Glaucoma, Open-AngleNCT04903366
Absorption and Safety of Topical Timolol to Treat Chronic Wounds
An observational study of Glaucoma, Open-Angle and Chronic Wounds, run by VA Northern California Health Care System at 1 site in United States.
Trial summary
Topical timolol has been used primarily as eye drops to treat glaucoma for many years. Recent clinical experience has broadened its off-label use for a number of skin conditions, including slow-healing wounds. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glaucoma, Open-Angle, Chronic Wounds
- What is being tested?
- Timolol Maleate
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2017to 14 Jan 2020
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Veterans treated at VA Northern California Health Care System from the Dermatology Wound Clinic and the Eye Clinic.
Who may be able to join
- Over 18 years of age
- Using physician-prescribed timolol as directed
- The ability to read, understand, and sign informed consent for blood draw and release of medical information forms
- For wound group: documented chronic wound (greater than 30 days, with minimal improvement), with any type of wound.
- For glaucoma group: diagnosed with ocular hypertension or open-angle glaucoma.
Who cannot join
- Patient is not currently prescribed timolol or currently taking oral metoprolol
- History of any type of heart block
- History of bradycardia (heart-rate less than 60 beats per minute (bpm))
- History of documented hypotension
- History of asthma or chronic obstructive pulmonary disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Northern California Health Care System
Mather, California, 95655
About this study
Official title: Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds
Topical timolol has been used primarily as eye drops to treat glaucoma for many years. Recent clinical experience has broadened its off-label use for a number of skin conditions, including slow-healing wounds. While there have been extensive safety studies performed on timolol administration to treat the eye, to date, no studies have documented absorption of timolol after applied on chronic wounds. Thus, the purpose of this study is to determine the blood levels of timolol in patients after topical administration to a chronic wound, and compare these levels with those of patients after administration of the same drug formulation on the eye for the indication of glaucoma.
Read the detailed description
Chronic wounds, such as diabetic foot ulcers, venous leg ulcers and pressure ulcers are serious problems in our health system, with limited therapeutic options available to improve healing. Our laboratory and animal work has suggested that timolol, a safe medication, currently used as an eye drop for treatment of glaucoma, can heal these ulcers.
Timolol, is a nonselective, beta1/beta2 adrenergic receptor antagonist, widely used for the management of ocular hypertension or open-angle glaucoma. Most recently, there have been many case reports published that suggest that timolol can be used topically to aid in the healing of chronic, recalcitrant ulcers and wounds; however, concern over the medication's systemic effects needs to be further explored and elucidated. The systemic absorption of timolol eye drops and the medications systemic side effects have been well established; however, this has not before been examined in patients receiving topical timolol for chronic wounds. Now that this beta blocker has promising evidence for a role in the topical management of chronic wounds, the safety of this drug in topical use is of interest.
The importance of this study is in the exploration of the safety of timolol in the topical treatment of chronic wounds. If the systemic absorption from topical application to chronic wounds is found to be equivalent or less than that from ophthalmic drops, then a strong argument can be made regarding the relative safety of Timolol.
To investigate the safety profile of topical timolol application, blood levels will be measured to determine the systemic absorption of timolol. To do this, we proposed an observational cross-sectional comparative study with two groups of patients: one group receiving topical timolol for chronic wounds and the other receiving ophthalmic timolol for the management of glaucoma. Serum levels of timolol will be quantified using high performance liquid chromatography (HPLC), and the levels between the two groups will be compared.
- Conditions
- Glaucoma, Open-Angle, Chronic Wounds
- Being tested
- Timolol Maleate
- Keywords
- Timolol, Catecholamine, Absorption
- Medical subject headings
- Glaucoma, Open-Angle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol MaleateDrug
timolol maleate 0.5% gel-forming solution
| Study group | Role | What they receive |
|---|---|---|
| Chronic wound | Any chronic wound, for greater than 30 days with minimal improvement Receives: Drug: Timolol Maleate | |
| Glaucoma | Any diagnosis of glaucoma and active prescription of timolol drops Receives: Drug: Timolol Maleate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean plasma concentration of timolol in each group
For both groups, after administration of timolol drops as prescribed, one 6 mL blood was drawn. After centrifugation, the plasma from both groups was frozen at -80°C until assay.
Measured: Blood was drawn 1 hour after drug administration
Secondary outcomes (2)
Systemic levels of timolol dose per body weight
Measurement of timolol dose per kilogram body weight plotted against the systemic plasma timolol level
Measured: Blood was drawn 1 hour after drug administration
Systemic levels of timolol by dose and wound type
Measurement of mean plasma levels of timolol in the different wound categories (e.g., venous, diabetic, pressure ulcer
Measured: Blood was drawn 1 hour after drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2021
- Study start21 Nov 2017
- Primary completion9 Mar 2018
- Study completion14 Jan 2020
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 Glaucoma, Open-AngleStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Northern California Health Care System
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Roslyn Rivkah Isseroff, M.D., VA Northern California Health Care System
- Investigators
- Rivkah R Isseroff, MD, Principal investigator, VA Northern California Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04903366
- Sponsor's protocol ID
- 17-10-00798
- Status last verified
- May 2021
- First submitted
- 21 May 2021
- Last updated
- 27 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gallegos AC, Davis MJ, Tchanque-Fossuo CN, West K, Eisentrout-Melton A, Peavy TR, Dixon RW, Patel RP, Dahle SE, Isseroff RR. Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds. Adv Wound Care (New Rochelle). 2019 Nov 1;8(11):538-545. doi: 10.1089/wound.2019.0970. Epub 2019 Oct 16.
PubMed 31637100
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds
- ClinicalTrials.gov ID
- NCT04903366
- Acronym / sponsor ID
- 17-10-00798
- Conditions
- Glaucoma, Open-Angle, Chronic Wounds
- Keywords
- Timolol, Catecholamine, Absorption
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- VA Northern California Health Care SystemUS federal agency
- Study start
- 21 Nov 2017 (actual)
- Primary completion
- 9 Mar 2018 (actual)
- Study completion
- 14 Jan 2020 (actual)
- First posted
- 26 May 2021 (actual)
- 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.
Topical timolol has been used primarily as eye drops to treat glaucoma for many years. Recent clinical experience has broadened its off-label use for a number of skin conditions, including slow-healing wounds. While there have been extensive safety studies performed on timolol administration to treat the eye, to date, no studies have documented absorption of timolol after applied on chronic wounds. Thus, the purpose of this study is to determine the blood levels of timolol in patients after topical administration to a chronic wound, and compare these levels with those of patients after administration of the same drug formulation on the eye for the indication of glaucoma.
Detailed description
Chronic wounds, such as diabetic foot ulcers, venous leg ulcers and pressure ulcers are serious problems in our health system, with limited therapeutic options available to improve healing. Our laboratory and animal work has suggested that timolol, a safe medication, currently used as an eye drop for treatment of glaucoma, can heal these ulcers.
Timolol, is a nonselective, beta1/beta2 adrenergic receptor antagonist, widely used for the management of ocular hypertension or open-angle glaucoma. Most recently, there have been many case reports published that suggest that timolol can be used topically to aid in the healing of chronic, recalcitrant ulcers and wounds; however, concern over the medication's systemic effects needs to be further explored and elucidated. The systemic absorption of timolol eye drops and the medications systemic side effects have been well established; however, this has not before been examined in patients receiving topical timolol for chronic wounds. Now that this beta blocker has promising evidence for a role in the topical management of chronic wounds, the safety of this drug in topical use is of interest.
The importance of this study is in the exploration of the safety of timolol in the topical treatment of chronic wounds. If the systemic absorption from topical application to chronic wounds is found to be equivalent or less than that from ophthalmic drops, then a strong argument can be made regarding the relative safety of Timolol.
To investigate the safety profile of topical timolol application, blood levels will be measured to determine the systemic absorption of timolol. To do this, we proposed an observational cross-sectional comparative study with two groups of patients: one group receiving topical timolol for chronic wounds and the other receiving ophthalmic timolol for the management of glaucoma. Serum levels of timolol will be quantified using high performance liquid chromatography (HPLC), and the levels between the two groups will be compared.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic wound | – | Drug: Timolol MaleateAny chronic wound, for greater than 30 days with minimal improvement |
| Glaucoma | – | Drug: Timolol MaleateAny diagnosis of glaucoma and active prescription of timolol drops |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Veterans treated at VA Northern California Health Care System from the Dermatology Wound Clinic and the Eye Clinic.
Key inclusion criteria (5 listed)
- Over 18 years of age
- Using physician-prescribed timolol as directed
- The ability to read, understand, and sign informed consent for blood draw and release of medical information forms
- For wound group: documented chronic wound (greater than 30 days, with minimal improvement), with any type of wound.
- For glaucoma group: diagnosed with ocular hypertension or open-angle glaucoma.
Key exclusion criteria (5 listed)
- Patient is not currently prescribed timolol or currently taking oral metoprolol
- History of any type of heart block
- History of bradycardia (heart-rate less than 60 beats per minute (bpm))
- History of documented hypotension
- History of asthma or chronic obstructive pulmonary disease.
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 |
|---|---|---|
| Timolol Maleatetimolol maleate 0.5% gel-forming solution | Drug | Chronic wound, Glaucoma |
Primary outcome
Mean plasma concentration of timolol in each group
Time frame: Blood was drawn 1 hour after drug administration
For both groups, after administration of timolol drops as prescribed, one 6 mL blood was drawn. After centrifugation, the plasma from both groups was frozen at -80°C until assay.
2 secondary outcomes
Systemic levels of timolol dose per body weight
Time frame: Blood was drawn 1 hour after drug administration
Systemic levels of timolol by dose and wound type
Time frame: Blood was drawn 1 hour after drug administration
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 27 May 2021.
- Background: PubMed 31637100Gallegos AC, Davis MJ, Tchanque-Fossuo CN, West K, Eisentrout-Melton A, Peavy TR, Dixon RW, Patel RP, Dahle SE, Isseroff RR. Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds. Adv Wound Care (New Rochelle). 2019 Nov 1;8(11):538-545. doi: 10.1089/wound.2019.0970. Epub 2019 Oct 16.
- Individual participant dataSharing planned: No
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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.
Rivkah R Isseroff, MD principal investigator
VA Northern California Health Care System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glaucoma, Open-Angle and Chronic Wounds, run by VA Northern California Health Care System 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 5 inclusion and 5 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 27 May 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.
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?
Mean plasma concentration of timolol in each group (time frame: Blood was drawn 1 hour after drug administration). 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 NCT04903366, 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 27 May 2021.