Venous Ulcers and Hyaluronic Acid Phonophoresis

NCT07626203 | Completed

• 1 other identifier: Hyaluronic acid phonophoresis
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Venous leg ulcers are severe manifestations of chronic venous insufficiency and account for a large proportion of lower limb ulcers. They typically occur below the knee, persist for more than six weeks, and are associated with significant impairment in quality of life and substantial socioeconomic burden. A major clinical challenge is their high recurrence rate, which can reach 50-70% within six months, making treatment resource-intensive and requiring multidisciplinary care. Therapeutic ultrasound and phonophoresis have been proposed to enhance wound healing by promoting tissue repair and improving transdermal drug delivery, including hyaluronic acid, which supports extracellular matrix restoration and wound healing. However, despite the theoretical advantages of combining ultrasound with hyaluronic acid, robust clinical evidence for its effectiveness in venous leg ulcers remains limited. The study aimed to assess the effect of ultrasound-enhanced hyaluronic acid delivery on venous ulcer healing compared to ultrasound followed by topical application of hyaluronic acid.

Conditions

Venous Ulcer; Venous Ulcer of Leg

Keywords

hyaluronic acid; ultrasound; phonophoresis; venous ulcer

Outcome Measures

Primary Outcomes (1)

• Percentage Wound Area Reduction (PWAR)

  It is calculated as: \[(baseline wound area - post-treatment wound area) ÷ baseline wound area\] × 100. Digital wound measurements were obtained at baseline and at week four using the validated imitoMeasure smartphone application (imito AG, Zurich, Switzerland). Standardized image acquisition procedures were followed, with the smartphone camera positioned 20-30 cm from the wound and maintained parallel to the wound surface. A calibration marker (QR code) was placed adjacent to the wound on the same plane before image capture, and a photo was taken once the app recognized the QR code. The operator delineated the wound borders on the photo using their finger then the app generated measurements of area, width, length, and circumference.

  After 3 sessions per week for 4 weeks

Secondary Outcomes (1)

• Rate of Healing

  After 3 sessions per week for 4 weeks

Study Arms (2)

Study Group A

EXPERIMENTAL

This group included 32 patients with venous ulcers who received combined treatment of topical hyaluronic acid gel and therapeutic ultrasound therapy, three sessions weekly for four weeks, in addition to the traditional physical therapy management including compression therapy and active ankle exercises.

Other: Phonophoresis group (A)

Study Group B

EXPERIMENTAL

This group included 32 patients with venous ulcers who received ultrasound first then followed by topical hyaluronic acid, three sessions weekly for four weeks in addition to the traditional physical therapy management including compression therapy and active ankle exercises.

Other: Ultrasound-preceded gel (hyaluronic acid gel) group (B):

Interventions

Phonophoresis group (A) OTHER

For Study Group (A): A layer of 0.2% topical hyaluronic acid gel was applied to cover and fill the wound cavity . A sterile glove filled with ultrasound gel was, then secured to the wound with surgical plaster, and ultrasound therapy was applied concurrently. The ultrasound was delivered for 1 minute per 1 cm² of the wound. The parameters used were 0.5 W/cm², low intensity, 1 MHz frequency, and pulsed mode with a 20% duty cycle, adjusted based on the ulcer size. The gel was removed, and the wound was dried and cleaned with saline and the US head with alcohol after each session. The treatment period lasted 4 weeks, with three sessions per week.

Study Group A

Ultrasound-preceded gel (hyaluronic acid gel) group (B): OTHER

Pulsed TUS was applied to the wound area at identical parameters to Group A (0.5 W/cm², 1 MHz, 20% duty cycle, one minute per cm²). Immediately following the TUS session, 0.2% HA gel was applied topically to the wound surface. Standard wound care was delivered as described for Group A. Treatment frequency and duration were identical to Group A.

Study Group B

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both genders whose ages were between 30 - 70 years.
• Patients with active venous ulcers (C6) according to CEAP (Clinical manifestations- Etiology- Anatomic distribution-Pathophysiology) classification.
• clinically proved to be non-infected venous ulcers.
• Patients receive the traditional physical therapy management for venous ulcers which includes compression therapy and active exercise plus frequent dressing change.
• Patients suffering from recurrent or failed to heal venous ulcers.

You may not qualify if:

• Individuals who were confined to bed with life-threatening conditions that could interfere with the study's objectives, such as myocardial infarction, renal failure or autoimmune diseases.
• Patients who had hyaluronic acid hypersensitivity.
• Presence of skin disorders or conditions that considered contraindicated for therapeutic US (e.g., cellulitis).

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Outpatient Clinics of Faculty of Physical Therapy ,Cairo University.

Giza, Egypt

Location

Related Publications (5)

• https://www.mdpi.com/2077-0383/11/3/537

  BACKGROUND

• https://www.mdpi.com/2073-4409/11/15/2439

  BACKGROUND

• Alkahtani SA, Kunwar PS, Jalilifar M, Rashidi S, Yadollahpour A. Ultrasound-based Techniques as Alternative Treatments for Chronic Wounds: A Comprehensive Review of Clinical Applications. Cureus. 2017 Dec 15;9(12):e1952. doi: 10.7759/cureus.1952.

  PMID: 29487767 BACKGROUND

• Biagioni RB, Carvalho BV, Manzioni R, Matielo MF, Brochado Neto FC, Sacilotto R. Smartphone application for wound area measurement in clinical practice. J Vasc Surg Cases Innov Tech. 2021 Feb 26;7(2):258-261. doi: 10.1016/j.jvscit.2021.02.008. eCollection 2021 Jun.

  PMID: 33997567 BACKGROUND

• Raffetto JD, Ligi D, Maniscalco R, Khalil RA, Mannello F. Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment. J Clin Med. 2020 Dec 24;10(1):29. doi: 10.3390/jcm10010029.

  PMID: 33374372 BACKGROUND

MeSH Terms

Conditions

Varicose Ulcer

Interventions

Population Groups

Condition Hierarchy (Ancestors)

Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• HESHAM GALAL MAHRAN, Professor of PT

  Faculty of Physical Therapy, department of physical therapy for surgery, Cairo University, Egypt

  STUDY DIRECTOR

• SHAIMAA MOHAMED ELSAYEH, Ass. Prof. of PT

  Faculty of Physical Therapy, department of physical therapy for surgery, Cairo University, Egypt

  STUDY DIRECTOR

• WALIED MOHAMED KHEREBA, Prof. vascular surgery

  Faculty of medicine, department of vascular and endovascular surgery, AL-Azhar University New Damietta, Egypt

  STUDY DIRECTOR

• Rasha S Farag, MSc

  Damietta Directorate for Health Affairs

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Master of Physical Therapy for Surgery, Cairo University, Egypt

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 4, 2026
• Study Start: December 12, 2024
• Primary Completion: February 20, 2025
• Study Completion: February 26, 2025
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)