Acne VulgarisPhase 1NCT02774590
Timolol for the Treatment of Acne and Rosacea
A Phase 1 study testing Timolol in people with Acne Vulgaris and Rosacea, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acne Vulgaris, Rosacea
- What is being tested?
- Timolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Dermatology Department
Baltimore, Maryland, 21209
About this study
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.
Read more
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
Read the 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.
- Conditions
- Acne Vulgaris, Rosacea
- Being tested
- Timolol
- Keywords
- Acne vulgaris, Rosacea
- Medical subject headings
- Acne Vulgaris, Rosacea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TimololDrug
Apply timolol on half of the participant's face for 8 weeks. Then treat both sides of face for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Timolol to split face for 8 weeks | Experimental | 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. Receives: Drug: Timolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 8 weeks
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
Measured: 8 weeks
Secondary outcomes (3)
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.
Measured: 8 weeks
Decrease of acne activity: papules
In acne, to measure decreases of disease activity: papules
Measured: 8 weeks
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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2016 (estimated)
- Study startMar 2016
- Primary completionMar 2021
- Study completionMar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acne VulgarisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luis A Garza, MD, PhD, Principal investigator, Johns Hopkins Dermatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02774590
- Sponsor's protocol ID
- IRB00074049
- Status last verified
- Jan 2021
- First submitted
- 9 May 2016
- Last updated
- 11 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Following publication the investigators will honor all requests for original data
Publications
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.
PubMed 33548303
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Timolol for the Treatment of Acne and Rosacea
- ClinicalTrials.gov ID
- NCT02774590
- Acronym / sponsor ID
- IRB00074049
- Conditions
- Acne Vulgaris, Rosacea
- Keywords
- Acne vulgaris, Rosacea
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Mar 2021 (actual)
- Study completion
- Mar 2021 (actual)
- First posted
- 17 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Timolol to split face for 8 weeks | Experimental | Drug: TimololAll 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TimololApply timolol on half of the participant's face for 8 weeks. Then treat both sides of face for 8 weeks. | Drug | Timolol to split face for 8 weeks |
Primary outcome
Safety and tolerability of timolol for acne and rosacea as assessed by subject report
Time frame: 8 weeks
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
Time frame: 8 weeks
To determine the safety and tolerability of Timolol in the treatment of acne and rosacea
3 secondary outcomes
Decrease of rosacea activity as assessed through visual assessments (photographs, chronometer, patient report and physician examination)
Time frame: 8 weeks
Decrease of acne activity: papules
Time frame: 8 weeks
Test if the DNA methylation patterns are corrected following clinical improvement as assessed by microarray
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Results publication: PubMed 33548303Tsai 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.
- Individual participant dataSharing planned: Yes. Following publication the investigators will honor all requests for original data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis A Garza, MD, PhD principal investigator
Johns Hopkins Dermatology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Timolol in people with Acne Vulgaris and Rosacea, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of timolol for acne and rosacea as assessed by subject report (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02774590, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.