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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sayoko E. Moroi, University of Michigan
ClinicalTrials.gov Identifier:
NCT00906087
First received: May 19, 2009
Last updated: December 16, 2013
Last verified: December 2013
  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: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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 University of Michigan:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 14
Study Start Date: May 2009
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cosopt
Cosopt 1 drop two times daily was administered for 6 weeks.
Drug: Cosopt (combination eyedrop of dorzolamide and timolol)
One drop in each eye every twelve hours for six weeks
Other Name: Cosopt
No Intervention: No glaucoma medication.
After appropriate washout, no glaucoma medication was administered for 6 weeks.

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

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
Study First Received: May 19, 2009
Last Updated: December 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Myocilin gene
Glaucoma
dorzolamide and timolol combination eyedrop

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

ClinicalTrials.gov processed this record on April 16, 2014