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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01342419
Recruitment Status : Completed
First Posted : April 27, 2011
Last Update Posted : June 14, 2012
Information provided by (Responsible Party):
Carol B. Toris, BA MS PhD, University of Nebraska

Brief Summary:
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.

Condition or disease
Glaucoma Suspects

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.

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Study Type : Observational
Actual Enrollment : 35 participants
Observational Model: Case-Crossover
Official Title: Circadian Rhythms of Aqueous Humor Dynamics When Using Brimonidine in Humans With Ocular Hypertension
Study Start Date : August 2010
Actual Primary Completion Date : October 2011
Actual Study Completion Date : October 2011

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with intraocular pressure between 21 - 35 mmHg

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01342419

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United States, Nebraska
University of Nebraska Medical Center, Department of Ophthalmology
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
University of Nebraska
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Principal Investigator: Carol Toris, PhD UNMC Department of Ophthalmology and Visual Sciences

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Responsible Party: Carol B. Toris, BA MS PhD, Principal Investigator, University of Nebraska Identifier: NCT01342419     History of Changes
Other Study ID Numbers: 22010
First Posted: April 27, 2011    Key Record Dates
Last Update Posted: June 14, 2012
Last Verified: June 2012
Additional relevant MeSH terms:
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Brimonidine Tartrate
Ocular Hypertension
Vascular Diseases
Cardiovascular Diseases
Eye Diseases
Antihypertensive Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs