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

NCT00957190 | Completed Phase 4 DMC

• 2 other identifiers: 157-00IISP34708
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Eye Disease

Keywords

Ocular Hypertension; Open Angle Glaucoma

Outcome Measures

Primary Outcomes (1)

• Clinical evidence for lower diurnal variational Intraocular Pressure

  Six weeks

Secondary Outcomes (1)

• The Intraocular Pressure, Retinal and choroidal blood flow will be stabilized on Cosopt therapy

  Six weeks

Study Arms (1)

Cosopt

EXPERIMENTAL

Cosopt ('Dorzolamide 20 mg and Timolol 5 mg) bid And Xalatan hs Vs Xalatan hs Alone

Drug: Dorzolamide 20 mg and Timolol 5 mg

Interventions

Dorzolamide 20 mg and Timolol 5 mg DRUG

Twice daily in the affected eye(s)

Also known as: Cosopt

Cosopt

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Subjets with contraindications or known allergies to any of the components of Cosopt.
• Subjets who had undergoing laser or any ocular surgery.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (5)

• 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.

  PMID: 14509472 RESULT

• Yoshida 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.

  PMID: 12614754 RESULT

• Lesk 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.

  PMID: 17102003 RESULT

• Michelson 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.

  PMID: 8562550 RESULT

• Sehi 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.

  PMID: 16303952 RESULT

MeSH Terms

Conditions

Eye Diseases; Ocular Hypertension; Glaucoma, Open-Angle

Interventions

dorzolamide; Timolol; dorzolamide-timolol combination

Condition Hierarchy (Ancestors)

Glaucoma

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines

Study Officials

• Mark R Lesk, MSc,MD

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of opthalmology research

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 12, 2009
• Study Start: May 4, 2009
• Primary Completion: September 14, 2011
• Study Completion: February 1, 2012
• Last Updated: March 27, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)