Eye DiseasePhase 4DIOXXACTNCT00957190
The DIOXXACT Trial(Diurnal IOP and OBF Xalatan vs Xalatan And Cosopt Trial)
A Phase 4 study testing Dorzolamide 20 mg and Timolol 5 mg in people with Eye Disease, run by Maisonneuve-Rosemont Hospital at 1 site in Canada.
Trial summary
Diurnal and intervisit fluctuations in IOP are strongly associated with progression of open angle glaucoma and therefore need to be minimized. Control of diurnal fluctuations of IOP with different ocular hypotensive medications has been studied in some detail. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Eye Disease
- What is being tested?
- Dorzolamide 20 mg and Timolol 5 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- 4 May 2009to Feb 2012
- 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjets with open angle glaucoma or ocular hypertension currently on latanoprost immunotherapy.
- Subjets must have clear media, corrected visual acuity of 6/12 or better,and be able to sit for imaging.
Who cannot join
- Subjets with contraindications or known allergies to any of the components of Cosopt.
- Subjets who had undergoing laser or any ocular surgery.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Change in Optic Nerve Head Blood Flow,Optic Nerve Topography and Diurnal Fluctuation of Intraocular Pressure and Pulsatile Ocular Blood Flow in Glaucoma:Cosopt and Xalatan vs Xalatan Alone
Diurnal and intervisit fluctuations in IOP are strongly associated with progression of open angle glaucoma and therefore need to be minimized. Control of diurnal fluctuations of IOP with different ocular hypotensive medications has been studied in some detail. But how do IOP changes contribute to progressive glaucomatous optic nerve damage? It is reasonable to assume that there are two principal effects of IOP changes. First, IOP fluctuations result in changes in the stresses and strains on the ONH which in turn result in morphological changes to the ONH. These morphological changes could in turn result in stretching and damage to axons of the ONH. Secondly, IOP fluctuations results in changes to the forces acting on the ONH vasculature, leading to changes in ONH vascular perfusion. These changes to perfusion could in turn result in relative ischemia of the ONH and consequent ONH damage.
The investigators propose to monitor diurnal fluctuations in IOP and choroidal blood flow (Pulsatile Ocular Blood Flow,POBF), and intervisit ONH topographical and blood flow changes-ie to monitor the direct ONH consequences of IOP . Open angle glaucoma patients are commonly prescribed topical latanoprost as first line therapy. The EXACCT study, for which I was the principal investigator and which is now submitted for publication, demonstrated that COSOPT was an efficacious choice as second line therapy for patients not controlled on latanoprost monotherapy. The investigators will therefore recruit 20 OAG patients on latanoprost monotherapy, perform diurnal curves of IOP, as well as a.m. ONH morphology and ONH blood flow. Cosopt will then be added and at the next visit the same measurements will be repeated.
The investigators expect that when Cosopt is added the investigators will demonstrate improved IOP, morphology and blood flow compared to the latanoprost baseline. Furthermore the investigators expect the the diurnal fluctuation of IOP and choroidal blood flow will be stabilized on Cosopt therapy. The implications are that adding Cosopt to latanoprost can stabilize not only the IOP but also the damaging consequences of IOP to the optic nerve head.
Read the detailed description
Twenty patients with open angle glaucoma or ocular hypertension currently on latanoprost immunotherapy will be recruited.
A complete routine ophthalmic examination including biomicroscopy, gonioscopy and fundus ophthalmoscopy will be performed. The eye with better visual acuity is selected for fundus flowmetry.
All patients will undergo a complete diurnal workup including IOP, as well as 10am Confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography-3) of ONH topography. Optic nerve head, nasal and temporal peripapillary retinal blood flow are measured with scanning laser Doppler flowmetry (SLDF; Heidelberg Retinal Flowmeter/Tomograph, SLDF analysis software v3.3, Heidelberg Engineering, Germany Goldmann IOP will be measured at 8am, 10am 2pm and 4pm. Pulse amplitude, similar to Pulsatility Ocular Blood Flow (POBF) will be measured using the Pascal Dynamic Contour Tonometer (DCT) at 8am, 10am, 2pm, and 4 pm.
All procedures will conform to the Declaration of Helsinki and the study will be approved by the Ethics Committee and each patient will sign an informed consent form.
Following visit one, Cosopt will be added to the patients therapy (bid). Following 6 weeks of therapy patients will return for visit two. Cosopt will be applied by the investigator at 8am on visit 2.
We expect that this blood flow will be improved with COSOPT therapy and that the diurnal fluctuation of this parameter will be improved as well. It is evidently of great interest to examine diurnal changes in ocular blood flow with and without COSOPT and the measurement of POBF can be performed without great cost and is well tolerated by the patient.
Changes in IOP, ONH Topography, and ONH blood flow will be analysed using appropriate statistical approaches
- Conditions
- Eye Disease
- Being tested
- Dorzolamide 20 mg and Timolol 5 mg
- Keywords
- Ocular Hypertension, Open Angle Glaucoma
- Medical subject headings
- Eye Diseases, Ocular Hypertension, Glaucoma, Open-Angle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dorzolamide 20 mg and Timolol 5 mgDrug
Also called Cosopt
Twice daily in the affected eye(s)
| Study group | Role | What they receive |
|---|---|---|
| Cosopt | Experimental | Cosopt ('Dorzolamide 20 mg and Timolol 5 mg) bid And Xalatan hs Vs Xalatan hs Alone Receives: Drug: Dorzolamide 20 mg and Timolol 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical evidence for lower diurnal variational Intraocular Pressure
Measured: Six weeks
Secondary outcomes (1)
The Intraocular Pressure, Retinal and choroidal blood flow will be stabilized on Cosopt therapy
Measured: Six weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2009 (estimated)
- Study start4 May 2009
- Primary completion14 Sep 2011
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Eye DiseaseStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maisonneuve-Rosemont Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Mark R. Lesk, Maisonneuve-Rosemont Hospital
- Investigators
- Mark R Lesk, MSc,MD, Principal investigator, Maisonneuve-Rosemont Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00957190
- Sponsor's protocol ID
- 157-00
- Other IDs
- IISP34708
- Acronym
- DIOXXACT
- Status last verified
- Mar 2017
- First submitted
- 4 Aug 2009
- Last updated
- 27 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Hafez AS, Bizzarro RL, Rivard M, Trabut I, Lovasik JV, Kergoat H, Lesk MR. Reproducibility of retinal and optic nerve head perfusion measurements using scanning laser Doppler flowmetry. Ophthalmic Surg Lasers Imaging. 2003 Sep-Oct;34(5):422-32.
PubMed 14509472Yoshida A, Feke GT, Mori F, Nagaoka T, Fujio N, Ogasawara H, Konno S, Mcmeel JW. Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument. Am J Ophthalmol. 2003 Mar;135(3):356-61. doi: 10.1016/s0002-9394(02)01949-9.
PubMed 12614754Lesk MR, Hafez AS, Descovich D. Relationship between central corneal thickness and changes of optic nerve head topography and blood flow after intraocular pressure reduction in open-angle glaucoma and ocular hypertension. Arch Ophthalmol. 2006 Nov;124(11):1568-72. doi: 10.1001/archopht.124.11.1568.
PubMed 17102003Michelson G, Schmauss B. Two dimensional mapping of the perfusion of the retina and optic nerve head. Br J Ophthalmol. 1995 Dec;79(12):1126-32. doi: 10.1136/bjo.79.12.1126.
PubMed 8562550Sehi M, Flanagan JG, Zeng L, Cook RJ, Trope GE. Anterior optic nerve capillary blood flow response to diurnal variation of mean ocular perfusion pressure in early untreated primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4581-7. doi: 10.1167/iovs.05-0209.
PubMed 16303952
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Change in Optic Nerve Head Blood Flow,Optic Nerve Topography and Diurnal Fluctuation of Intraocular Pressure and Pulsatile Ocular Blood Flow in Glaucoma:Cosopt and Xalatan vs Xalatan Alone
- ClinicalTrials.gov ID
- NCT00957190
- Acronym / sponsor ID
- DIOXXACT / 157-00
- Conditions
- Eye Disease
- Keywords
- Ocular Hypertension, Open Angle Glaucoma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Maisonneuve-Rosemont HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 4 May 2009 (actual)
- Primary completion
- 14 Sep 2011 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 12 Aug 2009 (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.
Diurnal and intervisit fluctuations in IOP are strongly associated with progression of open angle glaucoma and therefore need to be minimized. Control of diurnal fluctuations of IOP with different ocular hypotensive medications has been studied in some detail. But how do IOP changes contribute to progressive glaucomatous optic nerve damage? It is reasonable to assume that there are two principal effects of IOP changes. First, IOP fluctuations result in changes in the stresses and strains on the ONH which in turn result in morphological changes to the ONH. These morphological changes could in turn result in stretching and damage to axons of the ONH. Secondly, IOP fluctuations results in changes to the forces acting on the ONH vasculature, leading to changes in ONH vascular perfusion. These changes to perfusion could in turn result in relative ischemia of the ONH and consequent ONH damage.
The investigators propose to monitor diurnal fluctuations in IOP and choroidal blood flow (Pulsatile Ocular Blood Flow,POBF), and intervisit ONH topographical and blood flow changes-ie to monitor the direct ONH consequences of IOP . Open angle glaucoma patients are commonly prescribed topical latanoprost as first line therapy. The EXACCT study, for which I was the principal investigator and which is now submitted for publication, demonstrated that COSOPT was an efficacious choice as second line therapy for patients not controlled on latanoprost monotherapy. The investigators will therefore recruit 20 OAG patients on latanoprost monotherapy, perform diurnal curves of IOP, as well as a.m. ONH morphology and ONH blood flow. Cosopt will then be added and at the next visit the same measurements will be repeated.
The investigators expect that when Cosopt is added the investigators will demonstrate improved IOP, morphology and blood flow compared to the latanoprost baseline. Furthermore the investigators expect the the diurnal fluctuation of IOP and choroidal blood flow will be stabilized on Cosopt therapy. The implications are that adding Cosopt to latanoprost can stabilize not only the IOP but also the damaging consequences of IOP to the optic nerve head.
Detailed description
Twenty patients with open angle glaucoma or ocular hypertension currently on latanoprost immunotherapy will be recruited.
A complete routine ophthalmic examination including biomicroscopy, gonioscopy and fundus ophthalmoscopy will be performed. The eye with better visual acuity is selected for fundus flowmetry.
All patients will undergo a complete diurnal workup including IOP, as well as 10am Confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography-3) of ONH topography. Optic nerve head, nasal and temporal peripapillary retinal blood flow are measured with scanning laser Doppler flowmetry (SLDF; Heidelberg Retinal Flowmeter/Tomograph, SLDF analysis software v3.3, Heidelberg Engineering, Germany Goldmann IOP will be measured at 8am, 10am 2pm and 4pm. Pulse amplitude, similar to Pulsatility Ocular Blood Flow (POBF) will be measured using the Pascal Dynamic Contour Tonometer (DCT) at 8am, 10am, 2pm, and 4 pm.
All procedures will conform to the Declaration of Helsinki and the study will be approved by the Ethics Committee and each patient will sign an informed consent form.
Following visit one, Cosopt will be added to the patients therapy (bid). Following 6 weeks of therapy patients will return for visit two. Cosopt will be applied by the investigator at 8am on visit 2.
We expect that this blood flow will be improved with COSOPT therapy and that the diurnal fluctuation of this parameter will be improved as well. It is evidently of great interest to examine diurnal changes in ocular blood flow with and without COSOPT and the measurement of POBF can be performed without great cost and is well tolerated by the patient.
Changes in IOP, ONH Topography, and ONH blood flow will be analysed using appropriate statistical approaches
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cosopt | Experimental | Drug: Dorzolamide 20 mg and Timolol 5 mgCosopt ('Dorzolamide 20 mg and Timolol 5 mg) bid And Xalatan hs Vs Xalatan hs Alone |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjets with open angle glaucoma or ocular hypertension currently on latanoprost immunotherapy.
- Subjets must have clear media, corrected visual acuity of 6/12 or better,and be able to sit for imaging.
Key exclusion criteria (2 listed)
- Subjets with contraindications or known allergies to any of the components of Cosopt.
- Subjets who had undergoing laser or any ocular surgery.
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 |
|---|---|---|
| Dorzolamide 20 mg and Timolol 5 mgAlso: CosoptTwice daily in the affected eye(s) | Drug | Cosopt |
Primary outcome
Clinical evidence for lower diurnal variational Intraocular Pressure
Time frame: Six weeks
1 secondary outcome
The Intraocular Pressure, Retinal and choroidal blood flow will be stabilized on Cosopt therapy
Time frame: Six 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 27 Mar 2017.
- Results publication: PubMed 14509472Hafez AS, Bizzarro RL, Rivard M, Trabut I, Lovasik JV, Kergoat H, Lesk MR. Reproducibility of retinal and optic nerve head perfusion measurements using scanning laser Doppler flowmetry. Ophthalmic Surg Lasers Imaging. 2003 Sep-Oct;34(5):422-32.
- Results publication: PubMed 12614754Yoshida A, Feke GT, Mori F, Nagaoka T, Fujio N, Ogasawara H, Konno S, Mcmeel JW. Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument. Am J Ophthalmol. 2003 Mar;135(3):356-61. doi: 10.1016/s0002-9394(02)01949-9.
- Results publication: PubMed 17102003Lesk MR, Hafez AS, Descovich D. Relationship between central corneal thickness and changes of optic nerve head topography and blood flow after intraocular pressure reduction in open-angle glaucoma and ocular hypertension. Arch Ophthalmol. 2006 Nov;124(11):1568-72. doi: 10.1001/archopht.124.11.1568.
- Results publication: PubMed 8562550Michelson G, Schmauss B. Two dimensional mapping of the perfusion of the retina and optic nerve head. Br J Ophthalmol. 1995 Dec;79(12):1126-32. doi: 10.1136/bjo.79.12.1126.
- Results publication: PubMed 16303952Sehi M, Flanagan JG, Zeng L, Cook RJ, Trope GE. Anterior optic nerve capillary blood flow response to diurnal variation of mean ocular perfusion pressure in early untreated primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4581-7. doi: 10.1167/iovs.05-0209.
- 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.
Mark R Lesk, MSc,MD principal investigator
Maisonneuve-Rosemont Hospital
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 Dorzolamide 20 mg and Timolol 5 mg in people with Eye Disease, run by Maisonneuve-Rosemont Hospital at 1 site in Canada.
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 2 inclusion and 2 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 Mar 2017. 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 Canada. 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?
Clinical evidence for lower diurnal variational Intraocular Pressure (time frame: Six weeks). 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 NCT00957190, which also lists 5 linked publications.
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 Mar 2017.