Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions (Myoc Gene)
|Glaucoma||Drug: Cosopt (combination eyedrop of dorzolamide and timolol)||Phase 4|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
|Official Title:||The Effect of Myocilin Genetic Variants on Intraocular Pressure and Blood Pressure Variation in Sitting and Supine Positions.|
- Intraocular Pressure in Sitting and Supine Positions. [ Time Frame: 10 weeks ]Effect of Cosopt treatment on intraocular pressure changes in sitting to supine positions.
- Blood Pressure in Sitting to Supine Positions [ Time Frame: 10 weeks ]Effect of Cosopt treatment on blood pressure changes in sitting to supine positions.
- Myocilin Mutation Arg272Gly in Subjects [ Time Frame: 10 week study ]Number of subjects with Myocilin Arg272Gly
|Actual Study Start Date:||August 4, 2009|
|Study Completion Date:||July 18, 2012|
|Primary Completion Date:||July 18, 2012 (Final data collection date for primary outcome measure)|
Intraocular pressure and blood pressure measurements will be compared under the following conditions: 1) after washout of clinical treatment, 2) after treatment with Cosopt, and 3) after another washout of Cosopt.
Drug: Cosopt (combination eyedrop of dorzolamide and timolol)
One drop in each eye every twelve hours for six weeks
Other Name: Cosopt
Glaucoma is an important public health issue, and identifying new markers to improve treatment outcomes is a high priority. Progress in Mendelian genetic approaches has led to identifying 15 genes and 31 loci (http://www.ncbi.nlm.nih.gov/); however, since these monogenic forms of glaucoma are uncommon, other approaches are needed to identify genetic markers that contribute to common risk factors, such as elevated eye pressure, eye pressure fluctuation, and drug response variation.
It is well known that eye pressure varies over a 24-hour period,1-6 but the mechanisms that regulate this eye pressure rhythm are not yet fully known. Drance reported that 84% of normal eyes (N=320 eyes) had eye pressure fluctuations of less than 5 mmHg in contrast to only 6% of untreated glaucomatous eyes (N=138).7 Drance clearly recognized that eye pressure factors were more variable in eyes with glaucoma. Attention to this eye pressure fluctuation during glaucoma treatment is important because fluctuation leads to progression. The variation in eye pressure drug response profiles measured at selected times over a 24-hour period is related to the mechanism of action of these drugs, endogenous circadian rhythms, and glaucoma. The molecular and genetic tools are now available to identify potential genetic markers for these variable traits.
Advancing clinical research to the "translational" level is an important step to integrate our ever increasing knowledge base in genomics and proteinomics with clinical trials and clinical studies. Given the infrastructure at the University of Michigan with the strength in both glaucoma genetics and our resources in the clinic, it is possible to test for relationships between glaucoma genes and eye pressure. Although it is known that myocilin (MYOC) mutations cause the phenotype of high pressure open-angle glaucoma, the effect of these MYOC mutations in "pre-symptomatic" subjects and patients with early open-angle glaucoma on eye pressure variation is not known.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00906087
|United States, Michigan|
|W.K. Kellogg Eye Center|
|Ann Arbor, Michigan, United States, 48105|
|Principal Investigator:||Sayoko E Moroi, MD, PhD||University of Michigan Department of Ophthalmology and Visual Sciences|