Open Angle GlaucomaPhase 4NCT02053298
Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients
A Phase 4 study testing Timolol & Dorzolamide in people with Open Angle Glaucoma, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Glaucoma is an optic neuropathy in which the main risk factor is intraocular pressure (IOP). The search for other variables involved in glaucoma pathogenesis and progression has identified both systemic and ocular signs of vascular dysfunction in glaucoma patients, such as migraine, peripheral vasospasm, systemic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Open Angle Glaucoma
- What is being tested?
- Timolol & Dorzolamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBelgium
- Study dates
- Jan 2014to Dec 2015
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- individuals over 18 years old
- willing to sign an informed consent and able to comply with the requirements of the study
- having no other ocular diseases besides glaucoma associated with hemodynamic disturbances
- being either under no topical therapy (naïve patients) or under IOP-lowering monotherapy
Who cannot join
- history of ocular trauma
- intraocular surgery (except for cataract surgery)
- eye disease associated with hemodynamic disturbances (except glaucoma)
- systemic diseases with ocular involvement like diabetes
- contra-indications to the use of topical beta-blockers or carbonic anhydrase inhibitors
Trial locations and contacts
1 site in 1 country.
Belgium1 site
University Hospitals Leuven
Leuven, Flemish Brabant, 3000 Leuven
About this study
Glaucoma is an optic neuropathy in which the main risk factor is intraocular pressure (IOP). The search for other variables involved in glaucoma pathogenesis and progression has identified both systemic and ocular signs of vascular dysfunction in glaucoma patients, such as migraine, peripheral vasospasm, systemic hypotension and cerebral microvascular ischemia. Ocular blood flow studies using Color Doppler Imaging (CDI) technology has demonstrated blood velocities and increased vascular resistance (RI) to exist in such patients when compared to healthy controls. However, a CDI examination provides far more additional information, such as arterial pulsatility (PI) and mean blood velocities (MFV). While these have been used for decades now to study cerebral arteries vasoreactivity, little is known about how these variables are changed in glaucoma patients. We have recently demonstrated that these variables can be used to identify a change in the normal vascular activity when there is increased resistance. In glaucoma patients, a cutpoint in RI of the retrobulbar arteries could be determined beyond which PI increased significantly. This sharp increase in the PI has been used as an indirect signal that the vessel's ability to buffer a decreased perfusion pressure has been surpassed. The normal response to a decreased perfusion in a vascular territory with autoregulation is an increase in dilation in the downstream microcirculation, increasing cross section area in an attempt to keep a steady MFV. As PI is calculated using the vessel's MFV [PI = (PSV-EDV)/MFV], it is highly sensitive to changes in this variable. As such, the cutpoints we have identified in glaucoma patients are therefore an indirect assessment of the vessel's autoregulation limit.
While our data could provide the rational as to why these RI values are associated with progression, the clinical question arises as to whether these cutpoints can be modulated by topical glaucoma therapy. As some medications such as carbonic anhydrase inhibitors have been found to have a positive effect in disease progression in what appears to be a non-IOP related effect, we considered the hypothesis that these drugs could have a positive impact on the ocular's microcirculation vasoactive response, potentially enabling to keep a steady MFV into higher values of vascular resistance.
Read the detailed description
Patients will be recruited from the glaucoma clinic at the department of Ophthalmology in the Leuven University Hospital.
General study setup:
Two cohorts of subjects will be included in the study: primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. At the screening visit, eligible patients will have their topical therapy replaced by timolol 0.5% bid. At week 4, dorzolamide 2% will be added to the existing treatment in a fixed combination therapy (timolol 0.5%+dorzolamide 2% bid). A final visit at week 8.
At the screening visit (day 0), the patients will undergo a complete ophthalmic investigation with visual acuity, slit lamp biomicroscopy, tonometry, 90 D fundoscopy, automated perimetry, Heidelberg retinal tomography and color Doppler imaging. Blood pressure will also be measured. Topical monotherapy will be replaced by timolol 0.5% bid.
At visit 1 and 2 (timolol - week 4, timolol+dorzolamide week 8, respectively), the patients will undergo ophthalmic investigation with visual acuity, slit lamp biomicroscopy, tonometry, 90 D fundoscopy, blood pressure measurement and color Doppler imaging.
Only one eye will be selected for the study (eye with worst glaucomatous damage). Mann-Whitney test will be used in pairwise comparisons. Restricted cubic sp-lines will be used to verify if there is any evidence for nonlinearity in the relation between the RI and PI. Piecewise linear regression models will be used to determine the optimal cutpoint (i.e. the cutpoint yielding the highest likelihood) in all three visits (baseline, timolol and timolol/dorzolamide). Sensitivity analyses will be performed to verify if the result is not due to an (influential) subject with a high RI value. All data will be expressed in mean ± standard deviation. A two sided p-value <0.05 is considered significant.
Sample size calculations were made to address the primary outcome (i.e., a change in the RI cutpoints between baseline and last study visit) in the overall glaucoma population (POAG+NTG patients). Based on our previous results10, setting an α error to 5%, power at 80% and the allowable difference at 10% would require the recruitment of 40 patients. Further post hoc analysis will be made to identify differences between the two study cohorts.
- Conditions
- Open Angle Glaucoma
- Being tested
- Timolol & Dorzolamide
- Keywords
- Glaucoma
- Medical subject headings
- Glaucoma, Open-Angle, Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timolol & DorzolamideDrug
Also called Cosopt UD
Topical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month
| Study group | Role | What they receive |
|---|---|---|
| Timolol & Dorzolamide | Experimental | Topical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month Receives: Drug: Timolol & Dorzolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retrobulbar vascular resistance cutpoint change
The retrobulbar vascular resistance point at which the pulsatility changes will be measured before (baseline), under topical timolol 0.5% and under topical timolol 0.5+dorzolamide 2%
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2014 (estimated)
- Study startJan 2014
- Primary completionDec 2015
- Study completionDec 2015
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 Open Angle GlaucomaStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ingeborg Stalmans, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02053298
- Sponsor's protocol ID
- S - 54854
- Status last verified
- Jul 2024
- First submitted
- 31 Jan 2014
- Last updated
- 16 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Abegao Pinto L, Vandewalle E, Stalmans I. Disturbed correlation between arterial resistance and pulsatility in glaucoma patients. Acta Ophthalmol. 2012 May;90(3):e214-20. doi: 10.1111/j.1755-3768.2011.02335.x. Epub 2012 Jan 23.
PubMed 22268445
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients
- ClinicalTrials.gov ID
- NCT02053298
- Acronym / sponsor ID
- S - 54854
- Conditions
- Open Angle Glaucoma
- Keywords
- Glaucoma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 3 Feb 2014 (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.
Glaucoma is an optic neuropathy in which the main risk factor is intraocular pressure (IOP). The search for other variables involved in glaucoma pathogenesis and progression has identified both systemic and ocular signs of vascular dysfunction in glaucoma patients, such as migraine, peripheral vasospasm, systemic hypotension and cerebral microvascular ischemia. Ocular blood flow studies using Color Doppler Imaging (CDI) technology has demonstrated blood velocities and increased vascular resistance (RI) to exist in such patients when compared to healthy controls. However, a CDI examination provides far more additional information, such as arterial pulsatility (PI) and mean blood velocities (MFV). While these have been used for decades now to study cerebral arteries vasoreactivity, little is known about how these variables are changed in glaucoma patients. We have recently demonstrated that these variables can be used to identify a change in the normal vascular activity when there is increased resistance. In glaucoma patients, a cutpoint in RI of the retrobulbar arteries could be determined beyond which PI increased significantly. This sharp increase in the PI has been used as an indirect signal that the vessel's ability to buffer a decreased perfusion pressure has been surpassed. The normal response to a decreased perfusion in a vascular territory with autoregulation is an increase in dilation in the downstream microcirculation, increasing cross section area in an attempt to keep a steady MFV. As PI is calculated using the vessel's MFV [PI = (PSV-EDV)/MFV], it is highly sensitive to changes in this variable. As such, the cutpoints we have identified in glaucoma patients are therefore an indirect assessment of the vessel's autoregulation limit.
While our data could provide the rational as to why these RI values are associated with progression, the clinical question arises as to whether these cutpoints can be modulated by topical glaucoma therapy. As some medications such as carbonic anhydrase inhibitors have been found to have a positive effect in disease progression in what appears to be a non-IOP related effect, we considered the hypothesis that these drugs could have a positive impact on the ocular's microcirculation vasoactive response, potentially enabling to keep a steady MFV into higher values of vascular resistance.
Detailed description
Patients will be recruited from the glaucoma clinic at the department of Ophthalmology in the Leuven University Hospital.
General study setup:
Two cohorts of subjects will be included in the study: primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) patients. At the screening visit, eligible patients will have their topical therapy replaced by timolol 0.5% bid. At week 4, dorzolamide 2% will be added to the existing treatment in a fixed combination therapy (timolol 0.5%+dorzolamide 2% bid). A final visit at week 8.
At the screening visit (day 0), the patients will undergo a complete ophthalmic investigation with visual acuity, slit lamp biomicroscopy, tonometry, 90 D fundoscopy, automated perimetry, Heidelberg retinal tomography and color Doppler imaging. Blood pressure will also be measured. Topical monotherapy will be replaced by timolol 0.5% bid.
At visit 1 and 2 (timolol - week 4, timolol+dorzolamide week 8, respectively), the patients will undergo ophthalmic investigation with visual acuity, slit lamp biomicroscopy, tonometry, 90 D fundoscopy, blood pressure measurement and color Doppler imaging.
Only one eye will be selected for the study (eye with worst glaucomatous damage). Mann-Whitney test will be used in pairwise comparisons. Restricted cubic sp-lines will be used to verify if there is any evidence for nonlinearity in the relation between the RI and PI. Piecewise linear regression models will be used to determine the optimal cutpoint (i.e. the cutpoint yielding the highest likelihood) in all three visits (baseline, timolol and timolol/dorzolamide). Sensitivity analyses will be performed to verify if the result is not due to an (influential) subject with a high RI value. All data will be expressed in mean ± standard deviation. A two sided p-value <0.05 is considered significant.
Sample size calculations were made to address the primary outcome (i.e., a change in the RI cutpoints between baseline and last study visit) in the overall glaucoma population (POAG+NTG patients). Based on our previous results10, setting an α error to 5%, power at 80% and the allowable difference at 10% would require the recruitment of 40 patients. Further post hoc analysis will be made to identify differences between the two study cohorts.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Timolol & Dorzolamide | Experimental | Drug: Timolol & DorzolamideTopical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- individuals over 18 years old
- willing to sign an informed consent and able to comply with the requirements of the study
- having no other ocular diseases besides glaucoma associated with hemodynamic disturbances
- being either under no topical therapy (naïve patients) or under IOP-lowering monotherapy
Key exclusion criteria (5 listed)
- history of ocular trauma
- intraocular surgery (except for cataract surgery)
- eye disease associated with hemodynamic disturbances (except glaucoma)
- systemic diseases with ocular involvement like diabetes
- contra-indications to the use of topical beta-blockers or carbonic anhydrase inhibitors
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 & DorzolamideAlso: Cosopt UDTopical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month | Drug | Timolol & Dorzolamide |
Primary outcome
Retrobulbar vascular resistance cutpoint change
Time frame: 2 months
The retrobulbar vascular resistance point at which the pulsatility changes will be measured before (baseline), under topical timolol 0.5% and under topical timolol 0.5+dorzolamide 2%
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 16 Jul 2024.
- Background: PubMed 22268445Abegao Pinto L, Vandewalle E, Stalmans I. Disturbed correlation between arterial resistance and pulsatility in glaucoma patients. Acta Ophthalmol. 2012 May;90(3):e214-20. doi: 10.1111/j.1755-3768.2011.02335.x. Epub 2012 Jan 23.
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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.
Ingeborg Stalmans, MD, PhD principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Timolol & Dorzolamide in people with Open Angle Glaucoma, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 4 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 16 Jul 2024. 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 Belgium. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Retrobulbar vascular resistance cutpoint change (time frame: 2 months). 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 NCT02053298, 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 16 Jul 2024.