Skin Ulcer Clinical Trial
Official title:
The Regeneration Effects of Derma-PACE Shockwave in Chronic Diabetic Ulcers
Management of chronic diabetic foot skin ulcers require multidisciplinary approaches including diabetic control, wound care, antibiotic, shoe wear off-loading, and surgery in selected cases. The results are inconsistent and irregular, and most studies reported unsatisfactory results. Many adjunctive therapies are implemented in the care of chronic diabetic foot ulcers including hyperbaric oxygen therapy (HBO), ultrasound, recombinant human platelet-derived growth factor-BB (rPDGF-BB), vacuum assisted wound closure (VAWC) and acellular matrix. HBO is the most commonly utilized at the investigators institution. Mixed results of HBO in chronic diabetic foot ulcers are reported. Several studies reported that the beneficial effects of HBO, but none showed universal success. Therefore, the development of a new effective method of treatment for chronic diabetic ulcers is extremely valuable. Extracorporeal shockwave therapy (ESWT) acts as mechanotransduction that produces the therapeutic benefits through complex biological pathways including neovascularization and tissue regeneration. ESWT also showed bacteriostatic effects in experiments. Some studies reported the effectiveness of ESWT in acute and chronic soft tissue wounds. Others reported effectiveness of ESWT in chronic ulcers with 50% completely healed with 6 sessions of treatment. With this background, it appears that ESWT may be effective in the treatment of chronic diabetic foot ulcers. The purpose of this study is to evaluate the efficacy of ESWT in chronic foot ulcers, and to compared with that treated with HBO, and to study the molecular and blood flow perfusion before and after ESWT.
【Background and Purpose】Management of chronic diabetic and ulcers require multidisciplinary
approaches including diabetic control, wound care, antibiotic, shoe wear off loading, and
surgery in selected cases. The results are inconsistent and irregular, and most studies
reported unsatisfactory results. Many adjunctive therapies are implemented in the care of
chronic skin ulcers including hyperbaric oxygen therapy (HBO), ultrasound, recombinant human
platelet-derived growth factor-BB (rPDGF-BB), vacuum assisted wound closure (VAWC) and
acellular matrix. HBO is the most commonly utilized at our institution. Mixed results of HBO
in chronic skin ulcers are reported. Several studies reported the beneficial effects in
chronic skin ulcers, but none showed universal success. Therefore, the development of a new
effective method of treatment for chronic skin ulcers is extremely valuable. Wang et al
demonstrated that extracorporeal shockwave acts as mechanotransduction that produces the
therapeutic benefits through complex biological pathways including neovascularization and
tissue regeneration. Gerdesmeyer et al showed bacteriostatic effects of shockwave in
experiments. Schaden et al reported the effectiveness of extracorporeal shockwave in acute
and chronic soft tissue wounds. Saggini et all reported effectiveness of ESWT in chronic
skin ulcers with 50% completely healed within 6 sessions of treatment. However, no working
mechanism of ESWT was discussed. With this background, it appears that extracorporeal
shockwave may be effective in the treatment of chronic diabetic ulcers. We have conducted a
pilot study using orthowave 180 (TRT, Woodstock, GA) in the treatment of chronic ulcers. The
preliminary results of a pilot study in 26 patients with 31 ulcers showed healed or >50%
improved ulcers in 90%, 10% unchanged and none worse. The results of the pilot study was
published by the Journal of Surgical Research 2009; 152: 96-103. The poster exhibit of this
study won the 1st place award in the category of tumor and metabolism of the 75th AAOS
annual meeting in San Francisco, CA in March 2008. This study continues the research using
derma-PACE (derma-pulse acoustic cellular expression). Derma-PACE (Sanuwave, Alpharetta, GA)
is a new shockwave device designed for the treatment of diabetic ulcers. The purpose of this
study is to evaluate the efficacy and safety of Derma-PACE shockwave device in the treatment
of chronic diabetic ulcers, and to compare the results with that of hyperbaric oxygen
therapy, and to investigate the blood flow perfusion, histopathological examination and
immunohistochemical analysis.
【Patient selection】This study is approved by The Institutional Review Board on Human
Studies. The procedures are performed in accordance with the standards of the Ethical
Committee and the Declaration of Helsinki in 1975. All patients are required to sign an
informed consent prior to participation in the study. The inclusion criteria include
patients with recurrent chronic diabetic ulcers of the extremities for longer than 3 months
duration. The exclusion criteria include patients with cardiac arrhythmia or pacemaker,
pregnancy, skeletal immaturity patients with malignancy, patients with joint sepsis, ulcers
around the skull, spine and chest wall, and patients with poor compliance. A power analysis
revealed that a sample size of 32 in each group would be required to establish the
statistical significance with α = 0.05 and power = 0.8. We anticipate a drop-out rate of 10
to 15% for various reasons during the course of treatment. Therefore, we plan to recruit 100
patients in the study. Patients are randomly divided into two groups with 50 patients in the
shockwave group, and 50 patients in the HBO group who are treated with HBOT. All patients
receive the same protocol of diabetic control, wound care, antibiotics and corrective shoe
wear etc. Pre-treatment evaluations include complete history and physical examination,
chemistry and coagulation profiles, detailed past surgical and medical treatments. The
ankle-brachial index (AKI) and HBA1C are assessed individually.
【Technical descriptions】 【Shockwave application】The derma-PACE device is set at E2 @ 4 Hz
with the energy level at 0.11 mJ/mm² energy flux density. The dosage of shockwave is wound
size dependent. The treatment area includes the actual wound area extended 1.0 cm periphery
in every direction. The number of pulses = treatment area (cm²) x 8, but in any case at
least 500 shocks. The treatment is performed twice/week for a total of 6 treatments.
【Hyperbaric Oxygen Therapy】Patients receive hyperbaric oxygen therapy (HBO) in a sealed
multi-place chamber at a pressure of 2.5 atmospheres absolute (ATA). The treatment starts
with the compression of air pressure from 1 ATA to 2.5 ATA in 15 minutes. Patients breathe
with 100% medical grade O2 with mask for 25 minutes and take off the mask for O2 break for 5
minutes, and then, repeat breathing 100% O2 with mask for another 25 minutes and off mask
for O2 break for 5 minutes. At the end of treatment, the chamber air pressure is
decompressed from 2.5 ATA with O2 mask to 1 ATA in 15 minutes. Each patient receives HBO
daily, five days a week for a total of 40 treatments.
【Evaluation parameters:】The evaluation parameters include clinical assessment, local blood
flow perfusion, bacteriological examination, histopathological evaluation and
immunohistochemical analysis from the biopsy specimens. The ulcers are quantitatively
assessed using the S(AD)SAD classification for the size, shape and configuration with
photo-documentation before and after treatment. The neuropathic sensory change of the foot
is examined with pin-prick test. The circulatory status of the affected limb is evaluated
with digital palpation of the dorsalis pulsation and ultrasound Doppler perfusion scan.
Local blood flow perfusion scan, bacterial culture and sensitivity, and biopsy from the
periphary of the ulcer including normal skin is performed before and after treatment, and
the specimens are subjected to histomorphological examination and immunohistochemicial
stain. The data before and after treatment within the same group and the data between the
two groups will be analyzed statistically.
【Anticipated work schedules and results:】We estimate to enroll 2 to 3 patients per week, and
it will take approximately one year to recruit sufficient number of patients. It will
require 12 additional months for follow-up. Therefore, we estimate a total of three years to
complete this study. We anticipate favorable results of ESWT in chronic diabetic ulcers. We
also anticipate superior results with ESWT over HBO therapy. Furthermore, we anticipate the
improvement in local blood flow perfusion, antibacterial effect as well as angiogenesis and
tissue regeneration effects after ESWT. This novel method of treatment may bring in a new
insight in the management of chronic diabetic ulcers. Shockwave has the potential to cure
chronic skin ulcers without surgery and directly benefits thousands of patients who suffer
from this disastrous disease.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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