Topical 0.5% Timolol Solution for Healing Lower Extremity Wounds

Efficacy of Topical 0.5% Timolol Solution for Healing Lower Extremity Wounds

Topical timolol, a β2-Adrenergic receptor (B2AR) antagonist, has demonstrated promise in wound healing over the past several years. The majority of the literature has evaluated the use of topical timolol to shorten wound healing time in chronic wounds of non-surgical etiologies. To date, there are no prospective randomized clinical trials evaluating the role of topical timolol for shortening wound healing time in acute open surgical wounds.

Therefore, the purpose of this study is to determine whether or not topical timolol solution decreases time to wound healing in patients with defects after Mohs Micrographic Surgery (MMS) that cannot be closed with sutures and are left to heal by second intent. The research team also will look to determine if there is a difference in cosmesis of wounds treated with topical timolol compared to those treated with the standard of care. The present study will primarily focus on wounds in the distal lower extremity as these are most commonly left to heal by secondary intent

Study Overview

• Status: Recruiting
• Conditions: Wound Healing; Mohs Micrographic Surgery
• Intervention / Treatment: Drug: Timolol Maleate Solution; Other: Standard of Care

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jesse Lewin, MD; Phone Number: 212-731-3316; Email: jesse.lewin@mountsinai.org
• Study Contact Backup: Name: Jaclyn Himeles, MD; Phone Number: 212-731-3316; Email: jaclyn.himeles@Mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10028
      • Recruiting
      • Mount Sinai
      • Contact: Jesse Lewin, MD; Phone Number: 212-731-3316; Email: jesse.lewin@mountsinai.org
      • Contact: Jaclyn Himeles, MD; Phone Number: 212-731-3316; Email: jaclyn.himeles@Mountsinai.org
      • Contact: Jesse Lewin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be scheduled to undergo MMS at 234 East 85th St for a skin cancer that is deemed Mohs
• Appropriate by the Mohs surgery appropriate use criteria
• Have an open surgical wound < 4 cm and > 0.5 cm
• Be ≥18 years of age
• English-speaking
• Provide a signed and dated informed consent form
• State willingness to comply with all study procedures

Exclusion Criteria:

• Age less than 18 years of age
• Open surgical wound > 4 cm
• If tumor clearance cannot be achieved with MMS
• Pregnant women
• Breastfeeding women
• Patients who are taking oral beta-blockers (ie oral timolol, metoprolol, carvedilol, propranolol, atenolol)
• Patients who are currently taking any of the following medications: clonidine, digoxin, methyldopa, quinidine, fluoxetine and paroxetine, bupropion
• Patient currently taking a calcium channel blocker AND has pre-existing heart failure as defined by a reduced ejection fraction
• Patients with pre-existing hypotension
• Pre-existing diagnosis of sinus bradycardia
• Pre-existing diagnosis of second or third degree atrioventricular block
• Congestive heart failure
• Pre-existing diagnosis of severe asthma
• Pre-existing diagnosis of chronic obstructive pulmonary disease
• Any known hypersensitivity to 0.5% timolol solution
• Patients who have a wound where primary closure is feasible and desired by the patient
• Defect size <0.5 cm
• Prior sensitivity or known allergy to timolol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Timolol; Participants in the topical timolol group will be instructed to apply 1-3 drops of topical 0.5% timolol solution daily to the wound.	Drug: Timolol Maleate Solution; Timolol 0.5% solution. The number of drops delivered will be based on the initial wound size and will remain constant for the duration of the study period or until the wound is fully re-epithelialized which will be determined by the PI either by photo or in person visit.
Active Comparator: Standard of Care; Standard of Care - Apply Vaseline and Band-Aid to wound bed daily	Other: Standard of Care; Vaseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound surface area healing (skin reepithelialization)	The wound surface area healing (skin reepithelialization) in open post-surgical lower extremity wounds will be measured using a ruler.	2 weeks, 4 weeks, 6 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in surgical wound size	Percentage change in surgical wound size	2 weeks, 4 weeks, 6 weeks, 12 weeks
Modified Manchester Scar Scale (MMSS)	The Modified Manchester Scar Scale (MMSS) is a clinical tool used to evaluate the appearance and characteristics of scars. The MMSS assess four key aspects of the scar: Color (compared to surrounding skin): Rated 1-4Perfect match (1) to gross mismatch (4); Matte vs. Shine: Rated 1-2Matte appearance (1)Shiny appearance (2); Contour: Rated 1-3Flush with surrounding skin (1)Slightly proud/indented (2)Hypertrophic (3); Distortion: Rated 1-4No distortion (1 point) to severe distortion (4 points) The total score ranges from 4 to 13, with higher scores indicating a more noticeable or problematic scar.	2 weeks, 4 weeks, 6 weeks, 12 weeks
The Pain, Enjoyment of Life and General Activity scale (PEG)	The PEG, a Three-item Scale Assessing Pain Intensity and Interference Pain is is a 3-item questionnaire that measures pain intensity and pain-related functional interference with open wounds on the lower leg. The assessment includes three domains: average pain intensity (0-10), pain interference with enjoyment of life (0-10), and pain interference with general activity (0-10). The total score ranges from 0-30, with higher scores indicating greater pain intensity and greater pain-related functional interference.	2 weeks, 4 weeks, 6 weeks, 12 weeks
Wound Quality of Life Questionnaire (Wound-QOL)	The Wound-QoL is a17-item questionnaire assesses how patients feel about their open wound its impact on their quality of life. The assessment evaluates multiple dimensions of wound-related quality of life, including physical symptoms (items 1-3), functional limitations (items 4, 11-15), psychological well-being (items 6-10), and burden of care (items 5, 16-17). Each item is scored on a 5-point scale from "Not at all" (0) to "Very much" (4). The total score ranges from 0-68, with higher scores indicating lower wound quality of life.	2 weeks, 4 weeks, 6 weeks, 12 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Jesse Lewin, MD, Primary Investigator

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2025
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adrenergic Agents; Antihypertensive Agents; Adrenergic beta-Antagonists; Adrenergic Antagonists; Timolol
• Other Study ID Numbers: STUDY-23-01193

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose.

To achieve aims in the approved proposal.

Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in ISMMS data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (to be determined).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes