Intrathecal (IT) Baclofen Drug Distribution

Study Overview
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Brief Summary
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The goal of this pilot study to determine whether there is a significant therapeutic advantage to place the ITB catheter within the cervical, thoracic or lumbar region of the spine. It is also a goal of this pilot study to determine whether the origin of spasticity influences the effect of Lioresal Intrathecal (baclofen injection) on ITB catheters located in the cervical, thoracic or lumbar regions of the spine. The investigators propose to study the impact of catheter location on the reduction in spasticity within a group of patients who are scheduled for ITB trial.

Detailed Description
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While ITB therapy is commonly recommended for treatment of severe spasticity due to a variety of diseases, the location of optimal drug (baclofen) delivery has not been defined in a controlled study. Furthermore, the cost of pharmacological management in these patients is significant, and optimal location for drug delivery through an implantable drug pump may have significant impact on the cost burden of maintenance refills. It is the goal of this pilot study to determine whether there is a significant therapeutic advantage to place the ITB catheter within the cervical, thoracic or lumbar region of the spine. It is also a goal of this pilot study to determine whether the origin of spasticity influences the effect of Lioresal Intrathecal (baclofen injection) on ITB catheters located in the cervical, thoracic or lumbar regions of the spine. The investigators propose to study the impact of catheter location on the reduction in spasticity within a group of patients who are scheduled for ITB trial. In studying the impact of catheter location among patients with spinal versus cerebral origin of spasticity, the disease origin may also have a significant impact on baclofen dosing relative to the placement of the catheter. In addition, the pharmacokinetic half-life and the variability of intrathecal baclofen is poorly understood as data is limited. In order to provide initial data regarding CSF baclofen washout, samples of spinal fluid obtained just prior to- and following IT baclofen administration will be obtained for delayed analysis. The results of these pharmacological analysis may refine the understanding of how quickly baclofen is distributed from a given catheter location, and whether it is affected by catheter location or disease origin. Since multiple catheter locations will be studied within a given patient, it also affords the opportunity to sample small amounts of CSF at key anatomical sites along the spinal axis as a secondary objective.

Official Title
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Intrathecal (IT) Baclofen Drug Distribution Pilot Study

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Drug: Baclofen bolus injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with spasticity from spinal origin (spinal cord injury) Adult patients with spasticity of cerebral origin (cerebral palsy and cerebrovascular accident) Adult women of child bearing age with a negative pregnancy test Exclusion Criteria: Patients with spasticity from Multiple sclerosis Pregnant women Patients under the age of 18 years Patients over the age of 50 Patients who are unable to have an MRI scan of the total spine Patients with spinal deformity that would prevent easy access to the lumbar intrathecal space Patients who have an allergic reaction to IT baclofen Patients who have significant headache from CSF withdrawal Patients who have intradural blockage that prevents advancing the IT catheter to the level of C4

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baclofen injection at designated spinal level<br>Days 2,3,4,5 a baclofen injection bolus will be given in the catheter, located at C4, T4, T10 and L2 respectively. Effect of baclofen injection (50 microgram bolus) upon rigidity will be assessed manually using the Modified Ashworth rating score for selected upper and lower extremities. | Drug: Baclofen bolus injection<br>* A baclofen bolus injection (50 micrograms) will be administered daily after the patient returns from radiology to position catheter injection location. The injection may be given at C4, T4, T10 or L2 spinal locations depending on the catheter tip location.<br>* Other names: Injection of baclofen bolus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | The Modified Ashworth Scale (MAS) is a 6-point scale (Standard MAS scale values: 0, 1, 1.5, 2, 3, or 4) used to evaluate spasticity based on grading muscle tone by moving joints. The MAS scores in this cohort are measured in biceps, triceps and forearm flexor muscles in upper extremities; and quadriceps, hamstrings and gastrocnemius muscles in lower extremities. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Improvement in spasticity was a reduction in MAS score by 1 point across a joint tested. Maximal MAS change is the sum of MAS score reduction in all four limbs tested. This outcome looks at subjects with spasticity of cerebral origin. | Baseline to 6 hours post-injection | 
| Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | The Modified Ashworth Scale (MAS) is a 6-point scale (Standard MAS scale values: 0, 1, 1.5, 2, 3, or 4) used to evaluate spasticity based on grading muscle tone by moving joints. The MAS scores in this cohort are measured in biceps, triceps and forearm flexor muscles in upper extremities; and quadriceps, hamstrings and gastrocnemius muscles in lower extremities. The score ranges from 0 (no increase in muscle tone) to 4 (affected part(s) rigid in flexion or extension). Improvement in spasticity was a reduction in MAS score by 1 point across a joint tested. Maximal MAS change is the sum of MAS score reduction in all four limbs tested. This outcome looks at subjects with spasticity of spinal origin. | Baseline to 6 hours post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injury, cerebral palsy, stroke