Circadian Ocular Perfusion Pressure and Ocular Blood Flow

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alcon Research
ClinicalTrials.gov Identifier:
NCT00800540
First received: December 1, 2008
Last updated: March 20, 2013
Last verified: March 2013
  Purpose

The purpose of this study was to compare the short term effects of two intraocular pressure (IOP) lowering medications on ocular perfusion pressure (OPP), ocular blood flow, intraocular pressure, and blood pressure in patients with glaucoma. Ocular perfusion pressure (OPP) is defined as the difference between arterial blood pressure (diastolic and systolic) and intraocular pressure. The primary efficacy assessment is based on diastolic ocular perfusion pressure.


Condition Intervention Phase
Glaucoma
Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension
Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Topical Hypotensive Drugs on Circadian Ocular Perfusion Pressure and Ocular Blood Flow in Patients With Open-Angle Glaucoma

Resource links provided by NLM:


Further study details as provided by Alcon Research:

Primary Outcome Measures:
  • Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Diastolic ocular perfusion pressure (DOPP) is defined as the difference between diastolic arterial pressure and intraocular pressure. Diastolic arterial pressure was measured with a calibrated automated sphygmomanometer. Intraocular pressure was measured with a calibrated pneumatonometer. A lower DOPP indicates a lower optic blood supply, which can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).


Secondary Outcome Measures:
  • Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Circadian diastolic ocular perfusion pressure (COPP) is defined as the variations in diastolic OPP during the day and night. Diastolic ocular perfusion pressure was calculated at 7 timepoints over a 24-hour period. Changes in the diastolic ocular perfusion pressure rhythm throughout the day (outside the normal range) may affect glaucoma progression.

  • Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression.

  • Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression.

  • Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Intraocular pressure (IOP) is defined as the fluid pressure inside the eye. Intraocular pressure was measured with a calibrated pneumatonometer at 7 time points over a 24-hour period. High IOP (outside the normal range) can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).

  • Mean Change From Baseline in Diastolic Blood Pressure at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Diastolic blood pressure refers to the minimum pressure, that is, the pressure between heartbeats. Diastolic glood pressure was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting.

  • Mean Change From Baseline in Systolic Blood Pressure at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Systolic blood pressure refers to the maximum pressure, that is, the pressure while the heart is beating, and was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting.

  • Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Vascular resistance in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.

  • Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Vascular resistance in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.

  • Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    End diastolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.

  • Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Peak systolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.

  • Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 [ Time Frame: Week 0, Week 6 (period-based) ] [ Designated as safety issue: No ]
    Peak systolic velocity in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.


Enrollment: 35
Study Start Date: February 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
AZARGA/COMBIGAN
AZARGA, followed by COMBIGAN, as randomized. Each fixed combination instilled in the study eye, one drop twice daily (9:00 and 21:00), for six weeks, with a 4-week washout period separating the two treatment periods.
Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension
Fixed combination ophthalmic suspension
Other Name: AZARGA™
Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution
Fixed combination ophthalmic solution
Other Name: COMBIGAN®
COMBIGAN/AZARGA
COMBIGAN, followed by AZARGA, as randomized. Each fixed combination instilled in the study eye, one drop twice daily (9:00 and 21:00), for six weeks, with a 4-week washout period separating the two treatment periods.
Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension
Fixed combination ophthalmic suspension
Other Name: AZARGA™
Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution
Fixed combination ophthalmic solution
Other Name: COMBIGAN®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Sign Informed Consent.
  • Diagnosis of open-angle glaucoma in at least one eye.
  • Requires more than one IOP-lowering medication.
  • IOP measurements at Screening, Safety, and Eligibility/Period 1 Baseline Visits as specified in protocol.
  • Able to discontinue all IOP-lowering medication prior to Eligibility Visit and for 4 weeks between treatment periods.
  • Willing to complete all required study visits.
  • Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

  • Female of child-bearing potential if pregnant, lactating, or not using highly effective birth control measures.
  • Severe central visual field loss in either eye.
  • Previous glaucoma surgery in the study eye.
  • Intraocular surgery in the study eye within 3 months prior to the Screening Visit.
  • Wears contact lenses.
  • Allergy/hypersensitivity to study medication.
  • Cannot safely discontinue use of glucocorticoid medication.
  • Uses medication that could affect IOP or blood pressure.
  • Recent use of high-dose aspirin.
  • Bronchial asthma or severe chronic obstructive pulmonary disease.
  • Diabetic retinopathy.
  • Any abnormality preventing reliable tonometry.
  • Any severe illness or condition unsuitable for the study, in the opinion of the investigator.
  • Other protocol-defined exclusion criteria may apply.
  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: NCT00800540

Locations
United States, Texas
Contact Alcon Call Center at 1-888-451-3937 For Trial Locations
Fort Worth, Texas, United States, 76134
Sponsors and Collaborators
Alcon Research
  More Information

No publications provided

Responsible Party: Alcon Research
ClinicalTrials.gov Identifier: NCT00800540     History of Changes
Other Study ID Numbers: C-07-16, 2007-005936-99
Study First Received: December 1, 2008
Results First Received: January 31, 2013
Last Updated: March 20, 2013
Health Authority: Greece: Ethics Committee

Keywords provided by Alcon Research:
glaucoma
ocular perfusion pressure
ocular blood flow
open angle glaucoma requiring more than one IOP-lowering medication

Additional relevant MeSH terms:
Glaucoma
Glaucoma, Open-Angle
Ocular Hypertension
Eye Diseases
Tetrahydrozoline
Ophthalmic Solutions
Timolol
Brinzolamide
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Respiratory System Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Antihypertensive Agents
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014