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

The purpose of this study is to evaluate the effect of low frequency, low intensity ultrasound treatment on wound healing and health-related quality of life with a randomized clinical trial of patients with venous ulcers or diabetic ulcers.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Foot Ulcer; Venous Ulcer
• Intervention / Treatment: Device: Low Frequency, Low Intensity Ultrasound; Device: Sham Applicator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Temple University School of Podiatric Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low Frequency, Low Intensity Ultrasound; Low Frequency, Low Intensity therapeutic ultrasound applied weekly for up to 16 weeks.	Device: Low Frequency, Low Intensity Ultrasound; Therapeutic ultrasound (20 kHz, <100 mW/cm2 spatial peak-temporal peak)
SHAM_COMPARATOR: Sham Ultrasound; Sham ultrasound applied weekly for up to 16 weeks.	Device: Sham Applicator; Sham ultrasound applicator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in wound size	Percentage change in wound size over 4 weeks	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound closure	Complete wound closure at 16 weeks	16 weeks
Health Related Quality of Life (HRQOL)	Short form health survey will be administered to assess changes in HRQOL	16 weeks, then 6 and 12 months after last treatment
Wound Quality of Life (WQOL)	Health survey will be administered to assess changes in wound-related HRQOL	16 weeks
Wound oxyhemoglobin concentration change	Change in wound oxyhemoglobin concentration per week, measured with diffuse near infrared spectroscopy (DNIRS)	16 weeks
Microcirculatory blood flow index change	Change in microcirculatory blood flow index per week, measured with diffuse correlation spectroscopy (DCS)	16 weeks

Collaborators and Investigators

• Sponsor: Drexel University
• Collaborators: University of Pennsylvania; Temple University
• Investigators: Principal Investigator: Peter A Lewin, PhD, Drexel University

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (ACTUAL): March 1, 2022
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (ESTIMATE): February 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: quality of life; therapeutic ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Varicose Veins; Diabetic Foot; Foot Ulcer; Ulcer; Varicose Ulcer
• Other Study ID Numbers: 1609004864

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED