The Movement of Botulinum Toxin Through the Lateral Gastrocnemius Muscle in Humans: An Expanded Examination
Condition: Stroke; Muscle Spasticity
MeSH terms: Muscle Spasticity
Intervention: Botox
Intervention description: THE PROTOCOL DESCRIPTION ATTEMPTED TO OUTLINE A CONTINGINECY PLAN- MOVING TO ONE OF TWO METHODOLOGOIES DPENDING ON PRELIMINARY FINDINGS. UNFORTUNATLEY, OVER 2 YEARS RECRUITMENT WAS GROSSLY INADEQUATE PREVENTING ANY TYPE OF EVEN CURSURY PRELIMINARY DATA ANALYSIS AND FORCING THE EARLY TERMINATION OF THIS STUDY. MICHAEL W. O'DELL, MD
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: If the within-subject design is used, N=15 and subjects will be randomized 1:1 to receive the standard injection to either the LGM or MGM. The experimental injection will be delivered to the muscle not receiving the standard injection.
If the between-subject design must be used, N=25 and subjects will be randomized 2:3 to receive either the experimental or standard injection to the spastic LGM.
Please note the following:
Standard Injection: 25 units of onobotulinumtoxinA (Botox®) diluted in 0.25cc of saline.
Experimental Injection: 25 units of onobutilinumtoxinA (Botox®) diluted in 0.50cc of saline.
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 30 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: stroke; spasticity

Summary:

      Despite the wide-spread use of botulinum toxin (BT) to treat spasticity (increased muscle
      tone) in central neurological disease, evidence-based guidance on dosing, dilution, and
      injection technique is limited. The wide-spread use of BT in spasticity management, expense
      of these agents, and detrimental impact from movement into non-injected muscles mandates a
      better understanding of BT movement within muscles. A proof-of-concept paper written by
      investigators at Weill Cornell Medicine introduced a non-invasive MRI approach with "voxel
      thresholds" that was able to detect intramuscular effects of BT at 2 and 3 months
      post-injection of BT. The purpose of the current set of studies is to refine this MRI
      technique to better visualize the movement of botulinum toxin through muscle. In addition,
      the investigators plan to explore, using the imaging technique, how spastic muscle and
      differing dilutions affect BT movement in an effort to support the development of better
      research techniques to study toxin movement in human muscle.
    

Eligibility criteria:

        Experimental Group:

        Inclusion Criteria:

          -  Male and female aged 30-75

          -  Diagnosis of any stroke (ischemic or hemorrhagic, first occurrence or recurrent)

          -  Clinically significant lower extremity spasticity as assessed by PI that would benefit
             from BT treatment

          -  Ambulatory with or without device and without assistance at household or greater level

          -  Indication to inject gastrocnemius muscle (any combination of spastic lower extremity
             muscle injections are acceptable)

          -  Goal of treatment may include improvement of gait, ankle range of motion, ankle foot
             orthosis fit, heel strike, ankle position in stance phase, decreased clonus, or relief
             from painful muscle spasms

          -  Naïve to BT of any serotype in any lower extremity muscle

          -  Naïve to phenol or alcohol treatment in any lower extremity muscle

        Exclusion Criteria:

          -  History of concomitant neurological disease (central or peripheral) other than stroke

          -  Contraindication to intramuscular injection of BT

          -  Medically unstable as determined by PI

          -  Have an intrathecal baclofen pump

          -  Contraindication for MRI (Subjects with MRI-compatible hip replacements may
             participate, but not those with total knee replacements due to artifact)