Evaluation of BOTOX® With Rehabilitation Therapy for the Treatment of Wrist and Hand Spasticity in Post-Stroke Patients

After a stroke, patients commonly experience tightness in their affected arm from wrist and
hand muscle overactivity called spasticity. Spasticity is difficult to manage with only one
type of treatment. Usual treatments of spasticity are not very effective and may produce
unwanted side effects. Untreated spasticity may result in muscular problems and decrease a
patient's general ability to function and thus affect his/her quality of life.

BOTOX®, a botulinum toxin type A produced from Clostridium botulinum, blocks certain
chemicals that cause spasticity. With appropriate injections of BOTOX® in the correct
muscle, it can change the tightness in the muscle temporarily. Published reports indicate
that several hundred adult patients with arm and/or leg spasticity of various causes (e.g.,
poststroke, multiple sclerosis and traumatic brain injury) have benefited from injections of
BOTOX® in the spastic muscle. The efficacy of BOTOX® in patients with post-stroke
spasticity in their arms and hands has been demonstrated in seven phase 2 placebo-controlled
studies and two phase 3 studies.

The present study is designed to determine the safety and effectiveness of injections of
BOTOX® in spastic muscles of the arm and hand compared with injections of saline (which
would do nothing) when combined with rehabilitation therapy for the improvement of active
function tasks in post-stroke patients. Injections will be targeted to reduce common
spasticity patterns of the arm and hand which include: bent elbow, palm down forearm, bent
wrist, thumb-in-palm, clenched fist, and other hand deformities. This will be done only at
Emory University. Neither the doctor injecting the drug nor the subject receiving the drug
will know if they are getting BOTOX® or saline. Which type of injection the subject
receives will be completely randomized (like flipping a coin). All subjects will have
rehabilitation therapy after their injections. Subjects will be assessed at a total of 5
scheduled visits (qualification (Week 1), Injection (Week 2), Evaluations on Weeks 8, 10,
and 14. All subjects will receive rehabilitation therapy immediately after their injections
for 1 hour a day, 3-5 times a week, for 4 weeks. The results from this project will provide
valuable data on the ability of BOTOX® and physical rehabilitation to provide effective
treatment to spastic muscles of the arm and hand after stroke. This project has the
potential to increase the availability of effective rehabilitation techniques to patients
with stroke.

Inclusion Criteria:

- Male or female, 18 to 70 years of age

- Written informed consent

- Written Authorization for Use and Release of Health and Research Study Information
has been obtained

- Medically stable condition in the investigator's opinion

- History of stroke (hemorrhagic or ischemic) that resulted in a unilateral, upper-limb
focal spasticity pattern of the wrist and fingers

- EMG evidence of volitionary activiation of wrist and finger extensor and flexor
muscles

- Active range of motion (to be repeated 3 times by the patient): The ability to
initiate wrist extension of at least 10 degrees from a fully flexed position with the
forearm supported and stabilized in a pronated position. Active shoulder flexion and
abduction to 45 degrees and no less than -30 degrees of elbow extension.

- Mini-Mental State Exam (MMSE) >24

- If on an anti-spasticity medication regiment at the time of qualification, the dose
regimen must have been stable 1 month prior to study enrollment

- Ability to follow study instructions and likely to complete all required visits

Exclusion Criteria:

- Time since neurological event resulting in upper limb spasticity less than 3 months
or greater than 24 months

- Previous therapy with BOTOX® or any other botulinum toxin serotype for any condition
within the last 12 months

- Phenol or alcohol block in the study limb within 6 months of study enrollment visit

- History (within 3 months of qualification) of or planned (during study period)
casting of the study limb

- Current treatment with an intrathecal baclofen pump

- In the opinion of the investigator, profound atrophy of the muscles in the study limb
that are targeted for injection

- Previous surgical intervention in the study limb, except for routine orthopedic
repair for bone fractures, in the last 6 months

- Presence of fixed contracture of the study limb impairing functional activity

- Clinically significant inflammation or condition in the study limb that, in the
investigator's opinion, could limit joint movement (other than stroke or spasticity)

- Clinically significant spasticity or contracture of the elbow (defined as an Ashworth
score >3) or shoulder in the study limb, in the investigator's opinion would limit
sue of the wrist and fingers

- Changes in oral spasticity medications within 30 days of enrollment (dose of
anti-spasticity medications should remain the same during the study)

- Anticipated use of oral coagulants during the study

- Known allergy or sensitivity to the study medication or its components

- Infection or dermatological condition at anticipated injection sites

- Current participation in another clinical study or within 1 month of the enrollment
visit

- Females who are pregnant, nursing, or planning a pregnancy during the study, or
females of childbearing potential, not using a reliable means of contraception

- Anticipated use during the study of concurrent therapies for treatment of upper motor
neuron syndrome (eg, acupuncture)

- Any medical condition that may put the patient at increased risk with exposure to
BOTOX including diagnosed myasthenia gravis, Eaton-Lambert Syndrome, amyotrophic
lateral sclerosis, or any other disorder that might interfere with neuromuscular
function

- Patient has a condition or is in a situation which in investigator's opinion may put
the patient significant risk, may confound the study results, or may interfere
significantly with patient's participation in the study