- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03579160
Efficacy and Safety of 0.25% Timolol Gel in Enhancing Full Thickness Skin Grafts Healing and Cosmetic Outcomes (FTSG)
Efficacy and Safety of 0.25% Timolol Gel in Enhancing Full Thickness Skin Grafts Healing and Cosmetic Outcomes: A Randomized, Controlled Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02130
- Mohs and Dermatologic Surgery Center, Brigham and Women's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years of age
- Undergoing a procedure which results in the need of a FTSG
- Willing to provide written informed consent
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 0.25% Timolol gel applied to full-thickness skin graft
|
Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied.
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ACTIVE_COMPARATOR: Standard of Care dressings
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Vaseline will be applied to wound bed immediately after surgery before dressing is applied.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluating the need for further scar revision (via dermabrasion or pulsed dye laser (PDL))
Time Frame: 6-months' post-surgery
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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.
|
6-months' post-surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluating cosmetic outcomes of the receiving site of a FTSG via Vancouver Scar Scale (VSS)
Time Frame: 3 months' post-surgery and 6 months' post-surgery
|
Physician blinded to subject's treatment group uses VSS which documents scar appearance change over time via photos.
VSS ranges from 0 (most desirable outcome) to 13 (least desirable).
A lower score is considered a better outcome and a higher score is a worse outcome.
VSS consists of 4 sub-scales, with each reporting a value.
The "pigmentation" ranges from 0 (normal pigment) to 2 (hyperpigment); "vascularity" ranges from 0 (normal appearance) to 3 (purple appearance); "pliability" ranges from 0 (normal) to 5 (contracture); "height" ranges from 0 (normal/flat) to 3 (>5mm).
Sub-scale scores are combined to give an overall VSS score.
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3 months' post-surgery and 6 months' post-surgery
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Evaluating cosmetic outcomes of the receiving site of a FTSG via patient Visual Analogue Scale (VAS)
Time Frame: 3 months' post-surgery and 6 months' post-surgery
|
Scar VAS rates subjects' graft cosmetic appearance.
Each question ranges from 1 (no complaints w/ itch or pain/as normal skin) to 10 (worst imaginable itch or pain/very different from normal skin).
Ranges from 6 (best outcome score) to 66 (worst outcome score); a lower score is considered a better outcome and a higher score is considered a worse outcome.
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3 months' post-surgery and 6 months' post-surgery
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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
Time Frame: 7 days post-surgery, and 14 days post-surgery
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The Graft Take Score will be used to assess amount of graft take at each visit.
Graft take is considered "Good" if 90%+ of the graft site is healed and pink/purple in color; "Moderate" if there is 50% healing, pink or purple in color, and >50% of the graft has taken; and "Poor" if <50% graft take.
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7 days post-surgery, and 14 days post-surgery
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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
Time Frame: 7 days post-surgery, and 14 days post-surgery
|
Histogram planimetry is more accessible than automated analysis software programs, and it is based on the pixel count of a selected irregular area which is divided by the pixel count of 1 cm2 to find a result in terms of cm2 or mm2.
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7 days post-surgery, and 14 days post-surgery
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Evaluating change in patient discomfort during the healing process by means of a patient pain VAS
Time Frame: 7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery
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Subjects will be asked to complete a Visual Analogue Scale for scar assessment to rate how they think their graft sites appear cosmetically compared to normal skin, and any complaints about how painful they sites are, and how itchy they feel.
Each question ranges from 1 (no complaints with itch or pain/as normal skin) to 10 (worst imaginable itch or pain/very different from normal skin).
The score ranges from 6 (best outcome score) to 66 (worst outcome score), thus a lower score is considered to have a better outcome and a higher score is considered a worse outcome.
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7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery
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Determining change in the side effects associated with 0.25% timolol gel versus SOC via physician assessment
Time Frame: 7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery
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A physician will assess for side effects and determine whether they are likely associated with the 0.25% topical timolol or part of the normal wound healing experience.
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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
Time Frame: 7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery
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Patients will report any side effects they experience post-surgery
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7 days' post-surgery, 14 days' post-surgery, 30 days' post-surgery, 3 months' post-surgery, 6 months' post-surgery
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Wounds and Injuries
- Surgical Wound
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Dermatologic Agents
- Emollients
- Timolol
- Petrolatum
Other Study ID Numbers
- BWHMDSC003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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