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

Primary Purpose

Glaucoma

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Cosopt (combination eyedrop of dorzolamide and timolol)
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Glaucoma focused on measuring Myocilin gene, Glaucoma, dorzolamide and timolol combination eyedrop

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • W.K. Kellogg Eye Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Cosopt

Arm Description

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.

Outcomes

Primary Outcome Measures

Intraocular Pressure in Sitting and Supine Positions.
Effect of Cosopt treatment on intraocular pressure changes in sitting to supine positions.
Blood Pressure in Sitting to Supine Positions
Effect of Cosopt treatment on blood pressure changes in sitting to supine positions.

Secondary Outcome Measures

Myocilin Mutation Arg272Gly in Subjects
Number of subjects with Myocilin Arg272Gly

Full Information

First Posted
May 19, 2009
Last Updated
May 2, 2017
Sponsor
University of Michigan
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00906087
Brief Title
Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions
Acronym
Myoc Gene
Official Title
The Effect of Myocilin Genetic Variants on Intraocular Pressure and Blood Pressure Variation in Sitting and Supine Positions.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 4, 2009 (Actual)
Primary Completion Date
July 18, 2012 (Actual)
Study Completion Date
July 18, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma
Keywords
Myocilin gene, Glaucoma, dorzolamide and timolol combination eyedrop

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cosopt
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cosopt (combination eyedrop of dorzolamide and timolol)
Other Intervention Name(s)
Cosopt
Intervention Description
One drop in each eye every twelve hours for six weeks
Primary Outcome Measure Information:
Title
Intraocular Pressure in Sitting and Supine Positions.
Description
Effect of Cosopt treatment on intraocular pressure changes in sitting to supine positions.
Time Frame
10 weeks
Title
Blood Pressure in Sitting to Supine Positions
Description
Effect of Cosopt treatment on blood pressure changes in sitting to supine positions.
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Myocilin Mutation Arg272Gly in Subjects
Description
Number of subjects with Myocilin Arg272Gly
Time Frame
10 week study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sayoko E Moroi, MD, PhD
Organizational Affiliation
University of Michigan Department of Ophthalmology and Visual Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
W.K. Kellogg Eye Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States

12. IPD Sharing Statement

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Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions

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