COMS for Chronic Ulcers Treatment
NCT Number: NCT06528873
Acronym: NAZARÉ
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Venous Leg Ulcer|Wound Heal|Magnetic Field Exposure
Interventions: COMBINATION_PRODUCT: Concurrent optical and magnetic stimulation (COMS) treatment
Sponsor: Sebastian Probst
Collaborators: Medical University of Vienna|University Hospital, Geneva|Medical Centre Cité Générations|Jura Hospital|Clinique des Augustines|Venenklinik Bellevue|UniversitÃ¤tsklinikum Hamburg-Eppendorf|Medical University of Graz|UniversitÃ¤t Duisburg-Essen|University Hospital, ZÃ¼rich|Hospital Thun
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 122
Study Design: Allocation: RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: DEVICE_FEASIBILITY
Start Date: 2024-10-01
Completion Date: 2026-09-30

Summary:
Chronic leg and foot ulcers are defined as wounds that fail to heal in a timely manner, typically persisting for over 4 to 8 weeks without substantial healing despite standard care. These ulcers often result from macro- and microvascular disorders, the most common being chronic venous insufficiency (CVI), alone or with peripheral artery disease (PAD) or microangiopathy. Despite different causes, chronic vascular-origin wounds share similar biological traits and require the same physiological processes for healing.

Vascular issues hinder blood perfusion, reducing oxygen, nutrients, and growth factors, leading to decreased energy metabolism and impaired cell functions necessary for proliferation, extracellular matrix production, angiogenesis, and tissue regeneration. Reduced blood supply also limits leukocyte function, compromising the immune response and leading to persistent inflammation and infection. Consequently, these wounds cannot effectively heal, showing prolonged inflammation, persistent infections, and cellular senescence.

Best practice wound care includes compression therapy and physical activity for venous ulcers, and angioplasty, surgery, or bypass for arterial ulcers. These treatments aim to improve blood flow, reduce venous stasis, and enhance venous return. Compression therapy and physical activity lower hydrostatic pressure in the lower limb, while angioplasty and surgery remove arterial blockages or create new blood flow routes.

Recent studies highlight the role of mechano-sensitive (MS) ion channels in skin cell processes and their dysfunction in dermatological disorders. Magnetic stimulation can activate MS TRCP1 channels, enhancing mitochondrial respiration and mitochondriogenesis via the Ca2+/CalModulin(CaM)/NFAT/PGC-1α pathway. Ca2+-activated calmodulin also catalyzes nitric oxide (NO), promoting vasodilation and tissue perfusion.

Bimodal red and near-infrared photobiomodulation can further increase mitochondrial respiration and ATP production by activating Cytochrome C oxidase and mitigating NO-induced downregulation. This synergistic mechanism of concurrent optical and magnetic stimulation (COMS) may amplify Ca2+ and NO-mediated processes like cell proliferation, migration, vasodilation, and angiogenesis while resolving inflammation. Thus, COMS may offer a promising therapy for chronic, inflammation-prone wounds.

The effectiveness of COMS has yet to be validated in large-scale studies. This proposal aims to assess the impact of COMS therapy combined with standard care versus standard care alone on healing, wound closure, recurrence, pain, quality of life, economic outcomes, and device usability in patients with venous leg ulcers (VLU) and VLU associated with PAD in a large-scale multicentric randomized controlled trial.

Primary Outcome Measures: Percent wound area reduction, Percent wound area reduction (PWAR) at week 12 will be measured from pictures of the wound taken with ImitoWound research application. PWAR is computed as (Wound area at baseline - Wound area at 12 weeks) / Wound area at baseline.

The picture of the wound will be taken after dressing removal, wound debridement (if applicable) and wound cleansing. ImitoWound research App will be used in a smartphone as instructed in supplier's wound imaging and measurement guidelines. The camera of the smartphone will be positioned 20 to 30 cm away from and parallel to the wound. A calibration marker (quick response \[QR\] code) will be positioned next to and in the same plane of the wound, and a photograph will be taken after recognition of the QR code by the Imito App, automatic wound measurement will take place. Study nurses will receive concise training and document with step-by-step procedure for how to use Imito App., 24 weeks