Circadian Rhythms of Aqueous Humor Dynamics in Humans
|ClinicalTrials.gov Identifier: NCT00572936|
Recruitment Status : Completed
First Posted : December 13, 2007
Results First Posted : February 14, 2018
Last Update Posted : February 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Glaucoma||Drug: Latanoprost Drug: Dorzolamide Drug: Timolol||Phase 2|
Glaucoma is a progressive optic neuropathy and a leading cause of blindness in the United States. In glaucoma, vision is lost through apoptosis (programmed cell death) of retinal ganglion cells, a type of cell in the retina that transmits visual information to the brain. Diagnosis of glaucoma is usually based on a combination of progressive, characteristic vision loss (measured using visual field testing) and progressive optic nerve head damage (as detected through dilated fundus examinations or disc photography). While a high pressure inside the eye (ocular hypertension, OHT) is not sufficient for a diagnosis of glaucoma, it is the greatest single risk factor for disease onset.
Currently, the only effective treatment to prevent disease progression is lowering of the intraocular pressure (IOP). IOP is determined by the balance between aqueous production (flow) and aqueous outflow through either the trabecular meshwork or uveoscleral pathway. Diurnal rhythms in aqueous humor dynamics and nocturnal fluctuations in IOP and aqueous flow have been studied in some detail9 but little is known about the nocturnal rhythms of aqueous humor outflow.
Usually, clinical IOP measurement is performed during the day; little is known about nocturnal IOP fluctuations in relation to glaucoma management . A recent surge of interest in nocturnal IOPs stems from the hypothesis that significant glaucomatous damage may occur at night. In response, some investigators have advocated particular classes of glaucoma medications based on their nocturnal IOP effects. 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.
Additionally, previous research on glaucoma medications has been limited to the effects ocular hypotensive drugs on 24-hour IOP or daytime aqueous humor dynamics; few studies have addressed their effect on nocturnal aqueous humor dynamics. Beta-blockers have been proven effective in lowering IOP during the day by decreasing aqueous flow. However, limitations have been found in their IOP-lowering effect overnight. Prostaglandins, which increase uveoscleral outflow, seem to possess a hypotensive effect that is constant throughout the 24-hour period. Dorzolamide reduces aqueous flow to lower IOP but few studies have addressed its effect at night. This study is designed to elucidate the physiological mechanisms driving the efficacy of these drugs throughout the 24-hour period, i.e. circadian rhythms in aqueous humor dynamics.
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 each of the glaucoma drugs affects aqueous humor dynamics in different ways, it is essential that no residual medical effect remains from these drugs. Standard washout periods of 6-weeks will be utilized in between drug assessments. This period of time is based on the methods of other published studies which determined a necessary period of 4-8 weeks for ocular washout of prostaglandins. A concern for patient safety exists when OHT patients are taken off of glaucoma medications, as IOP may rise during the washout. In order to monitor IOP in these patients, most study methods utilize a biweekly check of the IOP. If pressure rises above the ophthalmologist's preset "target pressure" at any point, then the patient is removed from the study and returned to their previous medical regimen.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||Circadian Rhythms of Aqueous Humor Dynamics in Humans|
|Study Start Date :||November 2005|
|Actual Primary Completion Date :||November 2009|
|Actual Study Completion Date :||November 2009|
The participants received latanoprost at night and vehicle in the morning for two weeks, then 6 week washout, then Dorzolamide BID for two weeks, then 6 week washout, then Timolol BID for two weeks. The order in which the participants received the three different drugs was random.
Other Name: xalatanDrug: Dorzolamide
carbonic anhydrase inhibitor
Other Name: trusoptDrug: Timolol
Other Name: Timoptic, Betimol, Timoptic-xe, Istalol, Timoptic Ocudose
- Intraocular Pressure [ Time Frame: 2 weeks ]Intra-ocular Pressure was measured by applanation tonometry
- Aqueous Flow [ Time Frame: 2 weeks ]aqueous flow measurements was calculated using fluorophotometry measurements.
- Central Corneal Thickness [ Time Frame: 2 weeks ]central corneal thickness was measured by ultrasound pachymetry
- Anterior Chamber Volume [ Time Frame: 2 weeks ]Anterior chamber volume was measured by A-scan ultrasound biometry, daytime
- Blood Pressure [ Time Frame: 2 weeks ]blood pressure was measured by sphygmomanometry
- Episcleral Venous Pressure [ Time Frame: 2 weeks ]Episcleral venous pressure was measured by venomenometry
- Outflow Facility [ Time Frame: 2 weeks ]outflow facility was calculated using fluorophotometry and tonography
- Uvescleral Outflow [ Time Frame: 2 weeks ]uvescleral outflow was calulated using goldmann equation
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00572936
|United States, Nebraska|
|UNMC Department of Ophthalmolgy and Visual Sciences|
|Omaha, Nebraska, United States, 68198-5540|
|Principal Investigator:||Carl B Camras, MD||University of Nebraska|