Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients

NCT02053298 | Completed Phase 4

• 1 other identifier: S - 54854
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Open Angle Glaucoma

Keywords

Glaucoma

Outcome Measures

Primary Outcomes (1)

• 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%

  2 months

Study Arms (1)

Timolol & Dorzolamide

EXPERIMENTAL

Topical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month

Drug: Timolol & Dorzolamide

Interventions

Timolol & Dorzolamide DRUG

Topical preservative-free fixed combination of timolol 0.5%+dorzolamide 2% to be applied bid for 1 month

Also known as: Cosopt UD

Timolol & Dorzolamide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Flemish Brabant, 3000 Leuven, Belgium

Location

Related Publications (1)

• 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.

  PMID: 22268445 BACKGROUND

MeSH Terms

Conditions

Glaucoma, Open-Angle; Glaucoma

Interventions

dorzolamide-timolol combination

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Study Officials

• Ingeborg Stalmans, MD, PhD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2014
• First Posted: February 3, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

BE (1)