Timolol for the Treatment of Acne and Rosacea

NCT ID: NCT02774590

Last Updated: 2021-11-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

8 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2021-03-31

Brief Summary

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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

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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.

Conditions

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Acne Vulgaris Rosacea

Keywords

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Acne vulgaris Rosacea

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Timolol to split face for 8 weeks

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.

Group Type EXPERIMENTAL

Timolol

Intervention Type DRUG

Apply timolol on half of the participant's face for 8 weeks. Then treat both sides of face for 8 weeks.

Interventions

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Timolol

Apply timolol on half of the participant's face for 8 weeks. Then treat both sides of face for 8 weeks.

Intervention Type DRUG

Eligibility Criteria

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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

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

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Luis A Garza, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Dermatology

Locations

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Johns Hopkins Dermatology Department

Baltimore, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 33548303 (View on PubMed)

Other Identifiers

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IRB00074049

Identifier Type: -

Identifier Source: org_study_id