Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies
Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies
The purpose of this feasibility study is to determine if temporary weakness of a small foot
 muscle caused by local injection of botulinum toxin into that muscle can be measured with a
 strain gauge in addition to the previously known valid measurements via nerve conduction
 studies and surface electromyogram.
Purpose/Hypothesis:

 Verify the validity and reliability of strain gauge assessment of strength of extensor
 digitorum brevis (EDB) muscle compared to compound muscle action potential (CMAP) size from
 EDB and surface electromyography (SEMG) data from EDB after injection of botulinum toxin into
 EDB

 1. Primary Outcome Measure:

 Change in measured strength (using strain gauges) of dorsiflexion of digits 3 and 4
 ("strength of EDB") after vs. before botulinum toxin injection into EDB

 2. Secondary Outcome Measures:

 1. Change in CMAP (with standard reference electrode location and with an "inactive"
 reference electrode location) from EDB after vs. before botulinum toxin injection
 into EDB;

 2. Change in SEMG parameters from EDB, tibialis anterior (TA), and extensor digitorum
 longus (EDL) after vs. before botulinum toxin injection into EDB

 STUDY DESIGN:

 1. Overview:

 Single intramuscular injection of botulinum toxin or placebo (placebo or BOTOX 2 units
 or BOTOX 20 units, each with a total volume of 0.1 ml) intramuscular into right EDB on
 Day 0. Strain gauge data and SEMG data from TA and EDL are obtained at each evaluation
 time: Baseline (3 separate times prior to Day 0 after at least 5 separate training
 sessions for the strain gauges); Day 1; Day 2; Day 4 (during anticipated rapid change);
 Day 14 (+/-1 day) (at clinical nadir); Day 21 (+/-1 day) (another day at clinical
 nadir); and Month 4 (when clinical recovery from the effect of BOTOX should have
 occurred); CMAP & SEMG data from EDB are obtained at Baseline; Day 4 (close to nadir of
 CAMP); Day 14 (at nadir of CAMP) and/or Day 21 (at nadir of CAMP); and Month 4 (when
 clinical recovery from the effect of BOTOX should have occurred but CMAP should not have
 recovered).

 2. Protocol:

 Single-center, Double-Blind, Randomized, Pilot Trial Total Sample Size: 12-15

 Treatment Groups:

 BOTOX Single Dose 20 units IM in EDB in 0.1 ml BOTOX Single Dose 2 units IM in EDB in 0.1 ml
 Placebo (Saline) Single Dose IM in EDB in 0.1 ml

 Estimated Time to Enroll:

 0-3 months

 Estimated Study Duration:

 4-6 months
Inclusion Criteria:

 -  Normal, healthy, male or female subjects, 18 to 54 years of age.

 -  Written informed consent has been obtained.

 -  Females with child-bearing potential have a negative urine pregnancy test and agree to
 use a reliable form of contraception during the study.

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

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

 Exclusion Criteria:

 -  Abnormality by focused history and examination including the presence of foot
 deformity.

 -  Abnormal (as determined by the investigator) screening nerve conduction studies of the
 lower limbs.

 -  Identification of anomalous innervation of right EDB via screening nerve conduction
 studies.

 -  The subject having a foot which does not adequately fit in the modified ankle-foot
 orthosis used with the strain gauge.

 -  The subject having a foot in which anatomic bone landmarks cannot be adequately
 identified.

 -  Body mass index (BMI) greater than 30.

 -  History of significant (as determined by the investigator) lower limb injury or lower
 limb surgery

 -  Any uncontrolled clinically significant medical condition.

 -  Known allergy or sensitivity to any of the components in the study medication.

 -  Females with a positive pregnancy test, or who are breast-feeding, planning a
 pregnancy during the study, who think that they may be pregnant at the start of the
 study, or females of childbearing potential who are unable or unwilling to use a
 reliable form of contraception during the study.

 -  Concurrent participation in another investigational drug or device study or
 participation within 3 months prior to study.

 -  Treatment with botulinum toxin of any serotype prior to enrollment in study or prior
 clinical botulism.

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

 -  Evidence of alcohol abuse, drug abuse, or other relevant neuropsychiatric condition.

 -  Infection or skin disorder at an anticipated injection site.

 -  Any condition or situation that, in the investigator's opinion, may put the subject at
 significant risk, confound the study results (e.g. variable strength on serial testing
 during screening examination; or foot, toe, or ankle pain that may limit full
 participation in muscle strength testing), or interfere significantly with the
 subject's participation in the study.