Circadian Rhythms of Aqueous Humor Dynamics When Using Brimonidine in Humans With Ocular Hypertension

Condition(s) targeted: Glaucoma Suspects

Phase: N/A

Status: Completed

Sponsored by: University of Nebraska

Official(s) and/or principal investigator(s):
Carol Toris, PhD, Principal Investigator, Affiliation: UNMC Department of Ophthalmology and Visual Sciences

This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine.

Official title: Circadian Rhythms of Aqueous Humor Dynamics When Using Brimonidine in Humans With Ocular Hypertension

Study design: Observational Model: Case-Crossover

Detailed description: Currently, the only effective treatment to prevent disease progression is lowering of the intraocular pressure (IOP).2 Usually, clinical IOP measurements are performed during the day with little information collected on nocturnal IOP. A recent surge of interest in nocturnal IOPs stems from the hypothesis that significant glaucomatous damage may occur at night. 4,5 In response, some investigators have advocated particular classes of glaucoma medications based on their nocturnal IOP effects. 6-8 The most efficacious drug on the market may not be the preferred treatment if it is ineffective at night. Therefore, the understanding of nighttime IOP and the aqueous humor dynamics that control it has important scientific, clinical, and commercial implications. Previous research on glaucoma medications has been limited to the effects of ocular hypotensive drugs on 24-hour IOP or daytime aqueous humor dynamics. Few studies have evaluated nocturnal aqueous humor dynamics. The investigators recently completed studies of day and night differences in aqueous humor dynamics in patients treated with drugs from three different classes that include a prostaglandin analog, a beta blocker and a carbonic anhydrase inhibitor. The current study is designed to elucidate the physiological mechanisms driving the efficacy of brimonidine, an alpha 2 adrenergic agonist, throughout the 24-hour period, i. e. circadian rhythms in aqueous humor dynamics. Based on what the investigators know of 24 hour IOPs this drug is expected to work well at night potentially by enhancing uveoscleral outflow. This study will test this hypothesis. In studies of new glaucoma medications the preferred study population includes ocular hypertensive subjects. These people have high IOP but no optic nerve damage and no glaucoma. They may be taking prescribed IOP lowering drugs for this condition or they may not. Those taking ocular drugs are asked to stop taking them. Since glaucoma drugs affect aqueous humor dynamics in different ways, it is essential that no residual medical effect remains from these drugs. A washout period is necessary to remove all topical ocular drug effects. A concern for patient safety exists when OHT patients are taken off of glaucoma medications, as IOP may rise during the washout period. In order to monitor IOP in these patients, a biweekly check of the IOP is made. If pressure rises above the ophthalmologist's preset "target pressure" at any point, then the patient is removed from the study and returned to his/her previous medical regimen.

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- History of untreated intraocular pressure (IOO) between 21 and 35 mmHg

- 19 years of age and older

Exclusion Criteria:

- Pregnant or nursing

- Aphakia or pseudophakia

- Best corrected visual acuity worse than 20/60 in either eye

- Chronic or recurrent severe ocular inflammatory disease

- Ocular infection or inflammation within (3 months of screening visit

- History of clinically significant or progressive retinal disease such as retinal

degeneration, diabetic retinopathy or retinal detachment

- Any abnormality preventing reliable tonometry of either eye

- History of any severe ocular pathology or serious hypersensitivity to (including

severe dry eye) that would preclude the administration of a topical Brimonidine or its vehicle.

- Any eye with a cup-to-disc ratio greater than 0. 8

- History of intraocular surgery

- History of laser surgery

- History of severe, unstable, or uncontrolled cardiovascular, hepatic or renal disease

- Less than one month (Prior to baseline) stable dosing regimen of any non-glaucoma

medication that would affect IOP.

- Gonioscopy angle <2

- Inability to discontinue contact lens wear.

- Therapy with any investigational agent within 30 days of screening.

- Use of any additional topical or systemic adjunctive ocular hypotensive medications

during the study.

- History of open angle glaucoma (either primary open angle glaucoma or other cause of

open angle glaucoma) or narrow angle glaucoma.

University of Nebraska Medical Center, Department of Ophthalmology, Omaha, Nebraska 68198, United States

Starting date: August 2010
Last updated: June 13, 2012