The Regeneration Effects of Derma-PACE Shockwave in Chronic Diabetic Ulcers
Description:
【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.
Condition:
Skin Ulcer
Treatment:
Derma-PACE
Start Date:
February 2009
Sponsor:
Chang Gung Memorial Hospital
For More Information:
https://clinicaltrials.gov/show/NCT01219127