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Timolol for the Treatment of Acne and Rosacea

Primary Purpose

Acne Vulgaris, Rosacea

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Timolol
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acne Vulgaris focused on measuring Acne vulgaris, Rosacea

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • In the opinion of the investigator, must be medically able to undergo the administration of study material
  • Be able to comprehend the informed consent document and provide consent for participation

  • Females of childbearing potential must:

    • Not be pregnant by subjective report
    • agree to not become pregnant or breastfeed for the period of the study through 1 month after completion of the study
    • be willing to use a reliable form of contraception during the study
  • Be willing and able to comply with the scheduled visits and other study procedures for the duration of the study.
  • Be willing not to take any other medicine for acne or rosacea during the study

  • Acne specific inclusion criteria:

    o 10-100 noninflammatory, 20-50 inflammatory lesions (nose excluded)

  • Rosacea specific inclusion criteria:

    • History of frequent flushing
    • Skin erythema - Positive (not negative) chromometer minimum reading difference when subtracting nonaffected reading from affected reading.

Goal would be greater than 1 unit difference between red areas. For example, the red area (average 17.7 Chroma Meter a) and nonaffected areas (average 14.1 Chroma Meter a), yields in an optimum scenario greater than 3 point difference in this example (in subjects with average Chromometer L value averaging 56.6-59.6). Example from (Helfrich et al., 2015).

o Presence of inflammatory papules

Exclusion Criteria:

  • Having received any investigational drug within 30 days prior to study entry
  • An allergy history to any study materials including any beta-blockers.
  • Pregnant, lactating, or trying to become pregnant
  • Severe depression
  • Hypotension or history
  • Bradycardia or history
  • History of Cardiac Heart Failure
  • History of Myocardial infarction
  • History of heart arrhythmia
  • Asthma or Bronchospasm or history
  • Rosacea specific exclusion criteria:

Recent topicals within 3 weeks Oral rosacea medications such as antibiotics within 3 weeks • Acne specific exclusion criteria: nodular acne man with beard which interferes with clinical evaluation history of Accutane Oral contraceptive pills changes last 3 months Topical retinoid within 4 weeks Cosmetic procedures (like facial or peels) for 4 weeks Photodynamic therapy , laser therapy or microdermabrasion for 4 weeks Other topicals or oral acne medications such as antibiotics within 3 weeks

o Biopsy volunteer specific exclusion criteria: History of keloids History of hypertrophic scars Allergy to lidocaine or epinephrine

Sites / Locations

  • Johns Hopkins Dermatology Department

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Timolol to split face for 8 weeks

Arm Description

All 24 subjects will receive study drug and everyone will be randomized to which side of the face is treated with study drug first (right half-face versus left half-face). After 8 weeks of split-face treatment every night before bed, the subjects will be instructed to start treating both sides for another 8 weeks. Up to 30 subjects may be enrolled to ensure a target sample size of 24 (12 acne cases, 12 rosacea cases). This is an exploratory study. No part of this protocol will be considered routine care.

Outcomes

Primary Outcome Measures

Safety and tolerability of timolol for acne and rosacea as assessed by subject report
To determine the safety and tolerability of Timolol in the treatment of acne and rosacea
Safety and tolerability of timolol for acne and rosacea as assessed by physician assessment
To determine the safety and tolerability of Timolol in the treatment of acne and rosacea

Secondary Outcome Measures

Decrease of rosacea activity as assessed through visual assessments (photographs, chronometer, patient report and physician examination)
In rosacea, to measure decreases of disease activity-- redness.
Decrease of acne activity: papules
In acne, to measure decreases of disease activity: papules
Test if the DNA methylation patterns are corrected following clinical improvement as assessed by microarray
In both conditions, test if the DNA methylation patterns specific to each is corrected following clinical improvement after timolol treatment.

Full Information

First Posted
May 9, 2016
Last Updated
November 4, 2021
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT02774590
Brief Title
Timolol for the Treatment of Acne and Rosacea
Official Title
Timolol for the Treatment of Acne and Rosacea
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
March 2021 (Actual)
Study Completion Date
March 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This research is being done to determine the safety and tolerability of timolol in the treatment of acne and rosacea. The investigators will also look for specific biomolecular changes in acne or rosacea skin when it is exposed to timolol. Timolol is approved by the Food and Drug Administration (FDA) for the treatment of glaucoma. In dermatology, it has been used as a treatment to decrease the size of vascular (blood vessel) malformations in infant skin. Timolol is not approved for use in acne or rosacea and its use in this study is investigational. Many people with rosacea have telangiectasias which are small, red dilated blood vessels on the skin. They also suffer from flushing and acne-like lesions. Better treatments than those currently available are desired. Acne vulgaris, or acne, is another chronic inflammatory and very common skin disease that affects about 8 out of 10 young adults and adolescents. Signs of acne include papules and blackheads that are often called primary lesions because they represent an active form of the disease. There are also secondary lesions that can form later; they are known as acne scars
Detailed Description
Rosacea affects roughly 16 million Americans who desire better treatments than those currently available. Acne vulgaris, another chronic inflammatory skin disorder, mainly affects teenagers but also affects 20-40% of adults. Investigating potential new treatments will not only satisfy a clinical need, but also offers the opportunity to learn about the pathogenesis of the disease and skin biology. The purpose of this study is to investigate the possible role of timolol as a therapy for the erythema and papules associated with acne and rosacea. It has been shown that timolol is beneficial and safe to treat infantile hemangiomas. The investigators hypothesize that it may also be safe and effective in the treatment of acne and rosacea. In a single experiment where the test case was the PI (a practicing physician), the investigators treated his rosacea with timolol for this off-label indication and have noticed an improvement in flushing and an unexpected improvement in acneiform eruptions associated with the rosacea. After 30 days, less flushing and acneiform lesions were noted on the treated right side compared to the left side . Similarly, at 60 days after treatment, as visualized by infrared imaging, significantly less inflammation and flushing was noted on the treated right side even outside of episodes of flushing. The improvement was durable, such that after a 60 day washout, improvements were still noted. In summary, during testing of the PI as a case subject, timolol appeared effective, safe, and with some disease-remissive effects. Our aim is to conduct a 16 week split-face pilot study with up to 30 patients who have a diagnosis of either inflammatory acne or rosacea to assess whether timolol maleate effectively reduces erythema, flushing, telangiectasias, and/or papules. The investigators also propose to biopsy a subset of our study patients to examine the biological activity in the skin before and after treatment. The investigators are particularly interested in studying epigenetic DNA methylation abnormalities in these conditions at baseline to compare to normal subjects and as a result of therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acne Vulgaris, Rosacea
Keywords
Acne vulgaris, Rosacea

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Timolol to split face for 8 weeks
Arm Type
Experimental
Arm Description
All 24 subjects will receive study drug and everyone will be randomized to which side of the face is treated with study drug first (right half-face versus left half-face). After 8 weeks of split-face treatment every night before bed, the subjects will be instructed to start treating both sides for another 8 weeks. Up to 30 subjects may be enrolled to ensure a target sample size of 24 (12 acne cases, 12 rosacea cases). This is an exploratory study. No part of this protocol will be considered routine care.
Intervention Type
Drug
Intervention Name(s)
Timolol
Intervention Description
Apply timolol on half of the participant's face for 8 weeks. Then treat both sides of face for 8 weeks.
Primary Outcome Measure Information:
Title
Safety and tolerability of timolol for acne and rosacea as assessed by subject report
Description
To determine the safety and tolerability of Timolol in the treatment of acne and rosacea
Time Frame
8 weeks
Title
Safety and tolerability of timolol for acne and rosacea as assessed by physician assessment
Description
To determine the safety and tolerability of Timolol in the treatment of acne and rosacea
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Decrease of rosacea activity as assessed through visual assessments (photographs, chronometer, patient report and physician examination)
Description
In rosacea, to measure decreases of disease activity-- redness.
Time Frame
8 weeks
Title
Decrease of acne activity: papules
Description
In acne, to measure decreases of disease activity: papules
Time Frame
8 weeks
Title
Test if the DNA methylation patterns are corrected following clinical improvement as assessed by microarray
Description
In both conditions, test if the DNA methylation patterns specific to each is corrected following clinical improvement after timolol treatment.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In the opinion of the investigator, must be medically able to undergo the administration of study material Be able to comprehend the informed consent document and provide consent for participation Females of childbearing potential must: Not be pregnant by subjective report agree to not become pregnant or breastfeed for the period of the study through 1 month after completion of the study be willing to use a reliable form of contraception during the study Be willing and able to comply with the scheduled visits and other study procedures for the duration of the study. Be willing not to take any other medicine for acne or rosacea during the study Acne specific inclusion criteria: o 10-100 noninflammatory, 20-50 inflammatory lesions (nose excluded) Rosacea specific inclusion criteria: History of frequent flushing Skin erythema - Positive (not negative) chromometer minimum reading difference when subtracting nonaffected reading from affected reading. Goal would be greater than 1 unit difference between red areas. For example, the red area (average 17.7 Chroma Meter a) and nonaffected areas (average 14.1 Chroma Meter a), yields in an optimum scenario greater than 3 point difference in this example (in subjects with average Chromometer L value averaging 56.6-59.6). Example from (Helfrich et al., 2015). o Presence of inflammatory papules Exclusion Criteria: Having received any investigational drug within 30 days prior to study entry An allergy history to any study materials including any beta-blockers. Pregnant, lactating, or trying to become pregnant Severe depression Hypotension or history Bradycardia or history History of Cardiac Heart Failure History of Myocardial infarction History of heart arrhythmia Asthma or Bronchospasm or history Rosacea specific exclusion criteria: Recent topicals within 3 weeks Oral rosacea medications such as antibiotics within 3 weeks • Acne specific exclusion criteria: nodular acne man with beard which interferes with clinical evaluation history of Accutane Oral contraceptive pills changes last 3 months Topical retinoid within 4 weeks Cosmetic procedures (like facial or peels) for 4 weeks Photodynamic therapy , laser therapy or microdermabrasion for 4 weeks Other topicals or oral acne medications such as antibiotics within 3 weeks o Biopsy volunteer specific exclusion criteria: History of keloids History of hypertrophic scars Allergy to lidocaine or epinephrine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luis A Garza, MD, PhD
Organizational Affiliation
Johns Hopkins Dermatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Dermatology Department
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21209
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Following publication the investigators will honor all requests for original data
Citations:
PubMed Identifier
33548303
Citation
Tsai J, Chien AL, Kim N, Rachidi S, Connolly BM, Lim H, Alessi Cesar SS, Kang S, Garza LA. Topical timolol 0.5% gel-forming solution for erythema in rosacea: A quantitative, split-face, randomized, and rater-masked pilot clinical trial. J Am Acad Dermatol. 2021 Oct;85(4):1044-1046. doi: 10.1016/j.jaad.2021.01.098. Epub 2021 Feb 3. No abstract available.
Results Reference
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Timolol for the Treatment of Acne and Rosacea

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