Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 114 patients who have their skin cancer surgically removed resulting in open surgical wounds less or equal to 1.5 cm. The objective of this randomized safety study is to determine the safety and efficacy of 0.25% timolol in promoting wound healing in open surgical wounds less or equal to 1.5 cm.
Healing of a cutaneous defect by second intention is a complex process. Migration of fibroblasts, keratinocytes, and other cell types to the site of defect and their proliferation under stimulation by cytokines and growth factors occur during this process. The role of topical beta-blockers in promoting wound healing is currently emerging in the international literature (1-3). β2-Adrenergic receptors (B2AR) are the only subtype of beta-adrenoceptors expressed on skin (4-6). 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 (4-6). 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 (4-6). 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 (5-10).
Topical beta-blockers have been gaining increasing popularity and evidence over the last few years as enhancers of wound healing in acute and chronic open wounds. In particular, 0.25% timolol gel may represent a commercially available, safe and simple, painless-though perhaps moderately expensive-treatment for improving both acute and chronic open wounds, as well as for improving long-term cosmetic outcomes.
To assess the efficacy and safety of topically applied 0.25% timolol gel in promoting wound healing in surgical open wounds ≤1.5cm versus standard of care (SOC) by:
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.25% Timolol gel under the paraffin gauzes | Experimental |
|
|
| Standard of Care dressings | Active Comparator |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 0.25% Timolol gel with paraffin gauze dressings | Drug | Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply 0.25% topical timolol gel (1 drop = 0.1ml for each cm2 of wound area), and re-cover wound with clean dressing |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Re-epithelialization at 30 Days Post op | Evaluating the difference in wound re-epithelialization at 30 days after surgery between the groups. Re-epithelialization (yes vs. no) will be evaluated by 2 independent investigators. | 30 days' post-surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Cosmetic Outcomes of Open Surgical Wound Healing by Blinded Physician Vancouver Scar Scale Assessment | A physician blinded to the treatment group the subject is in will self-administer the Vancouver Scar Scale (VSS) which documents change in scar appearance over time via standardized photographs. The VSS ranges from 0 (most desirable outcome) to 13 (least desirable outcome), thus, a lower score is considered to have a better outcome and a higher score is considered a worse outcome. The VSS consists of four sub-scales, with each sub-scale reporting a value. The "pigmentation sub-scale" ranges from 0 (normal pigmentation) to 2 (hyperpigmentation); the "vascularity sub-scale" ranges from 0 (normal appearance) to 3 (purple appearance); the "pliability sub-scale" ranges from 0 (normal pliability) to 5 (contracture); and the "height sub-scale" ranges from 0 (normal [flat]) to 3 (>5mm). Sub-scale scores are combined to give an overall VSS assessment score. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Chrysalyne D Schmults, MD, MSCE | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mohs and Dermatologic Surgery Center, Brigham and Women's Hospital | Boston | Massachusetts | 02130 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24172892 | Background | Braun LR, Lamel SA, Richmond NA, Kirsner RS. Topical timolol for recalcitrant wounds. JAMA Dermatol. 2013 Dec;149(12):1400-2. doi: 10.1001/jamadermatol.2013.7135. No abstract available. | |
| 25936635 | Background | Ali A, Herndon DN, Mamachen A, Hasan S, Andersen CR, Grogans RJ, Brewer JL, Lee JO, Heffernan J, Suman OE, Finnerty CC. Propranolol attenuates hemorrhage and accelerates wound healing in severely burned adults. Crit Care. 2015 May 4;19(1):217. doi: 10.1186/s13054-015-0913-x. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 0.25% Timolol Gel Under the Paraffin Gauzes |
0.25% Timolol gel with paraffin gauze dressings: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply 0.25% topical timolol gel (1 drop = 0.1ml for each cm2 of wound area), and re-cover wound with clean dressing |
| FG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply Vaseline, and re-cover wound with clean dressing |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 0.25% Timolol Gel Under the Paraffin Gauzes |
0.25% Timolol gel with paraffin gauze dressings: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply 0.25% topical timolol gel (1 drop = 0.1ml for each cm2 of wound area), and re-cover wound with clean dressing |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 14 patients were lost to follow up, did not apply the drug/control. After attempts of contacting them, they still did not send pictures, implying withdrawal from study. Subjects tend to neglect their follow up appointments if they have no active complaints. As most of the wounds heal without complications, some subjects may not feel the importance of follow ups. 2 were found ineligible 4 withdrew consent |
| 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 | Number of Participants With Re-epithelialization at 30 Days Post op | Evaluating the difference in wound re-epithelialization at 30 days after surgery between the groups. Re-epithelialization (yes vs. no) will be evaluated by 2 independent investigators. | The timolol group enrolled 44, but 9 were excluded from analysis because subjects did not provide pictures at 30 days. The control group enrolled 43, but 5 were excluded from analysis because subjects did not provide pictures at 30 days | Posted | Number | participants | 30 days' post-surgery |
|
6 months
Not provided
Not provided
| 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 Under the Paraffin Gauzes |
0.25% Timolol gel with paraffin gauze dressings: Timolol 0.25% gel will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply 0.25% topical timolol gel (1 drop = 0.1ml for each cm2 of wound area), and re-cover wound with clean dressing |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Temporary tinnitus, nausea and headache | Nervous system disorders | Non-systematic Assessment | Patient developed tinnitus, nausea and headache for 3 days which she attributed to Timolol. Patient had no other symptoms. Patient became asymptomatic after stopping Timolol and remained asymptomatic afterwards. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Chrysalyne Schmults | Brigham and Women's hospital | 61798374626 | cschmults@bwh.harvard.edu |
Not provided
| 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 | Nov 17, 2019 | Jan 7, 2026 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 13, 2019 | Jan 7, 2026 | ICF_002.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000072836 | Surgical Wound |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
Not provided
Not provided
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:
Case group:
SOC group:
Not provided
Not provided
Blinded physician will assess outcomes from pictures
|
| Vaseline dressing | Other | Vaseline will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply Vaseline, and re-cover wound with clean dressing |
|
| 3 months' post-surgery |
| Study Subject Complete the Patient Scar Assessment Via Visual Analogue Scale | 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. The score ranges from 1 (no complaints with how scar appears cosmetically to normal skin) to 10 (worst imaginable scar compared to normal skin). A lower score is considered to have a better outcome and a higher score is considered a worse outcome. | 6 months' post-surgery |
| Number of Participants Whose Side Effects Are Associated With 0.25% Topical Timolol for Open Surgical Wounds | Patients will report and side effects they experience post-surgery. A physician will also 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. | Up to 6 months' post-surgery |
| 26800510 | Background | Vestita M, Bonamonte D, Filoni A. Topical propranolol for a chronic recalcitrant wound. Dermatol Ther. 2016 May;29(3):148-9. doi: 10.1111/dth.12328. Epub 2016 Jan 22. No abstract available. |
| 27701128 | Background | Yesiloglu N, Yildiz K, Cem Akpinar A, Gorgulu T, Sirinoglu H, Ozcan A. Histogram Planimetry Method for the Measurement of Irregular Wounds. Wounds. 2016 Sep;28(9):328-333. |
| 29037357 | Background | Thomas B, Kurien JS, Jose T, Ulahannan SE, Varghese SA. Topical timolol promotes healing of chronic leg ulcer. J Vasc Surg Venous Lymphat Disord. 2017 Nov;5(6):844-850. doi: 10.1016/j.jvsv.2017.04.019. Epub 2017 Aug 7. |
| 24438420 | Background | Manahan MN, Peters P, Scuderi S, Surjana D, Beardmore GL. Topical timolol for a chronic ulcer--a case with its own control. Med J Aust. 2014 Jan 20;200(1):49-50. doi: 10.5694/mja13.10823. No abstract available. |
| 24034405 | Background | Lev-Tov H, Dahle S, Moss J, Isseroff RR. Successful treatment of a chronic venous leg ulcer using a topical beta-blocker. J Am Acad Dermatol. 2013 Oct;69(4):e204-5. doi: 10.1016/j.jaad.2013.06.003. No abstract available. |
| 22093053 | Background | Tang JC, Dosal J, Kirsner RS. Topical timolol for a refractory wound. Dermatol Surg. 2012 Jan;38(1):135-8. doi: 10.1111/j.1524-4725.2011.02200.x. Epub 2011 Oct 31. No abstract available. |
| 28494521 | Background | Zheng Z, Liu Y, Yang Y, Tang J, Cheng B. Topical 1% propranolol cream promotes cutaneous wound healing in spontaneously diabetic mice. Wound Repair Regen. 2017 May;25(3):389-397. doi: 10.1111/wrr.12546. Epub 2017 May 26. |
| Physician Decision |
|
| BG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply Vaseline, and re-cover wound with clean dressing |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply Vaseline, and re-cover wound with clean dressing |
|
|
|
| Secondary | Cosmetic Outcomes of Open Surgical Wound Healing by Blinded Physician Vancouver Scar Scale Assessment | A physician blinded to the treatment group the subject is in will self-administer the Vancouver Scar Scale (VSS) which documents change in scar appearance over time via standardized photographs. The VSS ranges from 0 (most desirable outcome) to 13 (least desirable outcome), thus, a lower score is considered to have a better outcome and a higher score is considered a worse outcome. The VSS consists of four sub-scales, with each sub-scale reporting a value. The "pigmentation sub-scale" ranges from 0 (normal pigmentation) to 2 (hyperpigmentation); the "vascularity sub-scale" ranges from 0 (normal appearance) to 3 (purple appearance); the "pliability sub-scale" ranges from 0 (normal pliability) to 5 (contracture); and the "height sub-scale" ranges from 0 (normal [flat]) to 3 (>5mm). Sub-scale scores are combined to give an overall VSS assessment score. | Posted | Mean | Standard Deviation | score on a scale | 3 months' post-surgery |
|
|
|
| Secondary | Study Subject Complete the Patient Scar Assessment Via Visual Analogue Scale | 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. The score ranges from 1 (no complaints with how scar appears cosmetically to normal skin) to 10 (worst imaginable scar compared to normal skin). 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 | 6 months' post-surgery |
|
|
|
| Secondary | Number of Participants Whose Side Effects Are Associated With 0.25% Topical Timolol for Open Surgical Wounds | Patients will report and side effects they experience post-surgery. A physician will also 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 | Up to 6 months' post-surgery |
|
|
|
| 0 |
| 44 |
| 0 |
| 44 |
| 1 |
| 44 |
| EG001 | Standard of Care Dressings |
Vaseline dressing: Vaseline will be applied to wound bed immediately after surgery before dressing is applied. Starting the day after surgery: each day, the patient will cleanse the surgical site, apply Vaseline, and re-cover wound with clean dressing | 0 | 43 | 0 | 43 | 0 | 43 |
|
Not provided
Not provided