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

• ClinicalTrials.gov Identifier: NCT03041844
• Recruitment Status: Recruiting
• First Posted: February 3, 2017
• Last Update Posted: July 24, 2020
• Sponsor: Drexel University
• Collaborators: University of Pennsylvania; Temple University
• Information provided by (Responsible Party): Drexel University

Tracking Information

• First Submitted Date: January 25, 2017
• First Posted Date: February 3, 2017
• Last Update Posted Date: July 24, 2020
• Study Start Date: January 2017
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 1, 2017)

Change in wound size [ Time Frame: 4 weeks ]

Percentage change in wound size over 4 weeks

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 20, 2018)

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

Original Secondary Outcome Measures (submitted: February 1, 2017)

• Wound closure [ Time Frame: 16 weeks ]
  Complete wound closure at 16 weeks
• Health Related Quality of Life (HRQOL) [ Time Frame: 16 weeks ]
  Short form health survey will be administered to assess changes in HRQOL
• Wound Quality of Life (WQOL) [ Time Frame: 16 weeks ]
  Health survey will be administered to assess changes in wound-related HRQOL
• Wound oxyhemoglobin concentration change [ Time Frame: 16 weeks ]
  Change in wound oxyhemoglobin concentration per week, measured with diffuse near infrared spectroscopy (DNIRS)
• Microcirculatory blood flow index change [ Time Frame: 16 weeks ]
  Change in microcirculatory blood flow index per week, measured with diffuse correlation spectroscopy (DCS)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Enhanced Ultrasound Treatment of Chronic Wounds With Monitoring of Healing and Quality of Life Outcomes
• Official Title: Not Provided
• Brief Summary: 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Diabetic Foot Ulcer
• Venous Ulcer

Intervention

• Device: Low Frequency, Low Intensity Ultrasound
  Therapeutic ultrasound (20 kHz, <100 mW/cm2 spatial peak-temporal peak)
• Device: Sham Applicator
  Sham ultrasound applicator

Study Arms

• Experimental: Low Frequency, Low Intensity Ultrasound
  Low Frequency, Low Intensity therapeutic ultrasound applied weekly for up to 16 weeks.
  Intervention: Device: Low Frequency, Low Intensity Ultrasound
• Sham Comparator: Sham Ultrasound
  Sham ultrasound applied weekly for up to 16 weeks.
  Intervention: Device: Sham Applicator

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 1, 2017): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Michael S Weingarten, MD; 215-762-7008; Michael.Weingarten@drexelmed.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03041844
• Other Study ID Numbers: 1609004864
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Drexel University
• Study Sponsor: Drexel University

Collaborators

• University of Pennsylvania
• Temple University

Investigators

• Principal Investigator: Peter A Lewin, PhD; Drexel University

• PRS Account: Drexel University
• Verification Date: July 2020