Botulinum Toxin A Adult Gastrocnemius Muscle Study (BTX-A)

An Efficacy Comparison of Botulinum Toxin A Injection Into Two Different Sites in Gastrocnemius Muscle for the Treatment of Spastic Patients, Randomized Controlled Trial

The study aims to compare the effectiveness of BOTOX-A® (botulinun toxin A) placed between two different injection sites, namely at the proximal portion of the gastrocnemius(GCM) versus at the midbelly of the GCM.

Study Overview

• Status: Completed
• Conditions: Stroke; Muscle Spasticity
• Intervention / Treatment: Drug: BOTOX-A®

Detailed Description

Previous studies have used the midbelly of a muscle as the position where the motor endplates are most densely located. The reasoning behind this method was based on the previous works that showed most bands of cholinesterase activity to be located in specific topographical patterns at the center of the muscle fiber. These results have been used as landmarks to place the injections. Current standard guidelines recommend that botulinum toxin be placed at the 4 quadrants of the midbelly portion of the gastrocnemius (GCM) muscle. However, recent cadaveric research studies on the distribution of the intramuscular endings of the GCM suggest that the highest branch density is found within the upper 20-30% length of the calf. Therefore, in accordance to the theory that effect of botulinum toxin are greatest at sites where the intramuscular endings are most dense, the location where these toxins should be placed would be at these proximal sites of the GCM rather than at the midbelly.

40 recruited patients will be allocated into either the intramuscular ending targeted (ie.upper portion of calf) or midbelly targeted group.

Each subject will undergo a total number of 4 assessments; prior to the injection and 2,4and 8 weeks post injection.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Kyounggido
    • Bucheon, Kyounggido, Korea, Republic of
      • Department of Rehabilitation Medicine Bucheon St Mary's Hospital, Catholic University of Korea, College of Medicine
  • Kyoungido
    • Songnam, Kyoungido, Korea, Republic of
      • Bobath Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, 20 < age < 70 year old
• Hemiplegia documented after ischemic or hemorrhagic stroke, documented by CT (computed tomography) or MRI (magnetic resonance imaging) scan
• Time between the onset of stroke < 24 months
• Individuals who have been medically stable for at least 4 weeks prior to study enrollment
• Confirmed equinovarus with spastic hypertonia of the ankle
• Spasticity as defined by a MAS greater than grade 1 +
• Botulinum toxin -naive patients
• Participants who can complete the 10 meter walking test with caregiver or walking tool assistance within 8 and 45 seconds, on 2 occasions
• Participants who will have stable treatment regimen and concomitant medication during the trial period

Exclusion Criteria:

• The patient has any of the following medical conditions that is contraindication to botulinum toxin exposure; pregnancy, lactation, neuromuscular disease, aminoglycoside, antibiotic concurrent to botulinum toxin treatment
• Fixed contracture of the ankle, previous history of surgical procedure performed on the ankle
• Cognitive deficit that disables patients to give informed consent to the procedure
• Concomitant progression of any CNS (central nervous system) or PNS (peripheral nervous system), or myopathy, or uncontrolled seizure. Underlying CNS insult should be controlled and in stable condition with no further risk of progression and further deterioration of patient's current neurological status. Those with multiple sclerosis or multiple systemic atrophy are to be excluded
• Significant cutaneous or joint inflammation
• URI or other systemic infection that would mandate the use of antibiotic concurrent to botulinum toxin injection
• Anticoagulation treatment with INR (International Normalized Ratio) greater than 3.0
• Upper extremity spasticity greater than MAS grade 4 that may limit gait function
• Subjects with previous episodes of motor point block injection using phenol or other chemodenervating agents
• Subjects with intrathecal baclofen pump

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intramuscular ending Targeting; Botox 200 units placed at the upper 2/10-3/10 length of the GCM	Drug: BOTOX-A®; 200 units, single treatment only; Other Names: Generic Name: Botulinum toxin type A
ACTIVE_COMPARATOR: Midbelly Targeting; A total of 200 units will be placed at the four quadrants of the midbelly portion of the GCM.	Drug: BOTOX-A®; 200 units, single treatment only; Other Names: Generic Name: Botulinum toxin type A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline for EMG (electromyogram) activity	Surface EMG	week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline of GCM tone a measured on the Modified Ashworth Scale (MAS)		Change from baseline at 8 weeks
Change from baseline of Ankle Range of motion	Passive range of motion of the ankle at resting state with the use of goniometer	Change from baseline at 8 weeks
Change from baseline of gait speed with 10 meters walk test	Change from baseline at 8 weeks	Change from baseline at 8 weeks
Change from baseline of ABILOCO scale		Change from baseline at 8 weeks
Change from baseline of Disability Assessment Scale		Change from baseline at 8 weeks
Change from baseline of Functional Ambulation Category Scale		Change from baseline at 8 weeks
Change of baseline of Lindmark Modified Fugyl Meyer Scale		Change from baseline at 8 weeks
Change from baseline of Tardieu angle of ankle		Change from baseline at 8 weeks

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Collaborators: Bobath Memorial Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (ESTIMATE): January 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): May 15, 2012
• Last Update Submitted That Met QC Criteria: May 14, 2012
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Stroke; Ankle; Lower extremity; Muscle spasticity; Botulinum Toxins
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: BCMC10AH07