Effect of Myocilin Genetic Variants on Intraocular Pressure and Pressure Variation in Sitting and Supine Positions (Myoc Gene)
Recruitment status was Recruiting
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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: | 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. |
- 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 ]
- 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 ]
| Estimated Enrollment: | 20 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | July 2010 |
| Estimated Primary Completion Date: | July 2010 (Final data collection date for primary outcome measure) |
-
Drug: Cosopt (combination eyedrop of dorzolamide and timolol)
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 |
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| Contact: Carol J Pollack-Rundle, BS, COMT | 7349369805 | cjrundle@med.umich.edu |
| Contact: Sayoko E Moroi, MD | 7347635874 |
| United States, Michigan | |
| W.K. Kellogg Eye Center | Recruiting |
| Ann Arbor, Michigan, United States, 48105 | |
| Contact: Carol J Pollack-Rundle, BS, COMT 734-936-9805 | |
| Principal Investigator: Sayoko E Moroi, MD, PhD | |
| Principal Investigator: | Sayoko E Moroi, MD, PhD | University of Michigan Department of Ophthalmology and Visual Sciences |
More Information
No publications provided
| Responsible Party: | Sayoko Moroi, MD, PhD, University of Michigan Department of Ophthalmology and Visual Science |
| 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: | May 22, 2009 |
| 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 May 16, 2013