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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00906087
First Posted: May 21, 2009
Last Update Posted: June 2, 2017
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.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sayoko E. Moroi, University of Michigan
  Purpose
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.).

Condition Intervention Phase
Glaucoma Drug: Cosopt (combination eyedrop of dorzolamide and timolol) Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Sayoko E. Moroi, University of Michigan:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Myocilin Mutation Arg272Gly in Subjects [ Time Frame: 10 week study ]
    Number of subjects with Myocilin Arg272Gly


Enrollment: 14
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)
Arms Assigned Interventions
Cosopt
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

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00906087


Locations
United States, Michigan
W.K. Kellogg Eye Center
Ann Arbor, Michigan, United States, 48105
Sponsors and Collaborators
University of Michigan
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Sayoko E Moroi, MD, PhD University of Michigan Department of Ophthalmology and Visual Sciences
  More Information

Responsible Party: Sayoko E. Moroi, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT00906087     History of Changes
Other Study ID Numbers: Merck IISP#31911
Merck IISP#31911 ( Other Grant/Funding Number: Merck )
First Submitted: May 19, 2009
First Posted: May 21, 2009
Results First Submitted: March 17, 2017
Results First Posted: June 2, 2017
Last Update Posted: June 2, 2017
Last Verified: May 2017

Keywords provided by Sayoko E. Moroi, University of Michigan:
Myocilin gene
Glaucoma
dorzolamide and timolol combination eyedrop

Additional relevant MeSH terms:
Glaucoma
Ocular Hypertension
Eye Diseases
Timolol
Dorzolamide
Ophthalmic Solutions
Tetrahydrozoline
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Pharmaceutical Solutions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nasal Decongestants
Vasoconstrictor Agents
Respiratory System Agents
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors