ITB: Intrathecal (IT) Baclofen Drug Distribution
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vanderbilt University | Nashville | Tennessee | United States | 37232 |
Sponsors and Collaborators
- Vanderbilt University
- Medtronic
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Albright AL, Turner M, Pattisapu JV. Best-practice surgical techniques for intrathecal baclofen therapy. J Neurosurg. 2006 Apr;104(4 Suppl):233-9.
- Albright AL. Technique for insertion of intraventricular baclofen catheters. J Neurosurg Pediatr. 2011 Oct;8(4):394-5. doi: 10.3171/2011.7.PEDS11211.
- Coffey JR, Cahill D, Steers W, Park TS, Ordia J, Meythaler J, Herman R, Shetter AG, Levy R, Gill B, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg. 1993 Feb;78(2):226-32.
- Grabb PA, Guin-Renfroe S, Meythaler JM. Midthoracic catheter tip placement for intrathecal baclofen administration in children with quadriparetic spasticity. Neurosurgery. 1999 Oct;45(4):833-6; discussion 836-7.
- Kroin JS, Ali A, York M, Penn RD. The distribution of medication along the spinal canal after chronic intrathecal administration. Neurosurgery. 1993 Aug;33(2):226-30; discussion 230.
- Penn RD. Catheter implant systems for intrathecal drug delivery. J Neurosurg. 1996 Apr;84(4):713.
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Study Results
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. . |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Baclofen Injection at Designated Spinal Level |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 27 |
| COMPLETED | 20 |
| NOT COMPLETED | 7 |
Baseline Characteristics
| Arm/Group Title | Baclofen Injection at Designated Spinal Level |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 21 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
21
100%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Full Range) ] | |
| Mean (Full Range) [years] |
43
|
| Sex: Female, Male (Count of Participants) | |
| Female |
8
38.1%
|
| Male |
13
61.9%
|
| Race and Ethnicity Not Collected (Count of Participants) | |
| Region of Enrollment (participants) [Number] | |
| United States |
21
100%
|
Outcome Measures
| Title | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Cerebral Origin |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects with pre-surgical diagnosis of spasticity of cerebral origin. |
| Arm/Group Title | Subjects With Max MAS Change |
|---|---|
| Arm/Group Description | Days 2,3,4,5 a baclofen injection bolus will be given in the catheter, located at C4, T3, 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. |
| Measure Participants | 20 |
| Cervical level 4 injection site |
8
38.1%
|
| Thoracic level 3 injection site |
7
33.3%
|
| Thoracic level 10 injection site |
3
14.3%
|
| Lumbar lever 2 injection site |
3
14.3%
|
| Title | Subjects Experiencing Maximal MAS Change From Baseline - Spasticity of Spinal Origin |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Subjects With MAS Change - Based on Site of Injection |
|---|---|
| Arm/Group Description | Days 2,3,4,5 a baclofen injection bolus will be given in the catheter, located at C4, T3, 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. |
| Measure Participants | 20 |
| Cervical spine level 4 injection site |
4
19%
|
| Thoracic level 3 injection site |
2
9.5%
|
| Thoracic level 10 injection site |
5
23.8%
|
| Lumbar level 2 injection site |
3
14.3%
|
Adverse Events
| Time Frame | 5 days | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Baclofen Injection at Designated Spinal Level | |
| Arm/Group Description | Days 2,3,4,5 a baclofen injection bolus will be given in the catheter, located at C4, T3, 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. | |
All Cause Mortality |
||
| Baclofen Injection at Designated Spinal Level | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | |
Serious Adverse Events |
||
| Baclofen Injection at Designated Spinal Level | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/27 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Baclofen Injection at Designated Spinal Level | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/27 (3.7%) | |
| Nervous system disorders | ||
| Catheter dislodgement | 1/27 (3.7%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Peter Konrad, MD PhD - PI |
|---|---|
| Organization | Vanderbilt University Medical Center |
| Phone | 6153439822 |
| peter.konrad@vumc.org |
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