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Due to the insufficient accrual rate and strategic reasons to focus our efforts on higher impact research projects.
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.25% Timolol gel applied to full-thickness skin graft | Experimental |
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| Standard of Care dressings | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 0.25% timolol gel with full-thickness skin grafts | Drug | Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. |
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| Measure | Description | Time Frame |
|---|---|---|
| Healed Wound Surface in 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 | 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. | 7 days post-surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Successful (Completely Healed) Graft in Response to Treatment With 0.25% Topical Timolol Gel Versus SOC Using a Blinded Physician Assessment Score at the Receiving Site of a FTSG at 7 Days | 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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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mohs and Dermatologic Surgery Center, Brigham and Women's Hospital | Boston | Massachusetts | 02130 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.25% Timolol Gel Applied to Full-thickness Skin Graft |
0.25% timolol gel with full-thickness skin grafts: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 16, 2021 |
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The protocol will begin post-surgery. Eligible subjects will be assigned by computer-based randomization to case (0.25% timolol gel) or control (standard of care [SOC]) group and treated as follows:
Receiving site of FTSG/case group:
Receiving site of FTSG/control group:
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Blinded physician will assess outcomes from pictures
| Vaseline dressing | Other | Vaseline will be applied to wound bed immediately after surgery before dressing is applied. |
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| 7 days post-surgery |
| Patient Discomfort During the Healing Process by Means of a Patient Pain VAS | 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. The score ranges from 1 to 10. A lower score is considered to have a better outcome and a higher score is considered a worse outcome. | 7 days' post-surgery |
| Number of Participants With Side Effects Associated With 0.25% Timolol Gel Versus SOC Via Physician Assessment | 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. | 7 days' post-surgery |
| Number of Participants With Side Effects Associated With 0.25% Timolol Gel Versus SOC Via Patient Assessment | Patients will report any side effects they experience post-surgery | 7 days' post-surgery |
| FG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 0.25% Timolol Gel Applied to Full-thickness Skin Graft |
0.25% timolol gel with full-thickness skin grafts: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. |
| BG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | 1 participant withdrew from study | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Healed Wound Surface in 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 | 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. | Data not collected per histoplanimetry method of analysis due to the absence of a required calibration reference at the time of image capture. Histoplanimetry relies on accurate calibration to ensure that measurements taken from the wound images are consistent, reliable, and reproducible. Data is not available now nor will it be available in the future. | Posted | Count of Participants | Participants | 7 days post-surgery |
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| Secondary | Rate of Successful (Completely Healed) Graft in Response to Treatment With 0.25% Topical Timolol Gel Versus SOC Using a Blinded Physician Assessment Score at the Receiving Site of a FTSG at 7 Days | 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. | Posted | Mean | Standard Deviation | score on a scale | 7 days post-surgery |
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| Secondary | Patient Discomfort During the Healing Process by Means of a Patient Pain VAS | 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. The score ranges from 1 to 10. A lower score is considered to have a better outcome and a higher score is considered a worse outcome. | Posted | Mean | Standard Deviation | score on a scale | 7 days' post-surgery |
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| Secondary | Number of Participants With Side Effects Associated With 0.25% Timolol Gel Versus SOC Via Physician Assessment | 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. | Posted | Count of Participants | Participants | 7 days' post-surgery |
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| Secondary | Number of Participants With Side Effects Associated With 0.25% Timolol Gel Versus SOC Via Patient Assessment | Patients will report any side effects they experience post-surgery | Posted | Count of Participants | Participants | 7 days' post-surgery |
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over 7 days, the duration of the study
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.25% Timolol Gel Applied to Full-thickness Skin Graft |
0.25% timolol gel with full-thickness skin grafts: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. | 0 | 3 | 0 | 3 | 0 | 3 |
| EG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. | 0 | 5 | 0 | 5 | 0 | 5 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BWH Dermatology Research Project Coordinator | Brigham and Women's Hospital | 617-264-5696 | lchacin@bwh.harvard.edu |
| Mar 18, 2026 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 18, 2021 | Mar 18, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000072836 | Surgical Wound |
| ID | Term |
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| D014947 | Wounds and Injuries |
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