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

Glaucoma Clinical Trial

— Myoc Gene  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00906087
• Other study ID #: Merck IISP#31911
• Secondary ID: Merck IISP#31911
• Status: Completed
• Phase: Phase 4
• First received: May 19, 2009
• Last updated: May 17, 2016
• Start date: May 2009

Study information

• Verified date: May 2016
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Glaucoma

Intervention

Drug:
• Cosopt (combination eyedrop of dorzolamide and timolol)
One drop in each eye every twelve hours for six weeks

Locations

Country	Name	City	State
United States	W.K. Kellogg Eye Center	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		10 weeks	No
Secondary	Blood pressure and eye pressure changes with and without treatment in sitting and supine positions		10 week study	No