Diabetes Mellitus, Peripheral Neuropathy, Plantar Ulcers
Conditions
Keywords
Diabetes mellitus, plantar ulcers, peripheral neuropathy
Brief summary
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.
Detailed description
Please read Brief Summary
Interventions
DRUGBotulinum 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
DRUGSaline
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
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plantar Flexor Muscle Strength | Pre-treatment, 2 weeks after injection, upon ulcer healing, 3 months and 6 months after ulcer healing | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Barefoot Plantar Pressure | pre-injection, 2 weeks post injection, post healing, and 3 and 6 months post healing | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group Placebo (saline) injections into 6 sites in the calf muscle | 5 |
| 200 Units of Botox Total 200 units of Botulinum Toxin injected into 6 sites into the calf muscles. | 7 |
| 300 Units of Botox 300 units of botulinum toxin injected into 6 sites in the calf muscle | 5 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 |
| Overall Study | Too ill to participate | 0 | 1 | 0 |
| Overall Study | Ulcer did not heal | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo Group | 200 Units of Botox | 300 Units of Botox | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 4 Participants | 15 Participants |
| Region of Enrollment United States | 5 participants | 7 participants | 5 participants | 17 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 7 | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 | 0 / 5 |
Outcome results
Primary
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.
Time frame: Pre-treatment, 2 weeks after injection, upon ulcer healing, 3 months and 6 months after ulcer healing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin 200 Units | Plantar Flexor Muscle Strength | -8 Plantar Flexor Torque (Nm) | Standard Deviation 11 |
| Placebo | Plantar Flexor Muscle Strength | 3 Plantar Flexor Torque (Nm) | Standard Deviation 4 |
| Botulinum Toxin 300 Units | Plantar Flexor Muscle Strength | 6 Plantar Flexor Torque (Nm) | Standard Deviation 10 |
Secondary
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.
Time frame: pre-injection, 2 weeks post injection, post healing, and 3 and 6 months post healing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin 200 Units | Barefoot Plantar Pressure | -4 Peak Plantar Pressure (N/cm^2) changes | Standard Deviation 16 |
| Placebo | Barefoot Plantar Pressure | 0 Peak Plantar Pressure (N/cm^2) changes | Standard Deviation 11 |
| Botulinum Toxin 300 Units | Barefoot Plantar Pressure | 0 Peak Plantar Pressure (N/cm^2) changes | Standard Deviation 5 |