Dose-response Relationship of Botullinum Toxin (DWP 450) for Finger Flexor Spasticity

Study Overview
=================
Brief Summary
-----------------
Study Design: Randomized Single Blind Study Objective: To determine the dose relationship of DWP 450 for finger flexor spasticity Subjects: 78 patients with upper extremity spasticity after CVA Inclusion criteria: Patient who have spasticity (MAS greater than 2 in finger flexors) Methods: Patients will be randomly assigned to one of 5 groups. Gp 1: placebo, Gp 2: 15U, Gp 3: 30 U, Gp 4: 50 U, Gp 5: 75 U

Detailed Description
-----------------
Seventy-eight patients with upper extremity spasticity after cerebrovascular accident will be recruited and randomly assigned to one of 5 groups. The groups are as followings. Gp 1: placebo group (Normal saline 1.2 ml) Gp 2: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U Gp 3: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U Gp 4: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U Gp 5: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U According to the group, the injection will be performed to the finger flexor musles (flexor digitorum superficialis and profundus). Outcome measurement will be MAS (Modified ashworth scale), FMA, Wolf Motor Assessment, Cross sectional area measured by Ultrasonography. Patient evaluation will be conducted 2 weeks, 1 months, 2 months, and 3 months after the injection.

Official Title
-----------------
Dose-response Relationship of Botullinum Toxin (DWP 450) for Finger Flexor Spasticity

Conditions
-----------------
Spasticity as Sequela of Stroke

Intervention / Treatment
-----------------
* Drug: Normal Saline 0.9% 1.2 ml
* Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U
* Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U
* Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U
* Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: over 6 weeks after stroke onset MAS (modified Ashworth scale) greater than 2 in finger flexor Exclusion Criteria: neuromuscular junction disease or motor neuron disease phenol or alcohol block for the target limbs within 6 months before screening botulinum toxin injection within 3 months before screening history or plan for tendon lengthening surgery significant contracture ormuscle atrophy at the target joint or muscle concurrent treatment with intrathecal baclofen hypersensitivity or allergy to study drug or its components pregnancy or planned pregnancy, breastfeeding abnormal lab findings for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and serum creatinine.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal Saline 0.9% 1.2 ml will be injected to finger flexor muscles | Drug: Normal Saline 0.9% 1.2 ml<br> <br> |
| Experimental: Treatment dose 15<br>Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U will be injected to finger flexor muscles | Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 15 U<br> <br> * Other names: Nabota (DWP 450);|
| Experimental: Treatment dose 30<br>Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U will be injected to finger flexor muscles | Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 30 U<br> <br> * Other names: Nabota (DWP 450);|
| Experimental: Treatment dose 50<br>Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U will be injected to finger flexor muscles | Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 50 U<br> <br> * Other names: Nabota (DWP 450);|
| Experimental: Treatment dose 70<br>Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U will be injected to finger flexor muscles | Drug: Clostridium Botulinum Toxin Type A (Nabota, DWP 450) 70 U<br> <br> * Other names: Nabota (DWP 450);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAS (Modified Ashworth Scale) | Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension | baseline | 
| MAS (Modified Ashworth Scale) | Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension | 2wks after injection | 
| MAS (Modified Ashworth Scale) | Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension | 4wks after injection | 
| MAS (Modified Ashworth Scale) | Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension | 8wks after injection | 
| MAS (Modified Ashworth Scale) | Spasticity measurement measures resistance during passive soft-tissue stretching(taken from Bohannon and Smith, 1987): 0: No increase in muscle tone Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension 1+: Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved Considerable increase in muscle tone, passive movement difficult Affected part(s) rigid in flexion or extension | 12wks after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ultrasonography | measurement of changes of cross sectional area | baseline | 
| Ultrasonography | measurement of changes of cross sectional area | 2wks after injection | 
| Ultrasonography | measurement of changes of cross sectional area | 4wks after injection | 
| Ultrasonography | measurement of changes of cross sectional area | 8wks after injection | 
| Ultrasonography | measurement of changes of cross sectional area | 12wks after injection | 
| Fugl Myer Upper Extremity Assessment | measurement of upper extremity function | baseline | 
| Fugl Myer Upper Extremity Assessment | measurement of upper extremity function | 2 wks after injection | 
| Fugl Myer Upper Extremity Assessment | measurement of upper extremity function | 4 wks after injection | 
| Fugl Myer Upper Extremity Assessment | measurement of upper extremity function | 8 wks after injection | 
| Fugl Myer Upper Extremity Assessment | measurement of upper extremity function | 12 wks after injection | 
| Wolf Motor Assessment | measurement of upper extremity function | baseline | 
| Wolf Motor Assessment | measurement of upper extremity function | 2 wks after injection | 
| Wolf Motor Assessment | measurement of upper extremity function | 4 wks after injection | 
| Wolf Motor Assessment | measurement of upper extremity function | 8 wks after injection | 
| Wolf Motor Assessment | measurement of upper extremity function | 12 wks after injection |