Efficacy and Safety of 0.25% Timolol Gel in Enhancing Full Thickness Skin Grafts Healing and Cosmetic Outcomes: A Randomized, Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Evaluating the need for further scar revision (via dermabrasion or pulsed dye laser (PDL))
研究概览
简要总结
The use of topical beta-blockers, such as 0.25% timolol, in promoting wound healing is currently emerging in the academic literature. The investigators will enroll 82 patients who have their skin cancer surgically removed resulting in the need of a full-thickness skin graft. The objective of this randomized safety study is to determine the safety and efficacy of 0.25% timolol in promoting wound healing in full-thickness skin grafts compared to standard of care.
详细描述
The role of topical beta-blockers in promoting wound healing is currently emerging in the international literature. β2-Adrenergic receptors (B2AR) are the only subtype of beta-adrenoceptors expressed on skin. They can be found in secretory coil of apocrine glands, keratinocytes, fibroblasts and melanocytes. The distribution of these receptors provides insight on dermatological disorders that may be affected by β-blockers. Keratinocyte migration occurs by the facilitation of chemotaxis, the polarization of cells, and activation of extracellular signal-related kinases essential in the signaling of promigratory pathways. The B2AR activation inhibits keratinocyte migration by activating the serine/threonine phosphatase-2a, which downregulates phosphorylation of extracellular signal-related kinases necessary for migration. Therefore, B2AR antagonists prevent the phosphorylation of phosphatase-2a and have the downstream effect of extracellular signal-related kinase promotion, inducing a promigratory pathway in keratinocytes. Keratinocyte migration also occurs by galvanotaxis, a phenomenon in which cells migrate in response to electric stimuli. Keratinocytes can be stimulated to migrate with the formation of electrical poles and the application of electrical fields. The B2AR antagonists improve the ability of keratinocytes to respond to such migratory cues, whereas the B2AR agonists decrease keratinocytes' ability to respond, further implicating the use of topical timolol for recalcitrant wounds. Angiogenesis and dermal fibroblast proliferation are also regulated by B2ARs. The B2AR antagonists have been found to promote angiogenesis in chick chorioallantoic membrane assays and in vivo murine wound models. Dermal fibroblast migration is also increased (by 27%) when exposed to B2AR antagonists, and epidermal differentiation is improved with B2AR antagonists and β1- and β2-receptor antagonists.
Full-thickness skin grafts (FTSG) are one of the most commonly performed procedures in dermatologic, plastic and burn surgery. Various experimental approaches to optimize the healing of FTSG receiving sites have been described; however, no clearly superior and easily applicable method has gained wide acceptance in daily practice.
As indicated by preliminary evidence in other wound healing endeavors, 0.25% timolol gel may represent a commercially available, safe and simple, painless and relatively inexpensive treatment for improving healing of FTSG receiving site, as well as for improving cosmetic long term outcomes.
To assess the efficacy and safety of topically applied 0.25% timolol gel in promoting wound healing in FTSG receiving site versus standard of care (SOC) by:
- Evaluating healing in response to treatment with 0.25% topical timolol gel versus SOC in terms of wound surface area and Graft Take Score at the receiving site of a FTSG at 7 and 14 days;
- Evaluating cosmetic outcomes of the receiving site of a FTSG in terms of blinded physician (Vancouver Scar Scale, VSS) and patient (Visual Analogue Scale, VAS) assessment at 3 and 6 months' follow up;
- Evaluating the need for further scar revision (dermabrasion or pulsed dye laser [PDL]) at the 6-month follow up;
- Evaluating patient discomfort during the healing process by means of a patient pain VAS; and
- Determining the side effects associated with 0.25% timolol gel versus SOC
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Blinded physician will assess outcomes from pictures
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years of age
- •Undergoing a procedure which results in the need of a FTSG
- •Willing to provide written informed consent
排除标准
- •Age less than 18 years of age
- •Pregnant women
- •(Use of systemic drugs that can impede wound healing, such retinoids or immune-suppressive drugs)
- •Severe coagulation disorders
- •Severe, uncontrolled systemic comorbidities, such as diabetes, arthritis, etc.
- •Hypersensitivity to 0.25% timolol gel
- •Not willing to provide written informed consent
研究组 & 干预措施
0.25% Timolol gel applied to full-thickness skin graft
- During surgery: application of 0.25% timolol gel (2 drops per cm2) on wound bed before FTSG is placed
- During surgery: application of 0.25% timolol gel (2 drops per cm2) over FTSG after insetting of the graft
- After bolster removal (7 days): daily cleansing and daily 0.25% timolol (2 drops per cm2) application for 4 weeks
干预措施: 0.25% timolol gel with full-thickness skin grafts (Drug)
Standard of Care dressings
- FTSG surgery as per SOC
- After bolster removal (7 days): daily cleansing and daily Vaseline application for 4 weeks
干预措施: Vaseline dressing (Other)
结局指标
主要结局
Evaluating the need for further scar revision (via dermabrasion or pulsed dye laser (PDL))
时间窗: 6-months' post-surgery
A study physician will review the healed scar site to determine if there are potential cosmetic factors that could be improved through scar revision. If the patient is interested in having scar revision procedures, the study physician will offer a dermabrasion or PDL to treat the scar site.
次要结局
- Evaluating cosmetic outcomes of the receiving site of a FTSG via Vancouver Scar Scale (VSS)(3 months' post-surgery and 6 months' post-surgery)
- Evaluating change in healing response to treatment with 0.25% topical timolol gel versus SOC in terms of wound surface area at the receiving site of a FTSG via histogram planimetry(7 days post-surgery, and 14 days post-surgery)
- Evaluating cosmetic outcomes of the receiving site of a FTSG via patient Visual Analogue Scale (VAS)(3 months' post-surgery and 6 months' post-surgery)
- Evaluating change in healing response to treatment with 0.25% topical timolol gel versus SOC in terms of wound surface area at the receiving site of a FTSG via Graft Take Score(7 days post-surgery, and 14 days post-surgery)
- Evaluating change in patient discomfort during the healing process by means of a patient pain VAS(7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery)
- Determining change in the side effects associated with 0.25% timolol gel versus SOC via physician assessment(7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery)
- Determining change in the side effects associated with 0.25% timolol gel versus SOC via patient assessment(7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery)
研究者
Chrysalyne D Schmults, MD, MSCE
Director, Mohs and Dermatologic Surgery Center
Brigham and Women's Hospital