The DIOXXACT Trial(Diurnal IOP and OBF Xalatan vs Xalatan And Cosopt Trial)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier:
NCT00957190
First received: August 4, 2009
Last updated: August 11, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Eye Disease
Drug: Dorzolamide 20 mg and Timolol 5 mg
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Maisonneuve-Rosemont Hospital:

Primary Outcome Measures:
  • Clinical evidence for lower diurnal variational Intraocular Pressure [ Time Frame: Six weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Intraocular Pressure, Retinal and choroidal blood flow will be stabilized on Cosopt therapy [ Time Frame: Six weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: June 2009
Estimated Study Completion Date: September 2010
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cosopt
Cosopt And Xalatan Vs Xalatan Alone
Drug: Dorzolamide 20 mg and Timolol 5 mg
Twice daily in the affected eye(s)

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

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Subjets with contraindications or known allergies to any of the components of Cosopt.
  • Subjets who had undergoing laser or any ocular surgery.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00957190

Locations
Canada, Quebec
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Sponsors and Collaborators
Maisonneuve-Rosemont Hospital
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Mark R Lesk, MSc,MD Maisonneuve-Rosemont Hospital
  More Information

Publications:
Responsible Party: Mark R Lesk, MSc,MD, Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier: NCT00957190     History of Changes
Other Study ID Numbers: 157-00, IISP34708
Study First Received: August 4, 2009
Last Updated: August 11, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Maisonneuve-Rosemont Hospital:
Ocular Hypertension
Open Angle Glaucoma

Additional relevant MeSH terms:
Eye Diseases

ClinicalTrials.gov processed this record on October 20, 2014