Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions (Myoc Gene)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by University of Michigan.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00906087
First received: May 19, 2009
Last updated: May 22, 2009
Last verified: May 2009

May 19, 2009
May 22, 2009
May 2009
July 2010   (final data collection date for primary outcome measure)
To determine if the myocilin gene which can cause glaucoma affects eye and blood pressure changes in sitting and supine positions with and without glaucoma drug (Cosopt eyedrop specifically) treatment. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00906087 on ClinicalTrials.gov Archive Site
Blood pressure and eye pressure changes with and without treatment in sitting and supine positions [ Time Frame: 10 week study ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions
The Effect of Myocilin Genetic Variants on Intraocular Pressure and Blood Pressure Variation in Sitting and Supine Positions.

The purpose of this study is to determine if one of the genes that can cause glaucoma, called myocilin, are associated with larger eye pressure and blood pressure changes in sitting and lying down positions without glaucoma drug treatment and with glaucoma drug treatment with a combination medication called Cosopt® (Merck & Co., Inc.).

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 IOP, IOP fluctuation, and drug response variation.

It is well known that IOP varies over a 24-hour period,1-6 but the mechanisms that regulate this IOP rhythm are not yet fully known. Drance reported that 84% of normal eyes (N=320 eyes) had IOP fluctuations of less than 5 mmHg in contrast to only 6% of untreated glaucomatous eyes (N=138).7 Drance clearly recognized that IOP factors were more variable in eyes with glaucoma. Attention to this IOP fluctuation during glaucoma treatment is important because fluctuation leads to progression. The variation in IOP 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. We now have the molecular and genomic tools 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, we are well-positioned to conduct such translational research in glaucoma. Although it is known that myocilin (MYOC) mutations cause the phenotype of high pressure open-angle glaucoma (OAG), the effect of these MYOC mutations in "pre-symptomatic" subjects and patients with early OAG on IOP variation is not known.

Interventional
Phase 4
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Glaucoma
Drug: Cosopt (combination eyedrop of dorzolamide and timolol)
One drop in each eye every twelve hours for six weeks
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
July 2010
July 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Early OAG, as determined by a comprehensive ophthalmic examination
  • Greater than or equal to 18 years of age
  • Either gender
  • Any race
  • Both eyes meet eligibility criteria
  • Cup to disc ratio less than 0.8 determined by fundoscopy and confirmed by disc photos
  • Visual field parameters in the study eye: Pattern Standard Deviation (PSD) greater than 1.0 dB but less than 6.0 dB
  • Ability to cooperate for an outpatient study involving at least five visits over a four month study period
  • Ability to comply with Cosopt treatment regimen

Exclusion Criteria:

  • Less than or equal to 18 years old
  • Refusal to be genotyped or sign Informed Consent for Protocol 1991-144
  • Pregnant or lactating women
  • Medical conditions of severe pulmonary compromise with asthma or emphysema or cardiac contraindications to beta-blockers
  • Ocular disease of chronic angle-closure glaucoma, iridocorneal endothelial disease, posterior polymorphous corneal dystrophy, epithelial downgrowth, uveitic glaucoma, or neovascular glaucoma
  • Ocular surgery for glaucoma, including trabeculectomy, other glaucoma filtration surgery, glaucoma drainage implant, or laser cyclophotocoagulation
  • Current use of systemic steroids or chemotherapeutic agents that non-selectively inhibit dividing cells
  • Proliferative diabetic retinopathy, history of panretinal photocoagulation treatment, diabetic macular edema, or history of macular grid laser treatment
  • History of changing treatment involving the use oral beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, or oral alpha 2-agonists in the prior two months or in the next month (i.e., must be on stable treatment with any of these drugs for at least two months)
  • Patients taking erectile dysfunction drugs (i.e., Viagra, Cialis, Levitra)
  • Contradictions:

    • bronchial asthma or a history of bronchial asthma
    • severe chronic obstructive pulmonary disease
    • sinus bradycardia
    • second or third degree atrioventricular block
    • overt cardiac failure
    • cardiogenic shock
    • hypersensitivity to any component of Cosopt
Both
18 Years and older
No
Contact: Carol J Pollack-Rundle, BS, COMT 7349369805 cjrundle@med.umich.edu
Contact: Sayoko E Moroi, MD 7347635874
United States
 
NCT00906087
Merck IISP#31911, Merck IISP#31911
Yes
Sayoko Moroi, MD, PhD, University of Michigan Department of Ophthalmology and Visual Science
University of Michigan
Merck
Principal Investigator: Sayoko E Moroi, MD, PhD University of Michigan Department of Ophthalmology and Visual Sciences
University of Michigan
May 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP