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

NCT ID: NCT00822523

Last Updated: 2018-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-07-31

Brief Summary

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.

Detailed Description

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

Conditions

Muscle Strength; Botulinum Toxins, Type A

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

Botulinum toxin type A, 20 units

Single intramuscular (into extensor digitorum brevis muscle of the foot) dose of Botulinum toxin type A, 20 units

Group Type: EXPERIMENTAL

Botulinum Toxin, Type A

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Botulinum Toxin, Type A

Intervention Type: DRUG

2 units, single dose, intramuscular to right EDB muscle

Placebo

Saline, Single dose, Intramuscular injection into right EDB

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Single Dose, Intramuscular into right EDB muscle

Interventions

Botulinum Toxin, Type A

20 units, single dose, intramuscular in right EDB muscle

Intervention Type: DRUG

Botulinum Toxin, Type A

2 units, single dose, intramuscular to right EDB muscle

Intervention Type: DRUG

Saline

Single Dose, Intramuscular into right EDB muscle

Intervention Type: DRUG

Other Intervention Names

BOTOX; BOTOX; Placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 54 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Allergan

INDUSTRY

Sponsor Role: collaborator

Loma Linda University

OTHER

Sponsor Role: lead

Responsible Party

Gordon Peterson

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gordon W Peterson, MD

Role: PRINCIPAL_INVESTIGATOR

Loma Linda University

Locations

Electromyography Laboratory, Loma Linda University Medical Center

Loma Linda, California, United States

Loma Linda University

Loma Linda, California, United States

Countries

United States

References

Sloop RR, Escutin RO, Matus JA, Cole BA, Peterson GW. Dose-response curve of human extensor digitorum brevis muscle function to intramuscularly injected botulinum toxin type A. Neurology. 1996 May;46(5):1382-6. doi: 10.1212/wnl.46.5.1382.

Reference Type: BACKGROUND

PMID: 8628486 (View on PubMed)

Hamjian JA, Walker FO. Serial neurophysiological studies of intramuscular botulinum-A toxin in humans. Muscle Nerve. 1994 Dec;17(12):1385-92. doi: 10.1002/mus.880171207.

Reference Type: BACKGROUND

PMID: 7969239 (View on PubMed)

Other Identifiers

58360

Identifier Type: -

Identifier Source: org_study_id