Trial Outcomes & Findings for Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies (NCT NCT00822523)

Results Overview

The force of dorsiflexion of the combination of digits 2 and 3 (at the same time using a single loop) of the foot were measured using a strain gauge after and before the administration of Botulinum Neurotoxin type A (BoNT/A) or placebo. The baseline value was the mean of the 3 values for force obtained prior to injection of BoNT/A. The baseline was compared with the subsequent values.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

13 participants

Primary outcome timeframe

Baseline (3 times) then following single injection of botulinum toxin into EDB with testing at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4

Results posted on

2018-09-05

Participant Flow

Participant milestones

Participant milestones
Measure	Botulinum Toxin Type A, 20 Units Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Overall Study STARTED	5	4	4
Overall Study COMPLETED	5	4	4
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total n=13 Participants Total of all reporting groups	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Age, Categorical <=18 years	0 Participants n=483 Participants	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=483 Participants	5 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=483 Participants	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	29.2 years STANDARD_DEVIATION 2.3 • n=483 Participants	31 years STANDARD_DEVIATION 5.9 • n=93 Participants	26.8 years STANDARD_DEVIATION 2.1 • n=4 Participants	29.5 years STANDARD_DEVIATION 2.0 • n=27 Participants
Sex: Female, Male Female	5 Participants n=483 Participants	2 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants
Sex: Female, Male Male	8 Participants n=483 Participants	3 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Region of Enrollment United States	13 participants n=483 Participants	5 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (3 times) then following single injection of botulinum toxin into EDB with testing at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4

The force of dorsiflexion of the combination of digits 2 and 3 (at the same time using a single loop) of the foot were measured using a strain gauge after and before the administration of Botulinum Neurotoxin type A (BoNT/A) or placebo. The baseline value was the mean of the 3 values for force obtained prior to injection of BoNT/A. The baseline was compared with the subsequent values.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Baseline	7.63 kg Standard Deviation 3.31	5.16 kg Standard Deviation 1.48	10.43 kg Standard Deviation 5.33
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Day 1	7.85 kg Standard Deviation 3.76	4.28 kg Standard Deviation 1.02	12.22 kg Standard Deviation 8.26
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Day 2	9.37 kg Standard Deviation 3.21	4.46 kg Standard Deviation 1.22	10.88 kg Standard Deviation 7.21
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Day 4	10.42 kg Standard Deviation 6.56	4.85 kg Standard Deviation 0.75	11.38 kg Standard Deviation 9.59
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Day 14	7.89 kg Standard Deviation 3.7	4.75 kg Standard Deviation 1.00	13.46 kg Standard Deviation 8.49
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Day 21	9.60 kg Standard Deviation 4.51	4.20 kg Standard Deviation 2.11	11.88 kg Standard Deviation 6.82
Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB Month 4	7.62 kg Standard Deviation 4.44	5.27 kg Standard Deviation 1.37	11.23 kg Standard Deviation 6.92

SECONDARY outcome

Timeframe: Baseline 1 (mean of 3 measurement on the same day of testing) compared with Baseline 2 (mean of 3 measurement on the same day of testing) on a second day compared with Baseline 3 (mean of 3 measurement on the same day of testing)

Population: Normal controls at baseline before BoNT/A injected

The force of dorsiflexion of the combination of digits 2 and 3 (at the same time using a single loop) of the foot were measured using a strain gauge on three different days prior to injection of BoNT/A or placebo. On each of the three days of baseline testing, the force was defined as the mean of three different measurements, separated by at least 1 minute from another measurement.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Stability of Baseline Measurements of Force Baseline 1	7.78 kg Standard Deviation 4.29	4.83 kg Standard Deviation 1.21	11.15 kg Standard Deviation 5.28
Stability of Baseline Measurements of Force Baseline 2	7.58 kg Standard Deviation 3.38	5.28 kg Standard Deviation 1.81	9.82 kg Standard Deviation 5.29
Stability of Baseline Measurements of Force Baseline 3	7.51 kg Standard Deviation 2.47	5.35 kg Standard Deviation 1.70	10.32 kg Standard Deviation 5.46

SECONDARY outcome

Timeframe: Force measured at Day 14 after BoNT/A injction into EDB and Force measured at Day 21 after BoNT/A injction into EDB.

The force of dorsiflexion of the combination of digits 2 and 3 (at the same time using a single loop) of the foot were measured using a strain gauge after and before the administration of Botulinum Neurotoxin type A (BoNT/A). The force at each day of testing was the mean of the 3 values for force obtained on that day. Value is percent change from baseline. Comparison is made between the percent change from baseline force and the force on Day 14 in each group vs. the percent change from baseline force and the force on Day 21 in each group.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Difference in Force From Day 14 to Day 21 Day 14	4.57 percent change from baseline Standard Deviation 19.66	-4.81 percent change from baseline Standard Deviation 20.94	22.66 percent change from baseline Standard Deviation 32.22
Difference in Force From Day 14 to Day 21 Day 21	27.01 percent change from baseline Standard Deviation 27.44	-19.58 percent change from baseline Standard Deviation 41.04	15.15 percent change from baseline Standard Deviation 32.15

SECONDARY outcome

Timeframe: At each visit for nerve conduction studies following injection of onabotulinumtoxinA (botulinum type A neurotoxin) into EDB (Day 0; Day 4; Day 14; Month 4)

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Number of Participants With Serious Adverse Effects to onabotulinumtoxinA (Botulinum Type A Neurotoxin)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 1000 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-42.43 percent change from baseline Standard Deviation 19.82	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-52.35 percent change from baseline Standard Deviation 27.17	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-39.76 percent change from baseline Standard Deviation 11.26	—

SECONDARY outcome

Timeframe: Baseline (mean of 3 measurement on the same day of testing) then following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4

Measure the percent change of the Surface Electromyogram (SEMG) as measured by the Mean Rectified Voltage (MRV) with a window of 500 ms from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A or placebo. Each MRV represents the mean of 3 individual measurements of the MRV at that timepoint with measurements at least 60 seconds apart. In order to facilitate comparison from one subject to the next, the MRV is then converted into percent change from baseline for that subject.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 Participants Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Percent Change of the Surface Electromyogram (SEMG) MRV-500 From EDB After vs. Before Botulinum Toxin Injection Into EDB. Day 4	-40.4 percent change from baseline Standard Deviation 20.0	-44.4 percent change from baseline Standard Deviation 7.6	-4.1 percent change from baseline Standard Deviation 69.6
Percent Change of the Surface Electromyogram (SEMG) MRV-500 From EDB After vs. Before Botulinum Toxin Injection Into EDB. Day 14	-50.8 percent change from baseline Standard Deviation 27.4	-52.2 percent change from baseline Standard Deviation 14.6	0.7 percent change from baseline Standard Deviation 38.2
Percent Change of the Surface Electromyogram (SEMG) MRV-500 From EDB After vs. Before Botulinum Toxin Injection Into EDB. Month 4	-39.2 percent change from baseline Standard Deviation 9.4	-19.8 percent change from baseline Standard Deviation 25.0	-28.6 percent change from baseline Standard Deviation 56.4

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 500 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-42.09 percent change from baseline Standard Deviation 21.19	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-51.94 percent change from baseline Standard Deviation 28.01	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-40.67 percent change from baseline Standard Deviation 11.48	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 200 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-39.89 percent change from baseline Standard Deviation 22.65	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-51.75 percent change from baseline Standard Deviation 28.52	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-39.90 percent change from baseline Standard Deviation 12.43	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 1000 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-40.92 percent change from baseline Standard Deviation 18.90	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-51.03 percent change from baseline Standard Deviation 26.56	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-37.86 percent change from baseline Standard Deviation 9.45	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 500 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-40.44 percent change from baseline Standard Deviation 20.00	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-50.72 percent change from baseline Standard Deviation 27.40	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-39.22 percent change from baseline Standard Deviation 9.42	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in the standard location at the base of the ipsilateral 5th toe after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 200 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Day 4	-53.81 percent change from baseline Standard Deviation 21.81	-37.35 percent change from baseline Standard Deviation 21.98	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Day 14	-63.78 percent change from baseline Standard Deviation 21.77	-49.49 percent change from baseline Standard Deviation 28.49	—
Correlation in Percent Change of the CMAP (With Standard Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Month 4	-48.38 percent change from baseline Standard Deviation 26.16	-38.44 percent change from baseline Standard Deviation 9.32	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 1000 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Day 4	-67.37 percent change from baseline Standard Deviation 29.18	-42.43 percent change from baseline Standard Deviation 19.82	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-52.35 percent change from baseline Standard Deviation 27.17	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 1000 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-39.76 percent change from baseline Standard Deviation 11.26	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 500 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Day 4	-67.37 percent change from baseline Standard Deviation 29.18	-42.09 percent change from baseline Standard Deviation 21.19	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-51.94 percent change from baseline Standard Deviation 28.01	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 500 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-40.67 percent change from baseline Standard Deviation 11.48	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Root Mean Squared with 200 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-39.90 percent change from baseline Standard Deviation 12.43	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Day 4	-67.37 percent change from baseline Standard Deviation 29.18	-39.89 percent change from baseline Standard Deviation 22.65	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Root Mean Squared With 200 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-51.75 percent change from baseline Standard Deviation 28.52	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 1000 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-51.03 percent change from baseline Standard Deviation 26.56	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-37.86 percent change from baseline Standard Deviation 9.45	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 1000 ms Window). Day 4	-67.37 percent change from baseline Standard Deviation 29.18	-40.92 percent change from baseline Standard Deviation 18.90	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 500 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-50.72 percent change from baseline Standard Deviation 27.40	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Day 4	-67.37 percent change from baseline Standard Deviation 29.18	-40.44 percent change from baseline Standard Deviation 20.00	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 500 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-39.22 percent change from baseline Standard Deviation 9.42	—

SECONDARY outcome

Timeframe: Mean of 3 measurements on the same day of testing following single injection of botulinum toxin into EDB with testing at Day 4; Day 14; and Month 4 each compared with Baseline measurement

Population: Analysis of the 2 Units Botox and placebo arms was to be done only if the arm with 20 Units Botox showed significant changes in the strain gauge measurements.

Measure the percent change of the Compound Muscle Action Potential (CMAP) Amplitude from extensor digitorum brevis (EDB) with the reference electrode in an "inactive" location at the ipsilateral medial malleolus after injection of BoNT/A into EDB compared with before injection of BoNT/A. Each CMAP represents the mean of 3 individual measurements of the CMAP at that timepoint. In order to facilitate comparison from one subject to the next, the CMAP is then converted into percent change from baseline for that subject. CMAP percent change is then correlated with the percent change in the Surface Electromyography as measured by the Mean Rectified Voltage with 200 millisecond window at the same time points after injection. Group with injection of 20 units BoNT/A is used.

Outcome measures

Outcome measures
Measure	Botulinum Toxin Type A, 20 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=5 Participants Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Day 14	-74.00 percent change from baseline Standard Deviation 24.46	-49.49 percent change from baseline Standard Deviation 28.49	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Month 4	-52.40 percent change from baseline Standard Deviation 33.13	-38.44 percent change from baseline Standard Deviation 9.32	—
Correlation in Percent Change of the CMAP (With "Inactive" Reference Electrode Location) From EDB After vs. Before Botulinum Toxin Injection Into EDB vs. Percent Change Surface Electromyography (as Measured by Mean Rectified Voltage With 200 ms Window). Day 4	67.37 percent change from baseline Standard Deviation 29.18	-37.35 percent change from baseline Standard Deviation 21.98	—

Adverse Events

Botulinum Toxin Type A, 20 Units

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Botulinum Toxin, Type A, 2 Units

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Botulinum Toxin Type A, 20 Units n=5 participants at risk Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units Botulinum Toxin, Type A: 20 units, single dose, intramuscular in right EDB muscle	Botulinum Toxin, Type A, 2 Units n=4 participants at risk Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 2 units Botulinum Toxin, Type A: 2 units, single dose, intramuscular to right EDB muscle	Placebo n=4 participants at risk Saline, Single dose, Intramuscular injection into right EDB Saline: Single Dose, Intramuscular into right EDB muscle
Musculoskeletal and connective tissue disorders Decreased sensation	20.0% 1/5 • Number of events 1	0.00% 0/4	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Flu like symptoms	60.0% 3/5 • Number of events 3	0.00% 0/4	0.00% 0/4
Nervous system disorders Mild Headache	0.00% 0/5	25.0% 1/4 • Number of events 1	0.00% 0/4

Additional Information

Gordon Perterson, MD

Loma Linda University

Phone: 909-558-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place