Genetics and Markers of Degenerative and Inflammatory Eye Diseases

NCT ID: NCT00647439

Last Updated: 2018-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

609 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-03-27

Study Completion Date

2018-12-04

Brief Summary

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This study will identify genes that are associated with inflammation or degeneration of the retina (membrane lining the back of the eye that relays vision signals to the brain). It is thought that many retinal conditions are due to an altered immune system and are based on how the person s genes function and communicate.

People 4 years of age or older who have a retinal condition such as uveitis, age-related macular degeneration or diabetic retinopathy may be eligible for this study. Healthy volunteers and healthy people who have a family member with one of these conditions are also eligible. Patients with inherited retinal degeneration are excluded.

Participants undergo the following tests and procedures:

* Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine the pupils, lenses, retina and eye movements. Photographs of the inside of the eye may also be taken. The pupils are dilated with drops for this examination.
* Blood draw for genetic testing.

Participants may also undergo one or more of the following tests:

* Optical coherence tomography. This is a type of photograph of the back of the eye to measure thickness of the retina.
* Fluorescein angiography and indocyanine green angiography. Pictures of the eye s blood vessels are taken using either a fluorescein or indocyanine green dye. The dye is injected into a vein in an arm and travels to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels.
* Electroretinogram (ERG) to measure retinal function. The patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small metal disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient then watches flashing lights. The contact lenses sense small electrical signals generated by the retina when the light flashes....

Detailed Description

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Objective:

This project will study epigenetic mechanisms, the inheritance of (both Mendelian and complex) and biomarkers of Immune Mediated Eye Diseases, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when genetically mutated or epigenetically regulated, cause immune mediated eye disease, and the pathophysiology through which they act.

Study Population: The number of participants to be enrolled has no logical upper limit, but will be at 1,000 during the next five years. Race, age and sex matched controls, anonymous volunteers will also be needed to donate a blood sample. The study consists of ascertaining individuals and families with multiple individuals, if possible, affected by immune mediated ocular disease.

Design:

These patients and their families will undergo detailed ophthalmologic examinations and, where indicated, additional non-investigational examinations to characterize their ocular status. A blood sample will be collected from each individual and immunophenotyped using Flow Cytometry. Serum will be isolated for testing serological markers. One or more sub-populations of cells (including but not limited to CD4 plus and CD8 plus T cells, B cells, CD14 plus monocytes, dendritic cells, NK cells, neutrophils and granulocytes) will be isolated. DNA, RNA and chromatin may be isolated for further gene expression profiling and epigenetic studies. Association of genetic or epigenetic changes with ocular inflammatory disease in patients and their families will be identified using one of the techniques including but not limited to DNA-seq, BS-seq, MeDIP-seq, ChIP-seq, RNA-seq, microarray, PCR, and multicolor Flow Cytometry staining. DNA samples from the AREDS study, held under the DCR/NEI Repository protocol (07-EI-0168), will also be used for analysis. If necessary, the gene product or blood sample will be characterized biochemically.

Outcome Measures:

Immunophenotyping, gene expression and epigenetic changes will be reported using Statistical analysis performed using the t test or ANOVA and post-hoc testing with Fisher s least significant difference test. Unless otherwise noted, results are presented as the mean SEM. Biochemical, metabolic, and physiological effects will be individualized to the specific assay

Conditions

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Diabetic Retinopathy Age-Related Macular Degeneration (AMD) Uveitis

Keywords

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OCULAR INFLAMMATORY DISEASE Immune Mediated Gene Expression Patterns Diabetic Retinopathy Age-Related Macular Degeneration AMD Uveitis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Eligibility Criteria

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Inclusion Criteria

Participants with the following will be recruited:

* Individuals or family members of individuals with immune mediated retinal disorders, including uveitis, age related macular degeneration, and diabetic retinopathy.
* Adults must be capable of providing their own consent.
* All participants must be able to cooperate with study examination and phlebotomy.
* Children must be older than 4 years of age.

Exclusion Criteria

* Individuals with diseases, infections, or trauma that mimic immune medicated retinal disorders.
* Children requiring sedation for study procedures.
Minimum Eligible Age

4 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Eye Institute (NEI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hatice N Sen, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Eye Institute (NEI)

Locations

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National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

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United States

References

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Becker KG, Simon RM, Bailey-Wilson JE, Freidlin B, Biddison WE, McFarland HF, Trent JM. Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9979-84. doi: 10.1073/pnas.95.17.9979.

Reference Type BACKGROUND
PMID: 9707586 (View on PubMed)

Richardson B. Primer: epigenetics of autoimmunity. Nat Clin Pract Rheumatol. 2007 Sep;3(9):521-7. doi: 10.1038/ncprheum0573.

Reference Type BACKGROUND
PMID: 17762851 (View on PubMed)

Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005 Mar 17;434(7031):400-4. doi: 10.1038/nature03479.

Reference Type BACKGROUND
PMID: 15772666 (View on PubMed)

Other Identifiers

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08-EI-0099

Identifier Type: -

Identifier Source: secondary_id

080099

Identifier Type: -

Identifier Source: org_study_id