Enhanced Ultrasound Treatment of Chronic Wounds With Monitoring of Healing and Quality of Life Outcomes

The two most common types of chronic wounds are venous ulcers (VUs) and diabetic ulcers
(DUs). The investigators will conduct the first double-blind randomized controlled trial
(RCT) to test the effect of low-frequency, low-intensity (LFLI) ultrasound (US) on chronic
wound healing and health related quality of life (HRQOL) with high statistical confidence (α
< 0.05, power > 0.90, n=60 VUs, n=60 DUs). The investigators' approach combines this active
therapy with non-invasive diagnostic monitoring of wound hemodynamics throughout the
treatment cycle, and includes analysis of the impact of nutritional status and inflammation
on wound closure. There are several innovative aspects of this work. Specifically, (1) The
lightweight, battery-powered applicator is the first potentially wearable ultrasound wound
therapy device that is safe to apply for extended periods of time. (2) The applicator
actively promotes healing, which is fundamentally different from commercial ultrasonic
systems that remove necrotic tissue only. (3) The study approach will link LFLI US exposure
to changes in wound hemodynamics and HRQOL, which has the potential to enable personalized
medicine. (4) The analysis of patient nutritional and systemic inflammatory status may enable
further treatment customization by identifying those patients most likely to benefit from
LFLI US therapy. (5) The study approach incorporates both disease-specific and generic
measures of HRQOL, which is unique for a therapeutic ultrasound RCT.

The low-frequency, low-intensity (20 kiloHertz (kHz), <100 milliWatt per square centimeter
(mW/cm2) spatial peak-temporal peak), portable ultrasound applicator is lightweight (<25g)
and permits safe and clinically pragmatic wound treatment. The field parameters of the US
device were previously optimized for venous ulcers, and three recent pilot clinical human
studies (VUs: n=20, n=25; DUs: n=10) demonstrated that the treatment improved healing by 15%
per week compared to sham treatment. The investigators therefore anticipate that our
treatment will accelerate closure of chronic wounds, and hypothesize that (1) LFLI US will
improve generic and disease-specific HRQOL scores, (2) LFLI US will activate beneficial
changes in the microvasculature of the wound and surrounding tissue, and (3) individuals with
poor nutrition and high levels of inflammation will have delayed wound healing.

The specific aims are to: (1) Assess the effect of LFLI US on VUs and DUs by measuring wound
closure as a primary endpoint and generic and disease-specific HRQOL as secondary endpoints.
(2) Monitor the effects of LFLI US on wound perfusion and oxygenation using non-invasive
optical methods, and (3) Determine the impact of nutritional status and inflammation on
closure of DUs and VUs. Overall, this work will validate LFLI US as a safe, portable, and
cost-effective therapy for chronic wounds. This is important because new therapies and
improved clinical paradigms for wound management are urgently needed. Over the long-term, the
study findings may enable the development of personalized wound treatment regimens across
care settings.

Inclusion Criteria:

- Have a venous ulcer (VU) or diabetic ulcer (DU) that has been documented for at least
8 weeks without complete re-epithelialization and is larger than 0.75 cm2 in size.

- VUs must be present on the lower extremities non-weight-bearing areas.

- DUs must be present on the ankle or foot and be secondary to complications from
diabetes.

- Patients with DUs must have a documented history of diabetes mellitus of at least six
months.

Exclusion Criteria:

- VUs secondary to any connective tissue disorder or blood dyscrasias.

- Severe vascular insufficiency (ankle-brachial index lower than 0.75 or toe-brachial
index below 0.5).

- Active, untreated infection

- Acute deep venous thrombosis

- Cutaneous malignancy present on the involved extremity

- Active (or past 6 months) cancer treatment

- Presence of both a diabetic ulcer and a venous ulcer on the same extremity

- Known allergy to Tegaderm (a polyurethane dressing)

- Pregnant women

- Individuals younger than 18 years of age regardless of emancipation status

- Prisoners

- Individuals unable to speak English, Spanish, or Mandarin

- Adults unable to consent