Efficacy and Functional Outcomes of Botulinum Toxin A Injections to Hamstrings in Flexed Knee Gait in Cerebral Palsy

Efficacy and Functional Outcomes of Botulinum Toxin A Injections to Hamstrings in Flexed Knee Gait in Cerebral Palsy: A Double-Blind, Randomized, Placebo-Controlled Trial

The study proposes to determine if injections of BTX-A to the hamstring muscles result in measurable physiologic changes not observed with normal saline injections in children with spastic diplegic cerebral palsy who walk with a flexed-knee gait pattern.

Study Overview

• Status: Completed
• Conditions: Spastic Diplegic Cerebral Palsy
• Intervention / Treatment: Drug: Botulinum Toxin A

Detailed Description

This study proposes to: (1) to determine if injections of BTX-A to the hamstring muscles result in measurable physiologic (body structure and body function) changes not observed with normal saline injections, in children with spastic diplegic CP who walk with a flexed-knee gait pattern; (2) to assess whether physiologic changes translate into functional (activity and participation) improvements; (3) to evaluate family's perception of change in function, activity, participation, and quality of life.

This study will demonstrate if BTX-A injected into overactive hamstring muscles of children with spastic cerebral palsy (CP) and a flexed-knee walking pattern has measurable effects across the spectrum of dimensions of disablement of the International Classification of Functioning, Disability, and Health (ICF). It is a multi-center, prospective, randomized, double-blind trial comparing results of injection of BTX- A and placebo saline in controls, into overactive hamstring muscles, using multiple outcomes measures. Temporal-spatial gait parameters, instrumented 3DGA kinematics, passive ROM, spasticity measurement with both Ashworth and Tardieu scales, muscle strength/control, Gross Motor Function Measurement (GMFM), Pediatric Outcomes Data Collection Instrument (PODCI), Gillette Functional Assessment Questionnaire (FAQ), 6-Minute Walk Test, and Goal Attainment Scale (GAS), assessing all ICF domains, will be collected at baseline and at 1 month, 3 months, and 6 months post-injection. Power analysis demonstrates the need to randomize 250 children (125 with BTX-A, 125 with saline), allowing for attrition. Nine participating hospitals will contribute patients.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Spastic cerebral palsy;
2. Bilateral lower extremity involvement;
3. Spasticity present in the hamstrings;
4. Flexed knee gait >15 degrees by observation (OGS);
5. Age between 3 and 18 years old; (
6. GMFCS Level I to Level IV; (
7. Able to walk a minimum of 4 complete steps without resting with and without braces/shoes a minimum of 3 times;
8. Able to follow simple commands;
9. Cooperative with physicians and therapist;
10. Able to tolerate application of equipment to the skin.

Exclusion Criteria:

1. Rhizotomy surgery within the last 1 year;
2. Lower extremity surgical procedures (soft tissue or bony) within the past 1 year;
3. Currently implanted and operating Intrathecal Baclofen Pump (oral baclofen OK);
4. Lower extremity BTX-A injections within the past 6 months;
5. Multilevel BTX-A injections;
6. Gait trainer reliance;
7. Serial casting 3 months prior to or during study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
3DGA Kinematics
Passive Range of Motion
Spasticity Measurement with AShworth and Tardieu Scales
Muscle Strength and Control

Secondary Outcome Measures

Outcome Measure
6-Minute Walk Test
Gross Motor Function Measurement (GMFM)
Pediatric Outcomes Data Collection Instrument (PODCI)
Gillette Functional Assessment Questionnaire (GFAQ)
Goal Attainment Scale (GAS)

Collaborators and Investigators

• Sponsor: Shriners Hospitals for Children
• Collaborators: Washington University School of Medicine; University of Virginia
• Investigators: Principal Investigator: Philip E. Gates, MD, Shriners Hospitals for Children

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Study Completion (ACTUAL): December 1, 2007

Study Registration Dates

• First Submitted: November 30, 2005
• First Submitted That Met QC Criteria: November 30, 2005
• First Posted (ESTIMATE): December 2, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): February 5, 2009
• Last Update Submitted That Met QC Criteria: February 4, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: spasticity; cerebral palsy; diplegia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Cerebral Palsy; Paralysis; 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: 9199