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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Carol B. Toris, BA MS PhD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01342419
First received: April 25, 2011
Last updated: June 13, 2012
Last verified: June 2012
  Purpose

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
Glaucoma Suspects

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Official Title: Circadian Rhythms of Aqueous Humor Dynamics When Using Brimonidine in Humans With Ocular Hypertension

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Enrollment: 35
Study Start Date: August 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with intraocular pressure between 21 - 35 mmHg

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.
  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: NCT01342419

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

No publications provided

Responsible Party: Carol B. Toris, BA MS PhD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01342419     History of Changes
Other Study ID Numbers: 22010
Study First Received: April 25, 2011
Last Updated: June 13, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hypertension
Ocular Hypertension
Vascular Diseases
Cardiovascular Diseases
Eye Diseases
Brimonidine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014