Botulinum Toxin Effects on Plantar Ulcer Recurrence

The purpose of this grant is to collect pilot data to assess the amount of botulinum toxin that needs to be injected into the calf muscles of subjects with diabetes mellitus, peripheral neuropathy, and a plantar ulcer to decrease muscle strength. We hypothesize that a decrease in plantar flexor muscle strength will temporarily decrease plantar pressure. The decrease in plantar pressure will provide temporary protection to the new tissue as it gains tolerance to high stress with the long term potential outcome as a decrease in the ulcer recurrence rate.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Peripheral Neuropathy; Plantar Ulcers
• Intervention / Treatment: Drug: Saline; Drug: Botulinum Toxin

Detailed Description

Please read "Brief Summary"

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63108
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of diabetes mellitus and determination of diminished or absent plantar sensation
• A recurrent forefoot plantar ulcer; at least the second occurrence of a plantar ulcer or a previous failure to heal a plantar ulcer with reasonable treatment intervention (Total contact casting, off loading boot, molded ankle foot orthotic, Gillette, or therapeutic footwear modifications)
• Ambulatory

Exclusion Criteria:

• Active infection in the involved foot
• Previous botulinum toxin injections
• Ulcers on the dorsal surface of the foot
• Ankle-brachial index <0.45
• History of cerebral vascular accident or other neurological problems complicating their rehabilitation
• Women of childbearing years unless pregnancy test is agreed upon, completed, and negative and agree to use some form of contraception during the study.
• Current drug therapy that includes an anticoagulant
• History of a neuromuscular disease, except peripheral neuropathy as a result of diabetes mellitus

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 1; Placebo (saline) injections into 6 sites in the calf muscle	Drug: Saline; Placebo (saline) (3cc). Injection are given at one session. 2 injections into the medial gastrocnemius, 2 injections into the lateral gastrocnemius, and 2 injections into the soleus
ACTIVE_COMPARATOR: 2; Total 200 units of Botulinum Toxin injected into 6 sites into the calf muscles.	Drug: Botulinum Toxin; 200 units of botulinum toxin, and 300 units of botulinum toxin. Injection are given at one session. 2 injections into the medial gastrocnemius, 2 injections into the lateral gastrocnemius, and 2 injections into the soleus; Other Names: botox
ACTIVE_COMPARATOR: 3; 300 units of botulinum toxin injected into 6 sites in the calf muscle	Drug: Botulinum Toxin; 200 units of botulinum toxin, and 300 units of botulinum toxin. Injection are given at one session. 2 injections into the medial gastrocnemius, 2 injections into the lateral gastrocnemius, and 2 injections into the soleus; Other Names: botox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plantar Flexor Muscle Strength	Concentric plantar flexor torque was assessed using the Biodex System 3 Pro Orthopedic Testing & Rehabilitation dynamometer. Plantar flexor peak torque was measured at 60 deg/sec, which is comparable to the angular velocity of the ankle joint during the stance phase of walking. Three trials of each foot were completed. Peak torque was calculated as the average of the two highest torque values across trials and results were expressed as Nm. A positive value represents an increase in torque while a negative value represents a decrease in torque.	Pre-treatment, 2 weeks after injection, upon ulcer healing, 3 months and 6 months after ulcer healing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Barefoot Plantar Pressure	Novel emed pressure platform was used for data collection. A two-step method of data collection was used and a minimum of two trials of each foot were recorded. The plantar pressure map was divided into 3 horizontal masks using Percent Mask software and peak plantar pressure was determined for the forefoot region. Results are expressed in N/cm^2.	pre-injection, 2 weeks post injection, post healing, and 3 and 6 months post healing

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Mary K Hastings, PT, DPT, ATC, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): March 1, 2010

Study Registration Dates

• First Submitted: February 16, 2009
• First Submitted That Met QC Criteria: February 17, 2009
• First Posted (ESTIMATE): February 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): February 3, 2012
• Last Update Submitted That Met QC Criteria: February 1, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: peripheral neuropathy; Diabetes mellitus; plantar ulcers
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Skin Diseases; Endocrine System Diseases; Disease Attributes; Leg Ulcer; Skin Ulcer; Foot Diseases; Neuromuscular Diseases; Diabetes Mellitus; Foot Ulcer; Ulcer; Peripheral Nervous System Diseases; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: 04-0493; R21HD048972 (NIH)