Muscle Spasticity
Conditions
Keywords
spinal cord injury, cerebral palsy, stroke
Brief summary
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
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.
Interventions
DRUGBaclofen bolus injection
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.
Sponsors
Medtronic
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1. Adult patients with spasticity from spinal origin (spinal cord injury) 2. Adult patients with spasticity of cerebral origin (cerebral palsy and cerebrovascular accident) 3. Adult women of child bearing age with a negative pregnancy test
Exclusion criteria
1. Patients with spasticity from Multiple sclerosis 2. Pregnant women 3. Patients under the age of 18 years 4. Patients over the age of 50 5. Patients who are unable to have an MRI scan of the total spine 6. Patients with spinal deformity that would prevent easy access to the lumbar intrathecal space 7. Patients who have an allergic reaction to IT baclofen 8. Patients who have significant headache from CSF withdrawal 9. Patients who have intradural blockage that prevents advancing the IT catheter to the level of C4
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | Baseline to 6 hours post-injection | 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. |
| Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | Baseline to 6 hours post-injection | 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. |
Countries
United States
Participant flow
Recruitment details
All subjects recruited through Vanderbilt University Adult Neurosurgery group in Nashville, TN. Intent was to enroll subjects until 20 completed the study. Hence 7 more subjects were enrolled than completed. That makes 27 that started the study and 20 completed it. .
Participants by arm
| Arm | Count |
|---|---|
| Baclofen Injection at Designated Spinal Level 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.
Baclofen bolus injection: 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. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Catheter dislodgement | 1 |
| Overall Study | Could not advance catheter | 1 |
| Overall Study | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Baclofen Injection at Designated Spinal Level | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 21 Participants | — |
| Age, Continuous | 43 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 21 participants | — |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 13 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 1 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
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.
Time frame: Baseline to 6 hours post-injection
Population: Subjects with pre-surgical diagnosis of spasticity of cerebral origin.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | Cervical level 4 injection site | 8 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | Thoracic level 3 injection site | 7 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | Thoracic level 10 injection site | 3 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin | Lumbar lever 2 injection site | 3 Participants |
Primary
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.
Time frame: Baseline to 6 hours post-injection
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | Cervical spine level 4 injection site | 4 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | Thoracic level 3 injection site | 2 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | Thoracic level 10 injection site | 5 Participants |
| Subjects With Max MAS Change | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin | Lumbar level 2 injection site | 3 Participants |