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.
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During graded treadmill test
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Volitional Strength
Time Frame: Pre Training (Day 1), Pre Drug B (approx end of week 5), Post-Final (approx end of week 10)
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Ankle, knee, hip flexors/extensors strength (Nm) tested bilaterally (Biodex®)
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Pre Training (Day 1), Pre Drug B (approx end of week 5), Post-Final (approx end of week 10)
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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)
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Kinematic excursions of hip/knee/ankle (Motion Analysis®)
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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)
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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)
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Subject walks a distance of 10m with the middle 6m being timed.
Instructions to walk normal comfortable pace.
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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)
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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)
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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.
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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)
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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)
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Measure of lower extremity muscle strength on 0-5 point scale.
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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)
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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)
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Measure of spasticity of knee flexors and extensors during passive range of motion
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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)
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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)
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Measure of spasticity tested in supine
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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)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Central Nervous System Diseases
- Nervous System Diseases
- Trauma, Nervous System
- Spinal Cord Diseases
- Wounds and Injuries
- Spinal Cord Injuries
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Citalopram
Other Study ID Numbers
- STU00056589
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.
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